Difference between revisions of "Gastrointestinal stromal tumor"
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{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
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=Guidelines= | =Guidelines= | ||
==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] | ||
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===Older=== | ===Older=== | ||
*'''2018:''' Casali et al. [https://www.esmo.org/Guidelines/Sarcoma-and-GIST/Gastrointestinal-Stromal-Tumