Difference between revisions of "Gastrointestinal stromal tumor"
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[[#top|Back to Top]] | [[#top|Back to Top]] | ||
</div> | </div> | ||
− | { | + | {{#lst:Editorial board transclusions|gist}} |
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''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Gastrointestinal stromal tumor - null regimens|this page]]. If you still can't find it, please let us know so we can add it!'' | ''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Gastrointestinal stromal tumor - null regimens|this page]]. If you still can't find it, please let us know so we can add it!'' | ||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
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{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
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=Guidelines= | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
==ESMO/EURACAN/GENTURIS== | ==ESMO/EURACAN/GENTURIS== | ||
− | *'''2021:''' Casali et al. [https://doi.org/10.1016/j.annonc.2021.09.005 Gastrointestinal stromal tumours: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up] | + | *'''2021:''' Casali et al. [https://doi.org/10.1016/j.annonc.2021.09.005 Gastrointestinal stromal tumours: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/34560242/ PubMed] |
− | + | **'''2018:''' Casali et al. [https://doi.org/10.1093/annonc/mdy095 Gastrointestinal stromal tumours: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/29846513/ PubMed] | |
− | + | **'''2014:''' [https://doi.org/10.1093/annonc/mdu255 Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/25210085/ PubMed] | |
− | *'''2018:''' Casali et al. [https:// | + | **'''2012:''' [https://doi.org/10.1093/annonc/mds252 Gastrointestinal stromal tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/22997454/ PubMed] |
− | *'''2014:''' [ | + | **'''2010:''' Casali & Blay. [https://doi.org/10.1093/annonc/mdq208 Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/20555113/ PubMed] |
+ | **'''2009:''' Casali et al. [https://doi.org/10.1093/annonc/mdp131 Gastrointestinal stromal tumours: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454466/ PubMed] | ||
+ | **'''2007:''' Blay & Le Cesne. [https://doi.org/10.1093/annonc/mdm024 Gastrointestinal stromal tumors: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/17491033/ PubMed] | ||
− | ==[https:// | + | ==French Intergroup== |
+ | *'''2019:''' Landi et al. [https://doi.org/10.1016/j.dld.2019.07.006 Gastrointestinal stromal tumours (GISTs): French Intergroup Clinical Practice Guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO)] [https://pubmed.ncbi.nlm.nih.gov/31387778/ PubMed] | ||
− | *[https://www.nccn.org/ | + | ==NCCN== |
+ | *[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1507 NCCN Guidelines - Gastrointestinal Stromal Tumors] | ||
+ | **'''2014:''' von Mehren et al. [https://doi.org/10.6004/jnccn.2014.0080 Gastrointestinal Stromal Tumors, Version 2.2014] [https://pubmed.ncbi.nlm.nih.gov/24925196/ PubMed] | ||
=Neoadjuvant therapy= | =Neoadjuvant therapy= | ||
==Imatinib monotherapy {{#subobject:abb5dd|Regimen=1}}== | ==Imatinib monotherapy {{#subobject:abb5dd|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:3b663c|Variant=1}}=== | ===Regimen {{#subobject:3b663c|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
Line 47: | Line 43: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
− | |||
*Kit (CD117) positive | *Kit (CD117) positive | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Imatinib (Gleevec)]] 600 mg PO once per day | *[[Imatinib (Gleevec)]] 600 mg PO once per day | ||
− | |||
'''28-day cycle for 2 to 3 cycles; stopped on the day prior to surgery''' | '''28-day cycle for 2 to 3 cycles; stopped on the day prior to surgery''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *[[Surgery#Surgical_resection|Surgery]], then adjuvant [[#Imatinib_monotherapy_2|imatinib]] x 2 y, resumed as soon as possible postoperatively | |
− | *[[Surgery#Surgical_resection|Surgery]], then [[#Imatinib_monotherapy_2|imatinib]] x 2 y, resumed as soon as possible postoperatively | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | + | #'''RTOG 0132:''' Eisenberg BL, Harris J, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M. Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol. 2009 Jan 1;99(1):42-7. [https://doi.org/10.1002/jso.21160 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606912/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18942073/ PubMed] | |
− | #'''RTOG 0132:''' Eisenberg BL, Harris J, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M. Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol. 2009 Jan 1;99(1):42-7. [https://doi.org/10.1002/jso.21160 link to original article] ''' | + | ##'''Update:''' Wang D, Zhang Q, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M, Eisenberg BL. Phase II trial of neoadjuvant/adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors: long-term follow-up results of Radiation Therapy Oncology Group 0132. Ann Surg Oncol. 2012 Apr;19(4):1074-80. Epub 2011 Dec 28. Erratum in: Ann Surg Oncol. 2012 Jul;19(7):2420. [https://doi.org/10.1245/s10434-011-2190-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800166/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22203182/ PubMed] |
− | ##'''Update:''' Wang D, Zhang Q, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M, Eisenberg BL. Phase II trial of neoadjuvant/adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors: long-term follow-up results of Radiation Therapy Oncology Group 0132. Ann Surg Oncol. 2012 Apr;19(4):1074-80. Epub 2011 Dec 28. Erratum in: Ann Surg Oncol. 2012 Jul;19(7):2420. [https://doi.org/10.1245/s10434-011-2190-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800166/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22203182 PubMed] | ||
− | |||
=Adjuvant therapy= | =Adjuvant therapy= | ||
==Imatinib monotherapy {{#subobject:32bd51|Regimen=1}}== | ==Imatinib monotherapy {{#subobject:32bd51|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, 12 months of treatment {{#subobject:90c752|Variant=1}}=== | ===Regimen variant #1, 12 months of treatment {{#subobject:90c752|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
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{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 82: | Line 75: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915459/ Dematteo et al. 2009 (ACOSOG Z9001)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915459/ Dematteo et al. 2009 (ACOSOG Z9001)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-204-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|2002-2007 | |2002-2007 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-esc) | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
|[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo|Placebo]] | |[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo|Placebo]] | ||
− | | style="background-color:#1a9850" |Superior RFS<br>RFS12: 98% vs 83%<br>(HR 0.35, 95% CI 0.22-0.53) | + | | style="background-color:#1a9850" |Superior RFS (primary endpoint)<br>RFS12: 98% vs 83%<br>(HR 0.35, 95% CI 0.22-0.53) |
|- | |- | ||
|[https://doi.org/10.1001/jama.2012.347 Joensuu et al. 2012 (SSG XVIII/AIO)] | |[https://doi.org/10.1001/jama.2012.347 Joensuu et al. 2012 (SSG XVIII/AIO)] | ||
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''<sup>1</sup>Reported efficacy for SSG XVIII/AIO is based on the 2020 update.''<br> | ''<sup>1</sup>Reported efficacy for SSG XVIII/AIO is based on the 2020 update.''<br> | ||
''Treatment is started within 12 weeks after surgery. While this is the FDA-recommended dose, it is noted that the optimal treatment duration is unknown.'' | ''Treatment is started within 12 weeks after surgery. While this is the FDA-recommended dose, it is noted that the optimal treatment duration is unknown.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
− | |||
*Kit (CD117) positive | *Kit (CD117) positive | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#Surgical_resection|Surgery]] | *[[Surgery#Surgical_resection|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Imatinib (Gleevec)]] 400 mg PO once per day | *[[Imatinib (Gleevec)]] 400 mg PO once per day | ||
− | |||
'''12-month course''' | '''12-month course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 2 years of treatment {{#subobject:3c163c|Variant=1}}=== | ===Regimen variant #2, 2 years of treatment {{#subobject:3c163c|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
Line 121: | Line 118: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
− | |||
*Kit (CD117) positive | *Kit (CD117) positive | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *Neoadjuvant [[#Imatinib_monotherapy|imatinib]], then [[Surgery#Surgical_resection|Surgery]] | |
− | *[[#Imatinib_monotherapy| | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Imatinib (Gleevec)]] 600 mg PO once per day | *[[Imatinib (Gleevec)]] 600 mg PO once per day | ||
− | |||
'''2-year course''' | '''2-year course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 3 years of treatment {{#subobject:238c82|Variant=1}}=== | ===Regimen variant #3, 3 years of treatment {{#subobject:238c82|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
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{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 148: | Line 145: | ||
|- | |- | ||
|[https://doi.org/10.1001/jama.2012.347 Joensuu et al. 2012 (SSG XVIII/AIO)] | |[https://doi.org/10.1001/jama.2012.347 Joensuu et al. 2012 (SSG XVIII/AIO)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-205-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|2004-2008 | |2004-2008 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-esc) | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
|[[#Imatinib_monotherapy_2|Imatinib]] x 12 mos | |[[#Imatinib_monotherapy_2|Imatinib]] x 12 mos | ||
− | | style="background-color:#1a9850" |Superior OS<sup>1</sup><br>(HR 0.55, 95% CI 0.37-0.83) | + | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (secondary endpoint)<br>OS120: 79% vs 65.3%<br>(HR 0.55, 95% CI 0.37-0.83)<br><br>Superior RFS (primary endpoint)<br>RFS60: 65.6% vs 47.9%<br>(HR 0.46, 95% CI 0.32-0.65) |
|- | |- | ||
|} | |} | ||
''<sup>1</sup>Reported efficacy is based on the 2020 update.''<br> | ''<sup>1</sup>Reported efficacy is based on the 2020 update.''<br> | ||
''Treatment is to be started within 12 weeks after surgery. While this is the FDA-recommended dose, it is noted that the optimal treatment duration is unknown.'' | ''Treatment is to be started within 12 weeks after surgery. While this is the FDA-recommended dose, it is noted that the optimal treatment duration is unknown.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
− | |||
*Kit (CD117) positive | *Kit (CD117) positive | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#Surgical_resection|Surgery]] | *[[Surgery#Surgical_resection|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Imatinib (Gleevec)]] 400 mg PO once per day | *[[Imatinib (Gleevec)]] 400 mg PO once per day | ||
− | |||
'''36-month course''' | '''36-month course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''RTOG 0132:''' Eisenberg BL, Harris J, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M. Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol. 2009 Jan 1;99(1):42-7. [https://doi.org/10.1002/jso.21160 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606912/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18942073/ PubMed] | |
− | #'''RTOG 0132:''' Eisenberg BL, Harris J, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M. Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol. 2009 Jan 1;99(1):42-7. [https://doi.org/10.1002/jso.21160 link to original article] ''' | + | ##'''Update:''' Wang D, Zhang Q, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M, Eisenberg BL. Phase II trial of neoadjuvant/adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors: long-term follow-up results of Radiation Therapy Oncology Group 0132. Ann Surg Oncol. 2012 Apr;19(4):1074-80. Epub 2011 Dec 28. Erratum in: Ann Surg Oncol. 2012 Jul;19(7):2420. [https://doi.org/10.1245/s10434-011-2190-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800166/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22203182/ PubMed] |
− | ##'''Update:''' Wang D, Zhang Q, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M, Eisenberg BL. Phase II trial of neoadjuvant/adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors: long-term follow-up results of Radiation Therapy Oncology Group 0132. Ann Surg Oncol. 2012 Apr;19(4):1074-80. Epub 2011 Dec 28. Erratum in: Ann Surg Oncol. 2012 Jul;19(7):2420. [https://doi.org/10.1245/s10434-011-2190-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800166/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22203182 PubMed] | + | #'''ACOSOG Z9001:''' Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K; American College of Surgeons Oncology Group. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Mar 28;373(9669):1097-104. Epub 2009 Mar 18. [https://doi.org/10.1016/S0140-6736(09)60500-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915459/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19303137/ PubMed] [https://clinicaltrials.gov/study/NCT00041197 NCT00041197] |
− | #'''ACOSOG Z9001:''' Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K; American College of Surgeons Oncology Group. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Mar 28;373(9669):1097-104. Epub 2009 Mar 18. [https:// | + | #'''SSG XVIII/AIO:''' Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schütte J, Ramadori G, Hohenberger P, Duyster J, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Sarlomo-Rikala M, Nilsson B, Sihto H, Monge OR, Bono P, Kallio R, Vehtari A, Leinonen M, Alvegård T, Reichardt P. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA. 2012 Mar 28;307(12):1265-72. [https://doi.org/10.1001/jama.2012.347 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22453568/ PubMed] [https://clinicaltrials.gov/study/NCT00116935 NCT00116935] |
− | #'''SSG XVIII/AIO:''' Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schütte J, Ramadori G, Hohenberger P, Duyster J, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Sarlomo-Rikala M, Nilsson B, Sihto H, Monge OR, Bono P, Kallio R, Vehtari A, Leinonen M, Alvegård T, Reichardt P. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA. 2012 Mar 28;307(12):1265-72. [https://doi.org/10.1001/jama.2012.347 link to original article] ''' | + | ##'''Update:''' Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hartmann JT, Pink D, Ramadori G, Hohenberger P, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Nilsson B, Sihto H, Bono P, Kallio R, Junnila J, Alvegård T, Reichardt P. Adjuvant imatinib for high-risk GI stromal tumor: analysis of a randomized trial. J Clin Oncol. 2016 Jan 20;34(3):244-50. Epub 2015 Nov 2. [https://doi.org/10.1200/JCO.2015.62.9170 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26527782/ PubMed] |
− | ##'''Update:''' Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hartmann JT, Pink D, Ramadori G, Hohenberger P, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Nilsson B, Sihto H, Bono P, Kallio R, Junnila J, Alvegård T, Reichardt P. Adjuvant imatinib for high-risk GI stromal tumor: analysis of a randomized trial. J Clin Oncol. 2016 Jan 20;34(3):244-50. Epub 2015 Nov 2. [https://doi.org/10.1200/JCO.2015.62.9170 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26527782 PubMed] | ||
## '''Update:''' Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hermes B, Schütte J, Cameron S, Hohenberger P, Jost PJ, Al-Batran SE, Lindner LH, Bauer S, Wardelmann E, Nilsson B, Kallio R, Jaakkola P, Junnila J, Alvegård T, Reichardt P. Survival Outcomes Associated With 3 Years vs 1 Year of Adjuvant Imatinib for Patients With High-Risk Gastrointestinal Stromal Tumors: An Analysis of a Randomized Clinical Trial After 10-Year Follow-up. JAMA Oncol. 2020 Aug 1;6(8):1241-1246. [https://doi.org/10.1001/jamaoncol.2020.2091 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260691/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32469385/ PubMed] | ## '''Update:''' Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hermes B, Schütte J, Cameron S, Hohenberger P, Jost PJ, Al-Batran SE, Lindner LH, Bauer S, Wardelmann E, Nilsson B, Kallio R, Jaakkola P, Junnila J, Alvegård T, Reichardt P. Survival Outcomes Associated With 3 Years vs 1 Year of Adjuvant Imatinib for Patients With High-Risk Gastrointestinal Stromal Tumors: An Analysis of a Randomized Clinical Trial After 10-Year Follow-up. JAMA Oncol. 2020 Aug 1;6(8):1241-1246. [https://doi.org/10.1001/jamaoncol.2020.2091 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260691/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32469385/ PubMed] | ||
+ | #'''IMADGIST:''' [https://clinicaltrials.gov/study/NCT02260505 NCT02260505] | ||
=Metastatic or unresectable disease, all lines of therapy= | =Metastatic or unresectable disease, all lines of therapy= | ||
− | |||
==Imatinib monotherapy {{#subobject:16a4ba|Regimen=1}}== | ==Imatinib monotherapy {{#subobject:16a4ba|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, standard-dose (400 mg/day) {{#subobject:58de4b|Variant=1}}=== | ===Regimen variant #1, standard-dose (400 mg/day) {{#subobject:58de4b|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 190: | Line 190: | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/nejmoa020461 Demetri et al. 2002] |
− | |2000-2001 | + | |2000-07 to 2001-04 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Imatinib_monotherapy_3|Imatinib]]; higher-dose (600 mg/day) | |[[#Imatinib_monotherapy_3|Imatinib]]; higher-dose (600 mg/day) | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/jco.2007.13.4452 Blanke et al. 2008 (SWOG S0033)] |
− | |2001-2002 | + | |2000-12-15 to 2001-09-01 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Imatinib_monotherapy_3|Imatinib]]; high-dose (800 mg/day) | ||
+ | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of PFS/OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(04)17098-0 Verweij et al. 2004 (EORTC 62005)] | ||
+ | |2001-02 to 2002-02 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Imatinib_monotherapy_3|Imatinib]]; high-dose | |[[#Imatinib_monotherapy_3|Imatinib]]; high-dose | ||
Line 210: | Line 216: | ||
|2002-2004 | |2002-2004 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |1. [[#Imatinib_monotherapy_3|Imatinib]] | + | |1. [[#Imatinib_monotherapy_3|Imatinib]] x 1 y<br>2. [[#Imatinib_monotherapy_3|Imatinib]] x 3 y |
| style="background-color:#1a9850" |Superior PFS | | style="background-color:#1a9850" |Superior PFS | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679092/ Blanke et al. 2015 (SWOG S0502)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679092/ Blanke et al. 2015 (SWOG S0502)] | ||
− | |2008-2009 | + | |2008-04-15 to 2009-10-01 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[#Imatinib_. | + | |[[#Imatinib_.26_Bevacizumab_999|Imatinib & Bevacizumab]] |
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
Line 222: | Line 228: | ||
|2009-2011 | |2009-2011 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[# | + | |[[#Nilotinib_monotherapy_999|Nilotinib]] |
| style="background-color:#1a9850" |Superior PFS | | style="background-color:#1a9850" |Superior PFS | ||
|- | |- | ||
Line 229: | Line 235: | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo_2|Placebo]] | |[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo_2|Placebo]] | ||
− | | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 1.8 vs 0.9 mo<br>(HR 0.46, 95% CI 0.27-0.76) | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 1.8 vs 0.9 mo<br>(HR 0.46, 95% CI 0.27-0.76) |
|- | |- | ||
|} | |} | ||
''<sup>1</sup>Reported efficacy for EORTC 62005 is based on the 2017 update.''<br> | ''<sup>1</sup>Reported efficacy for EORTC 62005 is based on the 2017 update.''<br> | ||
− | ''BFR14 had two separate comparisons, to one year and to three years of imatinib versus continuous (this arm); the efficacy outcome was the same in both reports.'' | + | ''Note: This arm of SWOG S0033 had pre-planned dose escalation to 800 mg/day at the time of progression. BFR14 had two separate comparisons, to one year and to three years of imatinib versus continuous (this arm); the efficacy outcome was the same in both reports.'' |
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Demetri et al. 2002 & SWOG S0033: Any number of prior chemotherapy regimens | ||
+ | *BFR14: None specified | ||
+ | *SWOG S0502 & ENESTg1: None allowed (untreated) | ||
+ | *RIGHT: Failure of imatinib & sunitinib | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Imatinib (Gleevec)]] 400 mg PO once per day | *[[Imatinib (Gleevec)]] 400 mg PO once per day | ||
− | + | '''Continued indefinitely (see note)''' | |
− | '''Continued indefinitely''' | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #2, higher-dose (600 mg/day) {{#subobject:304d2f|Variant=1}}=== | ===Regimen variant #2, higher-dose (600 mg/day) {{#subobject:304d2f|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/nejmoa020461 Demetri et al. 2002] |
− | |2000-2001 | + | |2000-07 to 2001-04 |
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[#Imatinib_monotherapy_3|Imatinib]]; standard-dose (400 mg/day) | |[[#Imatinib_monotherapy_3|Imatinib]]; standard-dose (400 mg/day) | ||
Line 255: | Line 268: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Demetri et al. 2002: Any number of prior chemotherapy regimens | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Imatinib (Gleevec)]] 600 mg PO once per day | *[[Imatinib (Gleevec)]] 600 mg PO once per day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, high-dose (800 mg/day) {{#subobject:4e83a6|Variant=1}}=== | ===Regimen variant #3, high-dose (800 mg/day) {{#subobject:4e83a6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 271: | Line 288: | ||
|[https://doi.org/10.1016/s0140-6736(01)06535-7 Van Oosterom et al. 2001] | |[https://doi.org/10.1016/s0140-6736(01)06535-7 Van Oosterom et al. 2001] | ||
|2000 | |2000 | ||
− | | style="background-color:#ffffbe" |Phase 1, | + | | style="background-color:#ffffbe" |Phase 1, fewer than 20 pts in this cohort |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0959-8049(02)00836-5 Verweij et al. 2003] |
− | | | + | |Not reported |
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/jco.2007.13.4452 Blanke et al. 2008 (SWOG S0033)] |
− | |2001-2002 | + | |2000-12-15 to 2001-09-01 |
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |[[#Imatinib_monotherapy_3|Imatinib]]; standard-dose with pre-planned dose-escalation at progression | ||
+ | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of PFS/OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(04)17098-0 Verweij et al. 2004 (EORTC 62005)] | ||
+ | |2001-02 to 2002-02 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-esc) | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
|[[#Imatinib_monotherapy_3|Imatinib]]; standard-dose | |[[#Imatinib_monotherapy_3|Imatinib]]; standard-dose | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<sup>1</sup> | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<sup>1</sup> | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679092/ Blanke et al. 2015 (SWOG S0502)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679092/ Blanke et al. 2015 (SWOG S0502)] | ||
− | |2008-2009 | + | |2008-04-15 to 2009-10-01 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[#Imatinib_. | + | |[[#Imatinib_.26_Bevacizumab_999|Imatinib & Bevacizumab]] |
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
Line 302: | Line 319: | ||
|2009-2011 | |2009-2011 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[# | + | |[[#Nilotinib_monotherapy_999|Nilotinib]] |
| style="background-color:#1a9850" |Superior PFS | | style="background-color:#1a9850" |Superior PFS | ||
|- | |- | ||
Line 308: | Line 325: | ||
''<sup>1</sup>Reported efficacy for EORTC 62005 is based on the 2017 update.''<br> | ''<sup>1</sup>Reported efficacy for EORTC 62005 is based on the 2017 update.''<br> | ||
''Note: this was the MTD in Van Oosterom et al. 2001. In some studies, high-dose imatinib was offered to patients with KIT exon 9 mutations in ENESTg1 and SWOG S0502; all other patients received standard-dose imatinib.'' | ''Note: this was the MTD in Van Oosterom et al. 2001. In some studies, high-dose imatinib was offered to patients with KIT exon 9 mutations in ENESTg1 and SWOG S0502; all other patients received standard-dose imatinib.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *SWOG S0033: Any number of prior chemotherapy regimens | ||
+ | *SWOG S0502 & ENESTg1: None allowed (untreated) | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Imatinib (Gleevec)]] 400 mg PO twice a day | *[[Imatinib (Gleevec)]] 400 mg PO twice a day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | + | #'''Phase 1:''' van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, Martens M, Webb A, Sciot R, Van Glabbeke M, Silberman S, Nielsen OS; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet. 2001 Oct 27;358(9291):1421-3. [https://doi.org/10.1016/s0140-6736(01)06535-7 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11705489/ PubMed] | |
− | #'''Phase 1:''' van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, Martens M, Webb A, Sciot R, Van Glabbeke M, Silberman S, Nielsen OS; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet. 2001 Oct 27;358(9291):1421-3. [https://doi.org/10.1016/s0140-6736(01)06535-7 link to original article] ''' | + | #Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002 Aug 15;347(7):472-80. [https://doi.org/10.1056/nejmoa020461 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12181401/ PubMed] |
− | #Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002 Aug 15;347(7):472-80. [https:// | + | #Verweij J, van Oosterom A, Blay JY, Judson I, Rodenhuis S, van der Graaf W, Radford J, Le Cesne A, Hogendoorn PC, di Paola ED, Brown M, Nielsen OS; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target: results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study. Eur J Cancer. 2003 Sep;39(14):2006-11. [https://doi.org/10.1016/S0959-8049(02)00836-5 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12957454/ PubMed] |
− | #Verweij J, van Oosterom A, Blay JY, Judson I, Rodenhuis S, van der Graaf W, Radford J, Le Cesne A, Hogendoorn PC, di Paola ED, Brown M, Nielsen OS; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target: results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study. Eur J Cancer. 2003 Sep;39(14):2006-11. [https:// | + | #'''EORTC 62005:''' Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, Issels R, van Oosterom A, Hogendoorn PC, Van Glabbeke M, Bertulli R, Judson I. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004 Sep 25-Oct 1;364(9440):1127-34. [https://doi.org/10.1016/S0140-6736(04)17098-0 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15451219/ PubMed] [https://clinicaltrials.gov/study/NCT00685828 NCT00685828] |
− | #'''EORTC 62005:''' Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, Issels R, van Oosterom A, Hogendoorn PC, Van Glabbeke M, Bertulli R, Judson I. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004 Sep 25-Oct 1;364(9440):1127-34. [https:// | + | ##'''Update:''' Zalcberg JR, Verweij J, Casali PG, Le Cesne A, Reichardt P, Blay JY, Schlemmer M, Van Glabbeke M, Brown M, Judson IR; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian Gastrointestinal Trials Group. Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg. Eur J Cancer. 2005 Aug;41(12):1751-7. [https://doi.org/10.1016/j.ejca.2005.04.034 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16098458/ PubMed] |
− | ##'''Update:''' Zalcberg JR, Verweij J, Casali PG, Le Cesne A, Reichardt P, Blay JY, Schlemmer M, Van Glabbeke M, Brown M, Judson IR; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian Gastrointestinal Trials Group. Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg. Eur J Cancer. 2005 Aug;41(12):1751-7. [https:// | + | ##'''Update:''' Casali PG, Zalcberg J, Le Cesne A, Reichardt P, Blay JY, Lindner LH, Judson IR, Schöffski P, Leyvraz S, Italiano A, Grünwald V, Pousa AL, Kotasek D, Sleijfer S, Kerst JM, Rutkowski P, Fumagalli E, Hogendoorn P, Litière S, Marreaud S, van der Graaf W, Gronchi A, Verweij J; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian Gastrointestinal Trials Group. Ten-year progression-free and overall survival in patients with unresectable or metastatic GI stromal tumors: long-term analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group intergroup phase III randomized trial on imatinib at two dose levels. J Clin Oncol. 2017 May 20;35(15):1713-1720. Epub 2017 Mar 31. [https://doi.org/10.1200/JCO.2016.71.0228 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28362562/ PubMed] |
− | ##'''Update:''' Casali PG, Zalcberg J, Le Cesne A, Reichardt P, Blay JY, Lindner LH, Judson IR, Schöffski P, Leyvraz S, Italiano A, Grünwald V, Pousa AL, Kotasek D, Sleijfer S, Kerst JM, Rutkowski P, Fumagalli E, Hogendoorn P, Litière S, Marreaud S, van der Graaf W, Gronchi A, Verweij J; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian Gastrointestinal Trials Group. Ten-year progression-free and overall survival in patients with unresectable or metastatic GI stromal tumors: long-term analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group intergroup phase III randomized trial on imatinib at two dose levels. J Clin Oncol. 2017 May 20;35(15):1713-1720. Epub 2017 Mar 31. [https://doi.org/10.1200/JCO.2016.71.0228 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28362562 PubMed] | + | #'''BFR14:''' Blay JY, Le Cesne A, Ray-Coquard I, Bui B, Duffaud F, Delbaldo C, Adenis A, Viens P, Rios M, Bompas E, Cupissol D, Guillemet C, Kerbrat P, Fayette J, Chabaud S, Berthaud P, Perol D; French Sarcoma Group. Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol. 2007 Mar 20;25(9):1107-13. [https://doi.org/10.1200/JCO.2006.09.0183 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17369574/ PubMed] [https://clinicaltrials.gov/study/NCT00367861 NCT00367861] |
− | #'''BFR14:''' Blay JY, Le Cesne A, Ray-Coquard I, Bui B, Duffaud F, Delbaldo C, Adenis A, Viens P, Rios M, Bompas E, Cupissol D, Guillemet C, Kerbrat P, Fayette J, Chabaud S, Berthaud P, Perol D; French Sarcoma Group. Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol. 2007 Mar 20;25(9):1107-13. [https://doi.org/10.1200/JCO.2006.09.0183 link to original article] ''' | + | ##'''Update:''' Le Cesne A, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Cioffi A, Emile JF, Chabaud S, Pérol D, Blay JY; French Sarcoma Group. Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol. 2010 Oct;11(10):942-9. Epub 2010 Sep 21. [https://doi.org/10.1016/S1470-2045(10)70222-9 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20864406/ PubMed] |
− | ##'''Update:''' Le Cesne A, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Cioffi A, Emile JF, Chabaud S, Pérol D, Blay JY; French Sarcoma Group. Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol. 2010 Oct;11(10):942-9. Epub 2010 Sep 21. [https:// | + | #'''SWOG S0033:''' Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, Raymond AK, Bramwell VH, Baker LH, Maki RG, Tanaka M, Hecht JR, Heinrich MC, Fletcher CD, Crowley JJ, Borden EC. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008 Feb 1;26(4):626-32. [https://doi.org/10.1200/jco.2007.13.4452 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18235122/ PubMed] [https://clinicaltrials.gov/study/NCT00009906 NCT00009906] |
− | #'''SWOG S0033:''' Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, Raymond AK, Bramwell VH, Baker LH, Maki RG, Tanaka M, Hecht JR, Heinrich MC, Fletcher CD, Crowley JJ, Borden EC. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008 Feb 1;26(4):626-32. [https://doi.org/10.1200/jco.2007.13.4452 link to original article] ''' | ||
##'''Update:''' Heinrich MC, Rankin C, Blanke CD, Demetri GD, Borden EC, Ryan CW, von Mehren M, Blackstein ME, Priebat DA, Tap WD, Maki RG, Corless CL, Fletcher JA, Owzar K, Crowley JJ, Benjamin RS, Baker LH. Correlation of Long-term Results of Imatinib in Advanced Gastrointestinal Stromal Tumors With Next-Generation Sequencing Results: Analysis of Phase 3 SWOG Intergroup Trial S0033. JAMA Oncol. 2017 Jul 1;3(7):944-952. Erratum in: JAMA Oncol. 2017 Jul 1;3(7):1002. [https://doi.org/10.1001/jamaoncol.2016.6728 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5727908/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28196207/ PubMed] | ##'''Update:''' Heinrich MC, Rankin C, Blanke CD, Demetri GD, Borden EC, Ryan CW, von Mehren M, Blackstein ME, Priebat DA, Tap WD, Maki RG, Corless CL, Fletcher JA, Owzar K, Crowley JJ, Benjamin RS, Baker LH. Correlation of Long-term Results of Imatinib in Advanced Gastrointestinal Stromal Tumors With Next-Generation Sequencing Results: Analysis of Phase 3 SWOG Intergroup Trial S0033. JAMA Oncol. 2017 Jul 1;3(7):944-952. Erratum in: JAMA Oncol. 2017 Jul 1;3(7):1002. [https://doi.org/10.1001/jamaoncol.2016.6728 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5727908/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28196207/ PubMed] | ||
− | #'''Meta-analysis:''' Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST). Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. J Clin Oncol. 2010 Mar 1;28(7):1247-53. Epub 2010 Feb 1. [https://doi.org/10.1200/jco.2009.24.2099 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834472/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20124181 PubMed] | + | #'''Meta-analysis:''' Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST). Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. J Clin Oncol. 2010 Mar 1;28(7):1247-53. Epub 2010 Feb 1. [https://doi.org/10.1200/jco.2009.24.2099 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834472/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20124181/ PubMed] |
− | #'''RIGHT:''' Kang YK, Ryu MH, Yoo C, Ryoo BY, Kim HJ, Lee JJ, Nam BH, Ramaiya N, Jagannathan J, Demetri GD. Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1175-82. Epub 2013 Oct 18. [https:// | + | #'''RIGHT:''' Kang YK, Ryu MH, Yoo C, Ryoo BY, Kim HJ, Lee JJ, Nam BH, Ramaiya N, Jagannathan J, Demetri GD. Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1175-82. Epub 2013 Oct 18. [https://doi.org/10.1016/S1470-2045(13)70453-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347867/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24140183/ PubMed] [https://clinicaltrials.gov/study/NCT01151852 NCT01151852] |
− | #'''ENESTg1:''' Blay JY, Shen L, Kang YK, Rutkowski P, Qin S, Nosov D, Wan D, Trent J, Srimuninnimit V, Pápai Z, Le Cesne A, Novick S, Taningco L, Mo S, Green S, Reichardt P, Demetri GD. Nilotinib versus imatinib as first-line therapy for patients with unresectable or metastatic gastrointestinal stromal tumours (ENESTg1): a randomised phase 3 trial. Lancet Oncol. 2015 May;16(5):550-60. Epub 2015 Apr 14. [https:// | + | #'''ENESTg1:''' Blay JY, Shen L, Kang YK, Rutkowski P, Qin S, Nosov D, Wan D, Trent J, Srimuninnimit V, Pápai Z, Le Cesne A, Novick S, Taningco L, Mo S, Green S, Reichardt P, Demetri GD. Nilotinib versus imatinib as first-line therapy for patients with unresectable or metastatic gastrointestinal stromal tumours (ENESTg1): a randomised phase 3 trial. Lancet Oncol. 2015 May;16(5):550-60. Epub 2015 Apr 14. [https://doi.org/10.1016/S1470-2045(15)70105-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521211/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25882987/ PubMed] [https://clinicaltrials.gov/study/NCT00785785 NCT00785785] |
− | #'''SWOG S0502:''' Blanke CD, Rankin C, Corless C, Eary JF, Mulder K, Okuno SH, George S, Heinrich M. S0502: A SWOG phase III randomized study of imatinib, with or without bevacizumab, in patients with untreated metastatic or unresectable gastrointestinal stromal tumors. Oncologist. 2015 Dec;20(12):1353-4. Epub 2015 Nov 17. [https://doi.org/10.1634/theoncologist.2015-0295 link to original article] ''' | + | #'''SWOG S0502:''' Blanke CD, Rankin C, Corless C, Eary JF, Mulder K, Okuno SH, George S, Heinrich M. S0502: A SWOG phase III randomized study of imatinib, with or without bevacizumab, in patients with untreated metastatic or unresectable gastrointestinal stromal tumors. Oncologist. 2015 Dec;20(12):1353-4. Epub 2015 Nov 17. [https://doi.org/10.1634/theoncologist.2015-0295 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679092/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26576593/ PubMed] [https://clinicaltrials.gov/study/NCT00324987 NCT00324987] |
=Metastatic or unresectable disease, second-line= | =Metastatic or unresectable disease, second-line= | ||
''Most trials define this context as imatinib-resistant.'' | ''Most trials define this context as imatinib-resistant.'' | ||
==Linsitinib monotherapy {{#subobject:cfbaff|Regimen=1}}== | ==Linsitinib monotherapy {{#subobject:cfbaff|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:1debcd|Variant=1}}=== | ===Regimen {{#subobject:1debcd|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
! style="width: 33%" |Study | ! style="width: 33%" |Study | ||
− | ! style="width: 33%" | | + | ! style="width: 33%" |Dates of enrollment |
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
Line 375: | Line 365: | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|} | |} | ||
− | ''Patients in this study had wild-type GIST and had previously failed treatment with at least one prior TKI'' | + | ''Patients in this study had wild-type GIST and had previously failed treatment with at least one prior TKI'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Linsitinib (OSI-906)]] 150 mg PO twice per day on days 1 to 28 | |
− | *[[Linsitinib (OSI-906)]] 150 mg PO twice per day | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''SARC 022:''' Von Mehren M, George S, Heinrich M, Schuetze S, Yap J, Yu J, Abbott A, Litwin S, Crowley J, Belinsky M, Janeway K, Hornick J, Flieder D, Chugh R, Rink L, Van den Abbeele A. Linsitinib (OSI-906) for the Treatment of Adult and Pediatric Wild-Type Gastrointestinal Stromal Tumors: a SARC Phase II Study. Clin Cancer Res. 2020 April; 15;26(8):1837-1845. Epub 2019 Dec 2. [https://clincancerres.aacrjournals.org/content/26/8/1837.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7856429/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31792037/ PubMed] [https://clinicaltrials.gov/study/NCT01560260 NCT01560260] | |
− | #'''SARC 022:''' Von Mehren M, George S, Heinrich M, Schuetze S, Yap J, Yu J, Abbott A, Litwin S, Crowley J, Belinsky M, Janeway K, Hornick J, Flieder D, Chugh R, Rink L, Van den Abbeele A. Linsitinib (OSI-906) for the Treatment of Adult and Pediatric Wild-Type Gastrointestinal Stromal Tumors: a SARC Phase II Study. Clin Cancer Res. 2020 April; 15;26(8):1837-1845. Epub 2019 Dec 2. [https://clincancerres.aacrjournals.org/content/26/8/1837.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7856429/ link to PMC article] ''' | ||
==Sunitinib monotherapy {{#subobject:ec3261|Regimen=1}}== | ==Sunitinib monotherapy {{#subobject:ec3261|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:38e8e3|Variant=1}}=== | ===Regimen {{#subobject:38e8e3|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(06)69446-4 Demetri et al. 2006 (A6181004)] |
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-199-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|2003-2005 | |2003-2005 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-esc) | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
|[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo_2|Placebo]] | |[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo_2|Placebo]] | ||
− | | style="background-color:#1a9850" |Superior TTP<br>Median TTP: 27.3 vs 6.4 weeks<br>(HR 0.33) | + | | style="background-color:#1a9850" |Superior TTP (primary endpoint)<br>Median TTP: 27.3 vs 6.4 weeks<br>(HR 0.33) |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143095/ Adenis et al. 2014 (AB07001)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143095/ Adenis et al. 2014 (AB07001)] | ||
|2009-2011 | |2009-2011 | ||
| style="background-color:#1a9851" |Randomized Phase 2 (C) | | style="background-color:#1a9851" |Randomized Phase 2 (C) | ||
− | |[[# | + | |[[#Masitinib_monotherapy_777|Masitinib]] |
| style="background-color:#fc8d59" |Seems to have inferior OS | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746771/ Bauer et al. 2022 (INTRIGUE)] | ||
+ | |2019 to not reported | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Ripretinib_monotherapy_999|Ripretinib]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 8.3 vs 8 mo<br>(HR 0.95, 95% CI 0.75-1.22) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *A6181004, AB07001, INTRIGUE: Failure of imatinib | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Sunitinib (Sutent)]] 50 mg PO once per day on days 1 to 28 | *[[Sunitinib (Sutent)]] 50 mg PO once per day on days 1 to 28 | ||
− | |||
− | |||
'''42-day cycles''' | '''42-day cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *[[Sunitinib (Sutent)]] dose may be decreased to 37.5 mg once per day or 25 mg once per day depending on tolerability | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''A6181004:''' Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. [https://doi.org/10.1016/S0140-6736(06)69446-4 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17046465/ PubMed] [https://clinicaltrials.gov/study/NCT00075218 NCT00075218] | |
− | #'''A6181004:''' Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. [https:// | + | ##'''Update:''' Demetri GD, Garrett CR, Schöffski P, Shah MH, Verweij J, Leyvraz S, Hurwitz HI, Pousa AL, Le Cesne A, Goldstein D, Paz-Ares L, Blay JY, McArthur GA, Xu QC, Huang X, Harmon CS, Tassell V, Cohen DP, Casali PG. Complete longitudinal analyses of the randomized, placebo-controlled, phase III trial of sunitinib in patients with gastrointestinal stromal tumor following imatinib failure. Clin Cancer Res. 2012 Jun 1;18(11):3170-9. [https://clincancerres.aacrjournals.org/content/18/11/3170.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030710/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22661587/ PubMed] |
− | ##'''Update:''' Demetri GD, Garrett CR, Schöffski P, Shah MH, Verweij J, Leyvraz S, Hurwitz HI, Pousa AL, Le Cesne A, Goldstein D, Paz-Ares L, Blay JY, McArthur GA, Xu QC, Huang X, Harmon CS, Tassell V, Cohen DP, Casali PG. Complete longitudinal analyses of the randomized, placebo-controlled, phase III trial of sunitinib in patients with gastrointestinal stromal tumor following imatinib failure. Clin Cancer Res. 2012 Jun 1;18(11):3170-9. [https://clincancerres.aacrjournals.org/content/18/11/3170.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030710/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22661587 PubMed] | + | #'''AB07001:''' Adenis A, Blay JY, Bui-Nguyen B, Bouché O, Bertucci F, Isambert N, Bompas E, Chaigneau L, Domont J, Ray-Coquard I, Blésius A, Van Tine BA, Bulusu VR, Dubreuil P, Mansfield CD, Acin Y, Moussy A, Hermine O, Le Cesne A. Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial. Ann Oncol. 2014 Sep;25(9):1762-9. Epub 2014 Jul 25. [https://doi.org/10.1093/annonc/mdu237 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143095/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25122671/ PubMed] [https://clinicaltrials.gov/study/NCT01506336 NCT01506336] |
− | #'''AB07001:''' Adenis A, Blay JY, Bui-Nguyen B, Bouché O, Bertucci F, Isambert N, Bompas E, Chaigneau L, Domont J, Ray-Coquard I, Blésius A, Van Tine BA, Bulusu VR, Dubreuil P, Mansfield CD, Acin Y, Moussy A, Hermine O, Le Cesne A. Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial. Ann Oncol. 2014 Sep;25(9):1762-9. Epub 2014 Jul 25. [https://doi.org/10.1093/annonc/mdu237 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143095/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25122671 PubMed] NCT01506336 | + | #'''INTRIGUE:''' Bauer S, Jones RL, Blay JY, Gelderblom H, George S, Schöffski P, von Mehren M, Zalcberg JR, Kang YK, Razak AA, Trent J, Attia S, Le Cesne A, Su Y, Meade J, Wang T, Sherman ML, Ruiz-Soto R, Heinrich MC. Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Dec 1;40(34):3918-3928. Epub 2022 Aug 10. [https://doi.org/10.1200/jco.22.00294 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746771/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35947817/ PubMed] [https://clinicaltrials.gov/study/NCT03673501 NCT03673501] |
− | #'''AB11002:''' NCT01694277 | + | #'''AB11002:''' [https://clinicaltrials.gov/study/NCT01694277 NCT01694277] |
=Metastatic or unresectable disease, third-line= | =Metastatic or unresectable disease, third-line= | ||
− | |||
==Cabozantinib monotherapy {{#subobject:s9nxm1|Regimen=1}}== | ==Cabozantinib monotherapy {{#subobject:s9nxm1|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:8c0u8g|Variant=1}}=== | ===Regimen {{#subobject:8c0u8g|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
Line 440: | Line 441: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *CaboGIST: Failure of imatinib and sunitinib | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Cabozantinib (Cometriq)]] 60 mg PO once per day | + | *[[Cabozantinib (Cometriq)]] 60 mg PO once per day on days 1 to 28 |
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | #'''CaboGIST:''' Schöffski P, Mir O, Kasper B, Papai Z, Blay JY, Italiano A, Benson C, Kopeckova K, Ali N, Dileo P, LeCesne A, Menge F, Cousin S, Wardelmann E, Wozniak A, Marreaud S, Litiere S, Zaffaroni F, Nzokirantevye A, Vanden Bempt I, Gelderblom H. Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 'CaboGIST'. Eur J Cancer. 2020 Jul;134:62-74. Epub 2020 May 26. [https://doi.org/10.1016/j.ejca.2020.04.021 link to original article] ''' | + | #'''CaboGIST:''' Schöffski P, Mir O, Kasper B, Papai Z, Blay JY, Italiano A, Benson C, Kopeckova K, Ali N, Dileo P, LeCesne A, Menge F, Cousin S, Wardelmann E, Wozniak A, Marreaud S, Litiere S, Zaffaroni F, Nzokirantevye A, Vanden Bempt I, Gelderblom H. Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 'CaboGIST'. Eur J Cancer. 2020 Jul;134:62-74. Epub 2020 May 26. [https://doi.org/10.1016/j.ejca.2020.04.021 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32470848/ PubMed] [https://clinicaltrials.gov/study/NCT02216578 NCT02216578] |
− | |||
==Pazopanib monotherapy {{#subobject:cfbaff|Regimen=1}}== | ==Pazopanib monotherapy {{#subobject:cfbaff|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:1debcd|Variant=1}}=== | ===Regimen {{#subobject:1debcd|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(16)00075-9 Mir et al. 2016 (PAZOGIST)] |
|2011-2013 | |2011-2013 | ||
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc) | | style="background-color:#1a9851" |Randomized Phase 2 (E-esc) | ||
|[[Gastrointestinal_stromal_tumor_-_null_regimens#Best_supportive_care|Best supportive care]] | |[[Gastrointestinal_stromal_tumor_-_null_regimens#Best_supportive_care|Best supportive care]] | ||
− | | style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 3.4 vs 2.3 mo<br>(HR 0.59, 95% CI 0.37-0.96) | + | | style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 3.4 vs 2.3 mo<br>(HR 0.59, 95% CI 0.37-0.96) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *PAZOGIST: Failure of imatinib and sunitinib | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Pazopanib (Votrient)]] 800 mg PO once per day on days 1 to 28 | |
− | *[[Pazopanib (Votrient)]] 800 mg PO once per day | + | '''28-day cycles''' |
− | + | </div></div> | |
− | ''' | ||
===References=== | ===References=== | ||
− | + | #'''PAZOGIST:''' Mir O, Cropet C, Toulmonde M, Cesne AL, Molimard M, Bompas E, Cassier P, Ray-Coquard I, Rios M, Adenis A, Italiano A, Bouché O, Chauzit E, Duffaud F, Bertucci F, Isambert N, Gautier J, Blay JY, Pérol D; PAZOGIST study group of the French Sarcoma Groupe-Groupe d'Etude des Tumeurs Osseuses (GSF-GETO). Pazopanib plus best supportive care versus best supportive care alone in advanced gastrointestinal stromal tumours resistant to imatinib and sunitinib (PAZOGIST): a randomised, multicentre, open-label phase 2 trial. Lancet Oncol. 2016 May;17(5):632-41. Epub 2016 Apr 5. [https://doi.org/10.1016/S1470-2045(16)00075-9 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27068858/ PubMed] [https://clinicaltrials.gov/study/NCT01323400 NCT01323400] | |
− | #'''PAZOGIST:''' Mir O, Cropet C, Toulmonde M, Cesne AL, Molimard M, Bompas E, Cassier P, Ray-Coquard I, Rios M, Adenis A, Italiano A, Bouché O, Chauzit E, Duffaud F, Bertucci F, Isambert N, Gautier J, Blay JY, Pérol D; PAZOGIST study group of the French Sarcoma Groupe-Groupe d'Etude des Tumeurs Osseuses (GSF-GETO). Pazopanib plus best supportive care versus best supportive care alone in advanced gastrointestinal stromal tumours resistant to imatinib and sunitinib (PAZOGIST): a randomised, multicentre, open-label phase 2 trial. Lancet Oncol. 2016 May;17(5):632-41. Epub 2016 Apr 5. [https:// | ||
− | |||
==Regorafenib monotherapy {{#subobject:bd09ce|Regimen=1}}== | ==Regorafenib monotherapy {{#subobject:bd09ce|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:6dcadc|Variant=1}}=== | ===Regimen {{#subobject:6dcadc|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 488: | Line 492: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819942/ Demetri et al. 2012 (GRID)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819942/ Demetri et al. 2012 (GRID)] | ||
− | |2011 | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-200-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2011-01 to 2011-08 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-esc) | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
|[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo_2|Placebo]] | |[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo_2|Placebo]] | ||
− | | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 4.8 vs 0.9 mo<br>(HR 0.27, 95% CI 0.19-0.39) | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 4.8 vs 0.9 mo<br>(HR 0.27, 95% CI 0.19-0.39) |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478403/ Kang et al. 2021 (VOYAGER)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478403/ Kang et al. 2021 (VOYAGER)] | ||
− | |2018-2019 | + | |2018-03-26 to 2019-11-15 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[# | + | |[[#Avapritinib_monotherapy_999|Avapritinib]] |
| style="background-color:#d9ef8b" |Might have superior PFS<br>Median PFS: 5.6 vs 4.2 mo<br>(HR 0.80, 95% CI 0.64-1.01) | | style="background-color:#d9ef8b" |Might have superior PFS<br>Median PFS: 5.6 vs 4.2 mo<br>(HR 0.80, 95% CI 0.64-1.01) | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Prior treatment criteria==== | ||
+ | *GRID: Failure of imatinib & sunitinib | ||
+ | *VOYAGER: Failure of imatinib and one or two additional TKIs | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21 | *[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''GRID:''' Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Schöffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG; GRID study investigators. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):295-302. Epub 2012 Nov 22. [https://doi.org/10.1016/s0140-6736(12)61857-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819942/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23177515/ PubMed] [https://clinicaltrials.gov/study/NCT01271712 NCT01271712] | |
− | #'''GRID:''' Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Schöffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG; GRID study investigators. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):295-302. Epub 2012 Nov 22. [https://doi.org/10.1016/s0140-6736(12)61857-1 link to original article] ''' | + | #'''VOYAGER:''' Kang YK, George S, Jones RL, Rutkowski P, Shen L, Mir O, Patel S, Zhou Y, von Mehren M, Hohenberger P, Villalobos V, Brahmi M, Tap WD, Trent J, Pantaleo MA, Schöffski P, He K, Hew P, Newberry K, Roche M, Heinrich MC, Bauer S. Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study. J Clin Oncol. 2021 Oct 1;39(28):3128-3139. Epub 2021 Aug 3. [https://doi.org/10.1200/jco.21.00217 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478403/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34343033/ PubMed] [https://clinicaltrials.gov/study/NCT03465722 NCT03465722] |
− | #'''VOYAGER:''' Kang YK, George S, Jones RL, Rutkowski P, Shen L, Mir O, Patel S, Zhou Y, von Mehren M, Hohenberger P, Villalobos V, Brahmi M, Tap WD, Trent J, Pantaleo MA, Schöffski P, He K, Hew P, Newberry K, Roche M, Heinrich MC, Bauer S. Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study. J Clin Oncol. 2021 Oct 1;39(28):3128-3139. Epub 2021 Aug 3. [https://doi.org/10.1200/jco.21.00217 link to original article] ''' | ||
==Sorafenib monotherapy {{#subobject:ec8ga1|Regimen=1}}== | ==Sorafenib monotherapy {{#subobject:ec8ga1|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:381ibg3|Variant=1}}=== | ===Regimen {{#subobject:381ibg3|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
|[https://doi.org/10.1007/s10637-012-9795-9 Park et al. 2012 (SMC 2009-08-102)] | |[https://doi.org/10.1007/s10637-012-9795-9 Park et al. 2012 (SMC 2009-08-102)] | ||
Line 530: | Line 536: | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Prior treatment criteria==== | ||
+ | *SMC 2009-08-102: Failure of 2 or more TKIs | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day | *[[Sorafenib (Nexavar)]] 400 mg PO twice per day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''Abstract:''' Kindler HL, Campbell NP, Wroblewski K, Maki RG, D’Adamo DR, Chow WA, Gandara DR, Antonescu C, Stadler WM, Vokes EE. Sorafenib (SOR) in patients (pts) with imatinib (IM) and sunitinib (SU)-resistant (RES) gastrointestinal stromal tumors (GIST): Final results of a University of Chicago Phase II Consortium trial. 2011. 29 (15_suppl) 10009-10009. [https://doi.org/10.1200/jco.2011.29.15_suppl.10009 link to original article (abstract only)] | #'''Abstract:''' Kindler HL, Campbell NP, Wroblewski K, Maki RG, D’Adamo DR, Chow WA, Gandara DR, Antonescu C, Stadler WM, Vokes EE. Sorafenib (SOR) in patients (pts) with imatinib (IM) and sunitinib (SU)-resistant (RES) gastrointestinal stromal tumors (GIST): Final results of a University of Chicago Phase II Consortium trial. 2011. 29 (15_suppl) 10009-10009. [https://doi.org/10.1200/jco.2011.29.15_suppl.10009 link to original article (abstract only)] | ||
− | #'''SMC 2009-08-102:''' Park SH, Ryu MH, Ryoo BY, Im SA, Kwon HC, Lee SS, Park SR, Kang BY, Kang YK; Korean gastrointestinal stromal tumors study group. Sorafenib in patients with metastatic gastrointestinal stromal tumors who failed two or more prior tyrosine kinase inhibitors: a phase II study of Korean gastrointestinal stromal tumors study group. Invest New Drugs. 2012 Dec; 30(6) 2377-83. Epub 2012 Jan 25. [https://doi.org/10.1007/s10637-012-9795-9 link to original article] ''' | + | #'''SMC 2009-08-102:''' Park SH, Ryu MH, Ryoo BY, Im SA, Kwon HC, Lee SS, Park SR, Kang BY, Kang YK; Korean gastrointestinal stromal tumors study group. Sorafenib in patients with metastatic gastrointestinal stromal tumors who failed two or more prior tyrosine kinase inhibitors: a phase II study of Korean gastrointestinal stromal tumors study group. Invest New Drugs. 2012 Dec; 30(6) 2377-83. Epub 2012 Jan 25. [https://doi.org/10.1007/s10637-012-9795-9 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22270258/ PubMed] [https://clinicaltrials.gov/study/NCT01091207 NCT01091207] |
=Metastatic or unresectable disease, fourth-line= | =Metastatic or unresectable disease, fourth-line= | ||
''Many trials define this context as imatinib-, sunitinib-, and regorafenib-resistant.'' | ''Many trials define this context as imatinib-, sunitinib-, and regorafenib-resistant.'' | ||
==Avapritinib monotherapy {{#subobject:16ab1a|Regimen=1}}== | ==Avapritinib monotherapy {{#subobject:16ab1a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:q8bx4b|Variant=1}}=== | ===Regimen {{#subobject:q8bx4b|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 552: | Line 559: | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1016/s1470-2045(20)30269-2 Heinrich et al. 2020 (NAVIGATOR)] | |[https://doi.org/10.1016/s1470-2045(20)30269-2 Heinrich et al. 2020 (NAVIGATOR)] | ||
− | |2015-2018 | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-211-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2015-10-26 to 2018-11-16 | ||
| style="background-color:#ffffbe" |Phase 1 (RT) | | style="background-color:#ffffbe" |Phase 1 (RT) | ||
|} | |} | ||
− | ''Note: Patients in this study either | + | ''Note: Patients enrolled in this study met either the biomarker eligibility OR the prior treatment criteria. This is the recommended phase 2 dose.'' |
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Treatment failure with imatinib and at least 1 additional tyrosine kinase inhibitor | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
− | |||
*Gene: PDGFRA | *Gene: PDGFRA | ||
*Alteration: D842V | *Alteration: D842V | ||
− | + | </div> | |
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | [[Avapritinib (Ayvakit)]] 300 mg PO once per day on an empty stomach (at least 1 hour before and 2 hours after a meal) | + | ====Targeted therapy==== |
− | + | *[[Avapritinib (Ayvakit)]] 300 mg PO once per day, taken on an empty stomach (at least 1 hour before and 2 hours after a meal) | |
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | |||
<!-- #'''Abstract:''' Heinrich MC, Jones RL, Von Mehren M, Bauer S, Kang YK, Schoffski P, Eskens F, Mir O, Cassier PA, Serrano C, Tap WD, Trent JC, Rutkowski P, Patel S, Chawla SP, Meiri E, Zhou T, Mamlouk KK, Roche M, George S. Clinical activity of avapritinib in ≥ fourth-line (4L+) and PDGFRA Exon 18 gastrointestinal stromal tumors (GIST). J Clin Oncol. 2019 May 20. [https://doi.org/10.1200/JCO.2019.37.15_suppl.11022 link to abstract] --> | <!-- #'''Abstract:''' Heinrich MC, Jones RL, Von Mehren M, Bauer S, Kang YK, Schoffski P, Eskens F, Mir O, Cassier PA, Serrano C, Tap WD, Trent JC, Rutkowski P, Patel S, Chawla SP, Meiri E, Zhou T, Mamlouk KK, Roche M, George S. Clinical activity of avapritinib in ≥ fourth-line (4L+) and PDGFRA Exon 18 gastrointestinal stromal tumors (GIST). J Clin Oncol. 2019 May 20. [https://doi.org/10.1200/JCO.2019.37.15_suppl.11022 link to abstract] --> | ||
− | #'''NAVIGATOR:''' Heinrich MC, Jones RL, von Mehren M, Schöffski P, Serrano C, Kang YK, Cassier PA, Mir O, Eskens F, Tap WD, Rutkowski P, Chawla SP, Trent J, Tugnait M, Evans EK, Lauz T, Zhou T, Roche M, Wolf BB, Bauer S, George S. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020 Jul;21(7):935-946. Erratum in: Lancet Oncol. 2020 Sep;21(9):e418. [https://doi.org/10.1016/s1470-2045(20)30269-2 link to original article] ''' | + | #'''NAVIGATOR:''' Heinrich MC, Jones RL, von Mehren M, Schöffski P, Serrano C, Kang YK, Cassier PA, Mir O, Eskens F, Tap WD, Rutkowski P, Chawla SP, Trent J, Tugnait M, Evans EK, Lauz T, Zhou T, Roche M, Wolf BB, Bauer S, George S. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020 Jul;21(7):935-946. Erratum in: Lancet Oncol. 2020 Sep;21(9):e418. [https://doi.org/10.1016/s1470-2045(20)30269-2 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32615108/ PubMed] [https://clinicaltrials.gov/study/NCT02508532 NCT02508532] |
− | ##'''Update:''' Jones RL, Serrano C, von Mehren M, George S, Heinrich MC, Kang YK, Schöffski P, Cassier PA, Mir O, Chawla SP, Eskens FALM, Rutkowski P, Tap WD, Zhou T, Roche M, Bauer S. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. Eur J Cancer. 2021 Mar;145:132-142. Epub 2021 Jan 16. [https://doi.org/10.1016/j.ejca.2020.12.008 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33465704/ PubMed] | + | ##'''Update:''' Jones RL, Serrano C, von Mehren M, George S, Heinrich MC, Kang YK, Schöffski P, Cassier PA, Mir O, Chawla SP, Eskens FALM, Rutkowski P, Tap WD, Zhou T, Roche M, Bauer S. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. Eur J Cancer. 2021 Mar;145:132-142. Epub 2021 Jan 16. [https://doi.org/10.1016/j.ejca.2020.12.008 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9518931/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33465704/ PubMed] |
+ | ==Pimitespib monotherapy {{#subobject:bhg1ve|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:6huqrc|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.annonc.2022.05.518 Kurokawa et al. 2022 (CHAPTER-GIST-301)] | ||
+ | |2018-2020 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo_2|Placebo]] | ||
+ | | style="background-color:#1a9850" |Superior OS (secondary endpoint)<br>Median OS: 13.8 vs 7.6 mo<br>(HR 0.42, 95% CI 0.21-0.85) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *CHAPTER-GIST-301: Failure of imatinib, sunitinib, and regorafenib | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pimitespib (Jeselhy)]] 160 mg PO once per day on days 1 to 5, 8 to 12, 15 to 19 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''CHAPTER-GIST-301:''' Kurokawa Y, Honma Y, Sawaki A, Naito Y, Iwagami S, Komatsu Y, Takahashi T, Nishida T, Doi T. Pimitespib in patients with advanced gastrointestinal stromal tumor (CHAPTER-GIST-301): a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol. 2022 Sep;33(9):959-967. Epub 2022 Jun 8. [https://doi.org/10.1016/j.annonc.2022.05.518 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35688358/ PubMed] JapicCTI-184094 | ||
==Ripretinib monotherapy {{#subobject:bd11ce|Regimen=1}}== | ==Ripretinib monotherapy {{#subobject:bd11ce|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:6dugic|Variant=1}}=== | ===Regimen {{#subobject:6dugic|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 586: | Line 626: | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8383051/ Blay et al. 2020 (INVICTUS)] |
− | |2018 | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-228-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2018-02-27 to 2018-11-16 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-esc) | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
|[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo_2|Placebo]] | |[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo_2|Placebo]] | ||
− | | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 1 mo<br>(HR 0.15, 95% CI 0.09-0.25) | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 6.3 vs 1 mo<br>(HR 0.15, 95% CI 0.09-0.25) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Failure of imatinib, sunitinib, and regorafenib | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Ripretinib (Qinlock)]] 150 mg PO once per day | *[[Ripretinib (Qinlock)]] 150 mg PO once per day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''INVICTUS:''' Blay JY, Serrano C, Heinrich MC, Zalcberg J, Bauer S, Gelderblom H, Schöffski P, Jones RL, Attia S, D'Amato G, Chi P, Reichardt P, Meade J, Shi K, Ruiz-Soto R, George S, von Mehren M. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jul;21(7):923-934. Epub 2020 Jun 5. Erratum in: Lancet Oncol. 2020 Jul;21(7):e341. [https://doi.org/10.1016/s1470-2045(20)30168-6 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8383051/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32511981/ PubMed] [https://clinicaltrials.gov/study/NCT03353753 NCT03353753] | |
− | #'''INVICTUS:''' Blay JY, Serrano C, Heinrich MC, Zalcberg J, Bauer S, Gelderblom H, Schöffski P, Jones RL, Attia S, D'Amato G, Chi P, Reichardt P, Meade J, Shi K, Ruiz-Soto R, George S, von Mehren M. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jul;21(7):923-934. Epub 2020 Jun 5. Erratum in: Lancet Oncol. 2020 Jul;21(7):e341. [https://doi.org/10.1016/s1470-2045(20)30168-6 link to original article] ''' | ||
− | |||
[[Category:Gastrointestinal stromal tumor regimens]] | [[Category:Gastrointestinal stromal tumor regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Soft tissue sarcomas]] | [[Category:Soft tissue sarcomas]] | ||
[[Category:Gastrointestinal cancers]] | [[Category:Gastrointestinal cancers]] |
Latest revision as of 23:38, 15 July 2024
Page editor | Section editor | ||
---|---|---|---|
Eric I. Marks, MD Boston University Boston, MA, USA |
Elizabeth J. Davis, MD Vanderbilt University Nashville, TN, USA |
Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
11 regimens on this page
15 variants on this page
|
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ESMO/EURACAN/GENTURIS
- 2021: Casali et al. Gastrointestinal stromal tumours: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2018: Casali et al. Gastrointestinal stromal tumours: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2014: Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2012: Gastrointestinal stromal tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Casali & Blay. Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Casali et al. Gastrointestinal stromal tumours: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2007: Blay & Le Cesne. Gastrointestinal stromal tumors: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
French Intergroup
- 2019: Landi et al. Gastrointestinal stromal tumours (GISTs): French Intergroup Clinical Practice Guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO) PubMed
NCCN
- NCCN Guidelines - Gastrointestinal Stromal Tumors
- 2014: von Mehren et al. Gastrointestinal Stromal Tumors, Version 2.2014 PubMed
Neoadjuvant therapy
Imatinib monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Eisenberg et al. 2009 (RTOG 0132) | 2002-2006 | Phase 2 |
Biomarker eligibility criteria
- Kit (CD117) positive
Targeted therapy
- Imatinib (Gleevec) 600 mg PO once per day
28-day cycle for 2 to 3 cycles; stopped on the day prior to surgery
References
- RTOG 0132: Eisenberg BL, Harris J, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M. Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol. 2009 Jan 1;99(1):42-7. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- Update: Wang D, Zhang Q, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M, Eisenberg BL. Phase II trial of neoadjuvant/adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors: long-term follow-up results of Radiation Therapy Oncology Group 0132. Ann Surg Oncol. 2012 Apr;19(4):1074-80. Epub 2011 Dec 28. Erratum in: Ann Surg Oncol. 2012 Jul;19(7):2420. link to original article link to PMC article PubMed
Adjuvant therapy
Imatinib monotherapy
Regimen variant #1, 12 months of treatment
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Dematteo et al. 2009 (ACOSOG Z9001) | 2002-2007 | Phase 3 (E-RT-esc) | Placebo | Superior RFS (primary endpoint) RFS12: 98% vs 83% (HR 0.35, 95% CI 0.22-0.53) |
Joensuu et al. 2012 (SSG XVIII/AIO) | 2004-2008 | Phase 3 (C) | Imatinib x 36 mos | Inferior OS1 |
1Reported efficacy for SSG XVIII/AIO is based on the 2020 update.
Treatment is started within 12 weeks after surgery. While this is the FDA-recommended dose, it is noted that the optimal treatment duration is unknown.
Biomarker eligibility criteria
- Kit (CD117) positive
Preceding treatment
Regimen variant #2, 2 years of treatment
Study | Dates of enrollment | Evidence |
---|---|---|
Eisenberg et al. 2009 (RTOG 0132) | 2002-2006 | Phase 2 |
Biomarker eligibility criteria
- Kit (CD117) positive
Regimen variant #3, 3 years of treatment
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Joensuu et al. 2012 (SSG XVIII/AIO) | 2004-2008 | Phase 3 (E-RT-esc) | Imatinib x 12 mos | Superior OS1 (secondary endpoint) OS120: 79% vs 65.3% (HR 0.55, 95% CI 0.37-0.83) Superior RFS (primary endpoint) RFS60: 65.6% vs 47.9% (HR 0.46, 95% CI 0.32-0.65) |
1Reported efficacy is based on the 2020 update.
Treatment is to be started within 12 weeks after surgery. While this is the FDA-recommended dose, it is noted that the optimal treatment duration is unknown.
Biomarker eligibility criteria
- Kit (CD117) positive
Preceding treatment
References
- RTOG 0132: Eisenberg BL, Harris J, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M. Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol. 2009 Jan 1;99(1):42-7. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- Update: Wang D, Zhang Q, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M, Eisenberg BL. Phase II trial of neoadjuvant/adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors: long-term follow-up results of Radiation Therapy Oncology Group 0132. Ann Surg Oncol. 2012 Apr;19(4):1074-80. Epub 2011 Dec 28. Erratum in: Ann Surg Oncol. 2012 Jul;19(7):2420. link to original article link to PMC article PubMed
- ACOSOG Z9001: Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K; American College of Surgeons Oncology Group. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Mar 28;373(9669):1097-104. Epub 2009 Mar 18. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00041197
- SSG XVIII/AIO: Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schütte J, Ramadori G, Hohenberger P, Duyster J, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Sarlomo-Rikala M, Nilsson B, Sihto H, Monge OR, Bono P, Kallio R, Vehtari A, Leinonen M, Alvegård T, Reichardt P. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA. 2012 Mar 28;307(12):1265-72. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00116935
- Update: Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hartmann JT, Pink D, Ramadori G, Hohenberger P, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Nilsson B, Sihto H, Bono P, Kallio R, Junnila J, Alvegård T, Reichardt P. Adjuvant imatinib for high-risk GI stromal tumor: analysis of a randomized trial. J Clin Oncol. 2016 Jan 20;34(3):244-50. Epub 2015 Nov 2. link to original article PubMed
- Update: Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hermes B, Schütte J, Cameron S, Hohenberger P, Jost PJ, Al-Batran SE, Lindner LH, Bauer S, Wardelmann E, Nilsson B, Kallio R, Jaakkola P, Junnila J, Alvegård T, Reichardt P. Survival Outcomes Associated With 3 Years vs 1 Year of Adjuvant Imatinib for Patients With High-Risk Gastrointestinal Stromal Tumors: An Analysis of a Randomized Clinical Trial After 10-Year Follow-up. JAMA Oncol. 2020 Aug 1;6(8):1241-1246. link to original article link to PMC article PubMed
- IMADGIST: NCT02260505
Metastatic or unresectable disease, all lines of therapy
Imatinib monotherapy
Regimen variant #1, standard-dose (400 mg/day)
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Demetri et al. 2002 | 2000-07 to 2001-04 | Phase 3 (C) | Imatinib; higher-dose (600 mg/day) | Did not meet primary endpoint of ORR |
Blanke et al. 2008 (SWOG S0033) | 2000-12-15 to 2001-09-01 | Phase 3 (C) | Imatinib; high-dose (800 mg/day) | Did not meet co-primary endpoints of PFS/OS |
Verweij et al. 2004 (EORTC 62005) | 2001-02 to 2002-02 | Phase 3 (C) | Imatinib; high-dose | Did not meet primary endpoint of PFS1 |
Blay et al. 2007 (BFR14) | 2002-2004 | Phase 3 (C) | 1. Imatinib x 1 y 2. Imatinib x 3 y |
Superior PFS |
Blanke et al. 2015 (SWOG S0502) | 2008-04-15 to 2009-10-01 | Phase 3 (C) | Imatinib & Bevacizumab | Not reported |
Blay et al. 2015 (ENESTg1) | 2009-2011 | Phase 3 (C) | Nilotinib | Superior PFS |
Kang et al. 2013 (RIGHT) | 2010-2013 | Phase 3 (E-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 1.8 vs 0.9 mo (HR 0.46, 95% CI 0.27-0.76) |
1Reported efficacy for EORTC 62005 is based on the 2017 update.
Note: This arm of SWOG S0033 had pre-planned dose escalation to 800 mg/day at the time of progression. BFR14 had two separate comparisons, to one year and to three years of imatinib versus continuous (this arm); the efficacy outcome was the same in both reports.
Prior treatment criteria
- Demetri et al. 2002 & SWOG S0033: Any number of prior chemotherapy regimens
- BFR14: None specified
- SWOG S0502 & ENESTg1: None allowed (untreated)
- RIGHT: Failure of imatinib & sunitinib
Regimen variant #2, higher-dose (600 mg/day)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Demetri et al. 2002 | 2000-07 to 2001-04 | Phase 3 (E-esc) | Imatinib; standard-dose (400 mg/day) | Did not meet primary endpoint of ORR |
Prior treatment criteria
- Demetri et al. 2002: Any number of prior chemotherapy regimens
Regimen variant #3, high-dose (800 mg/day)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Van Oosterom et al. 2001 | 2000 | Phase 1, fewer than 20 pts in this cohort | ||
Verweij et al. 2003 | Not reported | Phase 2 | ||
Blanke et al. 2008 (SWOG S0033) | 2000-12-15 to 2001-09-01 | Phase 3 (E-RT-esc) | Imatinib; standard-dose with pre-planned dose-escalation at progression | Did not meet co-primary endpoints of PFS/OS |
Verweij et al. 2004 (EORTC 62005) | 2001-02 to 2002-02 | Phase 3 (E-RT-esc) | Imatinib; standard-dose | Did not meet primary endpoint of PFS1 |
Blanke et al. 2015 (SWOG S0502) | 2008-04-15 to 2009-10-01 | Phase 3 (C) | Imatinib & Bevacizumab | Not reported |
Blay et al. 2015 (ENESTg1) | 2009-2011 | Phase 3 (C) | Nilotinib | Superior PFS |
1Reported efficacy for EORTC 62005 is based on the 2017 update.
Note: this was the MTD in Van Oosterom et al. 2001. In some studies, high-dose imatinib was offered to patients with KIT exon 9 mutations in ENESTg1 and SWOG S0502; all other patients received standard-dose imatinib.
Prior treatment criteria
- SWOG S0033: Any number of prior chemotherapy regimens
- SWOG S0502 & ENESTg1: None allowed (untreated)
References
- Phase 1: van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, Martens M, Webb A, Sciot R, Van Glabbeke M, Silberman S, Nielsen OS; EORTC Soft Tissue and Bone Sarcoma Group. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet. 2001 Oct 27;358(9291):1421-3. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002 Aug 15;347(7):472-80. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Verweij J, van Oosterom A, Blay JY, Judson I, Rodenhuis S, van der Graaf W, Radford J, Le Cesne A, Hogendoorn PC, di Paola ED, Brown M, Nielsen OS; EORTC Soft Tissue and Bone Sarcoma Group. Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target: results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study. Eur J Cancer. 2003 Sep;39(14):2006-11. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- EORTC 62005: Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, Issels R, van Oosterom A, Hogendoorn PC, Van Glabbeke M, Bertulli R, Judson I. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004 Sep 25-Oct 1;364(9440):1127-34. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00685828
- Update: Zalcberg JR, Verweij J, Casali PG, Le Cesne A, Reichardt P, Blay JY, Schlemmer M, Van Glabbeke M, Brown M, Judson IR; EORTC Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian Gastrointestinal Trials Group. Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg. Eur J Cancer. 2005 Aug;41(12):1751-7. link to original article PubMed
- Update: Casali PG, Zalcberg J, Le Cesne A, Reichardt P, Blay JY, Lindner LH, Judson IR, Schöffski P, Leyvraz S, Italiano A, Grünwald V, Pousa AL, Kotasek D, Sleijfer S, Kerst JM, Rutkowski P, Fumagalli E, Hogendoorn P, Litière S, Marreaud S, van der Graaf W, Gronchi A, Verweij J; EORTC Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian Gastrointestinal Trials Group. Ten-year progression-free and overall survival in patients with unresectable or metastatic GI stromal tumors: long-term analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group intergroup phase III randomized trial on imatinib at two dose levels. J Clin Oncol. 2017 May 20;35(15):1713-1720. Epub 2017 Mar 31. link to original article PubMed
- BFR14: Blay JY, Le Cesne A, Ray-Coquard I, Bui B, Duffaud F, Delbaldo C, Adenis A, Viens P, Rios M, Bompas E, Cupissol D, Guillemet C, Kerbrat P, Fayette J, Chabaud S, Berthaud P, Perol D; French Sarcoma Group. Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol. 2007 Mar 20;25(9):1107-13. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00367861
- Update: Le Cesne A, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Cioffi A, Emile JF, Chabaud S, Pérol D, Blay JY; French Sarcoma Group. Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol. 2010 Oct;11(10):942-9. Epub 2010 Sep 21. link to original article dosing details in abstract have been reviewed by our editors PubMed
- SWOG S0033: Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, Raymond AK, Bramwell VH, Baker LH, Maki RG, Tanaka M, Hecht JR, Heinrich MC, Fletcher CD, Crowley JJ, Borden EC. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008 Feb 1;26(4):626-32. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00009906
- Update: Heinrich MC, Rankin C, Blanke CD, Demetri GD, Borden EC, Ryan CW, von Mehren M, Blackstein ME, Priebat DA, Tap WD, Maki RG, Corless CL, Fletcher JA, Owzar K, Crowley JJ, Benjamin RS, Baker LH. Correlation of Long-term Results of Imatinib in Advanced Gastrointestinal Stromal Tumors With Next-Generation Sequencing Results: Analysis of Phase 3 SWOG Intergroup Trial S0033. JAMA Oncol. 2017 Jul 1;3(7):944-952. Erratum in: JAMA Oncol. 2017 Jul 1;3(7):1002. link to original article link to PMC article PubMed
- Meta-analysis: Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST). Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. J Clin Oncol. 2010 Mar 1;28(7):1247-53. Epub 2010 Feb 1. link to original article link to PMC article PubMed
- RIGHT: Kang YK, Ryu MH, Yoo C, Ryoo BY, Kim HJ, Lee JJ, Nam BH, Ramaiya N, Jagannathan J, Demetri GD. Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1175-82. Epub 2013 Oct 18. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01151852
- ENESTg1: Blay JY, Shen L, Kang YK, Rutkowski P, Qin S, Nosov D, Wan D, Trent J, Srimuninnimit V, Pápai Z, Le Cesne A, Novick S, Taningco L, Mo S, Green S, Reichardt P, Demetri GD. Nilotinib versus imatinib as first-line therapy for patients with unresectable or metastatic gastrointestinal stromal tumours (ENESTg1): a randomised phase 3 trial. Lancet Oncol. 2015 May;16(5):550-60. Epub 2015 Apr 14. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00785785
- SWOG S0502: Blanke CD, Rankin C, Corless C, Eary JF, Mulder K, Okuno SH, George S, Heinrich M. S0502: A SWOG phase III randomized study of imatinib, with or without bevacizumab, in patients with untreated metastatic or unresectable gastrointestinal stromal tumors. Oncologist. 2015 Dec;20(12):1353-4. Epub 2015 Nov 17. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00324987
Metastatic or unresectable disease, second-line
Most trials define this context as imatinib-resistant.
Linsitinib monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Von Mehren et al. 2019 (SARC 022) | 2012-2013 | Phase 2 |
Patients in this study had wild-type GIST and had previously failed treatment with at least one prior TKI
References
- SARC 022: Von Mehren M, George S, Heinrich M, Schuetze S, Yap J, Yu J, Abbott A, Litwin S, Crowley J, Belinsky M, Janeway K, Hornick J, Flieder D, Chugh R, Rink L, Van den Abbeele A. Linsitinib (OSI-906) for the Treatment of Adult and Pediatric Wild-Type Gastrointestinal Stromal Tumors: a SARC Phase II Study. Clin Cancer Res. 2020 April; 15;26(8):1837-1845. Epub 2019 Dec 2. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01560260
Sunitinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Demetri et al. 2006 (A6181004) | 2003-2005 | Phase 3 (E-RT-esc) | Placebo | Superior TTP (primary endpoint) Median TTP: 27.3 vs 6.4 weeks (HR 0.33) |
Adenis et al. 2014 (AB07001) | 2009-2011 | Randomized Phase 2 (C) | Masitinib | Seems to have inferior OS |
Bauer et al. 2022 (INTRIGUE) | 2019 to not reported | Phase 3 (C) | Ripretinib | Did not meet primary endpoint of PFS Median PFS: 8.3 vs 8 mo (HR 0.95, 95% CI 0.75-1.22) |
Prior treatment criteria
- A6181004, AB07001, INTRIGUE: Failure of imatinib
Dose and schedule modifications
- Sunitinib (Sutent) dose may be decreased to 37.5 mg once per day or 25 mg once per day depending on tolerability
References
- A6181004: Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00075218
- Update: Demetri GD, Garrett CR, Schöffski P, Shah MH, Verweij J, Leyvraz S, Hurwitz HI, Pousa AL, Le Cesne A, Goldstein D, Paz-Ares L, Blay JY, McArthur GA, Xu QC, Huang X, Harmon CS, Tassell V, Cohen DP, Casali PG. Complete longitudinal analyses of the randomized, placebo-controlled, phase III trial of sunitinib in patients with gastrointestinal stromal tumor following imatinib failure. Clin Cancer Res. 2012 Jun 1;18(11):3170-9. link to original article link to PMC article PubMed
- AB07001: Adenis A, Blay JY, Bui-Nguyen B, Bouché O, Bertucci F, Isambert N, Bompas E, Chaigneau L, Domont J, Ray-Coquard I, Blésius A, Van Tine BA, Bulusu VR, Dubreuil P, Mansfield CD, Acin Y, Moussy A, Hermine O, Le Cesne A. Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial. Ann Oncol. 2014 Sep;25(9):1762-9. Epub 2014 Jul 25. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01506336
- INTRIGUE: Bauer S, Jones RL, Blay JY, Gelderblom H, George S, Schöffski P, von Mehren M, Zalcberg JR, Kang YK, Razak AA, Trent J, Attia S, Le Cesne A, Su Y, Meade J, Wang T, Sherman ML, Ruiz-Soto R, Heinrich MC. Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Dec 1;40(34):3918-3928. Epub 2022 Aug 10. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT03673501
- AB11002: NCT01694277
Metastatic or unresectable disease, third-line
Cabozantinib monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Schöffski et al. 2020 (CaboGIST) | 2017-2018 | Phase 2 |
Prior treatment criteria
- CaboGIST: Failure of imatinib and sunitinib
References
- CaboGIST: Schöffski P, Mir O, Kasper B, Papai Z, Blay JY, Italiano A, Benson C, Kopeckova K, Ali N, Dileo P, LeCesne A, Menge F, Cousin S, Wardelmann E, Wozniak A, Marreaud S, Litiere S, Zaffaroni F, Nzokirantevye A, Vanden Bempt I, Gelderblom H. Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 'CaboGIST'. Eur J Cancer. 2020 Jul;134:62-74. Epub 2020 May 26. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02216578
Pazopanib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mir et al. 2016 (PAZOGIST) | 2011-2013 | Randomized Phase 2 (E-esc) | Best supportive care | Seems to have superior PFS (primary endpoint) Median PFS: 3.4 vs 2.3 mo (HR 0.59, 95% CI 0.37-0.96) |
Prior treatment criteria
- PAZOGIST: Failure of imatinib and sunitinib
References
- PAZOGIST: Mir O, Cropet C, Toulmonde M, Cesne AL, Molimard M, Bompas E, Cassier P, Ray-Coquard I, Rios M, Adenis A, Italiano A, Bouché O, Chauzit E, Duffaud F, Bertucci F, Isambert N, Gautier J, Blay JY, Pérol D; PAZOGIST study group of the French Sarcoma Groupe-Groupe d'Etude des Tumeurs Osseuses (GSF-GETO). Pazopanib plus best supportive care versus best supportive care alone in advanced gastrointestinal stromal tumours resistant to imatinib and sunitinib (PAZOGIST): a randomised, multicentre, open-label phase 2 trial. Lancet Oncol. 2016 May;17(5):632-41. Epub 2016 Apr 5. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01323400
Regorafenib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Demetri et al. 2012 (GRID) | 2011-01 to 2011-08 | Phase 3 (E-RT-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 4.8 vs 0.9 mo (HR 0.27, 95% CI 0.19-0.39) |
Kang et al. 2021 (VOYAGER) | 2018-03-26 to 2019-11-15 | Phase 3 (C) | Avapritinib | Might have superior PFS Median PFS: 5.6 vs 4.2 mo (HR 0.80, 95% CI 0.64-1.01) |
Prior treatment criteria
- GRID: Failure of imatinib & sunitinib
- VOYAGER: Failure of imatinib and one or two additional TKIs
References
- GRID: Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Schöffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG; GRID study investigators. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):295-302. Epub 2012 Nov 22. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01271712
- VOYAGER: Kang YK, George S, Jones RL, Rutkowski P, Shen L, Mir O, Patel S, Zhou Y, von Mehren M, Hohenberger P, Villalobos V, Brahmi M, Tap WD, Trent J, Pantaleo MA, Schöffski P, He K, Hew P, Newberry K, Roche M, Heinrich MC, Bauer S. Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study. J Clin Oncol. 2021 Oct 1;39(28):3128-3139. Epub 2021 Aug 3. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT03465722
Sorafenib monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Park et al. 2012 (SMC 2009-08-102) | 2009-2010 | Phase 2 |
Prior treatment criteria
- SMC 2009-08-102: Failure of 2 or more TKIs
References
- Abstract: Kindler HL, Campbell NP, Wroblewski K, Maki RG, D’Adamo DR, Chow WA, Gandara DR, Antonescu C, Stadler WM, Vokes EE. Sorafenib (SOR) in patients (pts) with imatinib (IM) and sunitinib (SU)-resistant (RES) gastrointestinal stromal tumors (GIST): Final results of a University of Chicago Phase II Consortium trial. 2011. 29 (15_suppl) 10009-10009. link to original article (abstract only)
- SMC 2009-08-102: Park SH, Ryu MH, Ryoo BY, Im SA, Kwon HC, Lee SS, Park SR, Kang BY, Kang YK; Korean gastrointestinal stromal tumors study group. Sorafenib in patients with metastatic gastrointestinal stromal tumors who failed two or more prior tyrosine kinase inhibitors: a phase II study of Korean gastrointestinal stromal tumors study group. Invest New Drugs. 2012 Dec; 30(6) 2377-83. Epub 2012 Jan 25. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01091207
Metastatic or unresectable disease, fourth-line
Many trials define this context as imatinib-, sunitinib-, and regorafenib-resistant.
Avapritinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence |
---|---|---|
Heinrich et al. 2020 (NAVIGATOR) | 2015-10-26 to 2018-11-16 | Phase 1 (RT) |
Note: Patients enrolled in this study met either the biomarker eligibility OR the prior treatment criteria. This is the recommended phase 2 dose.
Prior treatment criteria
- Treatment failure with imatinib and at least 1 additional tyrosine kinase inhibitor
Biomarker eligibility criteria
- Gene: PDGFRA
- Alteration: D842V
Targeted therapy
- Avapritinib (Ayvakit) 300 mg PO once per day, taken on an empty stomach (at least 1 hour before and 2 hours after a meal)
Continued indefinitely
References
- NAVIGATOR: Heinrich MC, Jones RL, von Mehren M, Schöffski P, Serrano C, Kang YK, Cassier PA, Mir O, Eskens F, Tap WD, Rutkowski P, Chawla SP, Trent J, Tugnait M, Evans EK, Lauz T, Zhou T, Roche M, Wolf BB, Bauer S, George S. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020 Jul;21(7):935-946. Erratum in: Lancet Oncol. 2020 Sep;21(9):e418. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02508532
- Update: Jones RL, Serrano C, von Mehren M, George S, Heinrich MC, Kang YK, Schöffski P, Cassier PA, Mir O, Chawla SP, Eskens FALM, Rutkowski P, Tap WD, Zhou T, Roche M, Bauer S. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. Eur J Cancer. 2021 Mar;145:132-142. Epub 2021 Jan 16. link to original article link to PMC article PubMed
Pimitespib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kurokawa et al. 2022 (CHAPTER-GIST-301) | 2018-2020 | Phase 3 (E-esc) | Placebo | Superior OS (secondary endpoint) Median OS: 13.8 vs 7.6 mo (HR 0.42, 95% CI 0.21-0.85) |
Prior treatment criteria
- CHAPTER-GIST-301: Failure of imatinib, sunitinib, and regorafenib
Targeted therapy
- Pimitespib (Jeselhy) 160 mg PO once per day on days 1 to 5, 8 to 12, 15 to 19
21-day cycles
References
- CHAPTER-GIST-301: Kurokawa Y, Honma Y, Sawaki A, Naito Y, Iwagami S, Komatsu Y, Takahashi T, Nishida T, Doi T. Pimitespib in patients with advanced gastrointestinal stromal tumor (CHAPTER-GIST-301): a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol. 2022 Sep;33(9):959-967. Epub 2022 Jun 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed JapicCTI-184094
Ripretinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Blay et al. 2020 (INVICTUS) | 2018-02-27 to 2018-11-16 | Phase 3 (E-RT-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 6.3 vs 1 mo (HR 0.15, 95% CI 0.09-0.25) |
Prior treatment criteria
- Failure of imatinib, sunitinib, and regorafenib
References
- INVICTUS: Blay JY, Serrano C, Heinrich MC, Zalcberg J, Bauer S, Gelderblom H, Schöffski P, Jones RL, Attia S, D'Amato G, Chi P, Reichardt P, Meade J, Shi K, Ruiz-Soto R, George S, von Mehren M. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jul;21(7):923-934. Epub 2020 Jun 5. Erratum in: Lancet Oncol. 2020 Jul;21(7):e341. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT03353753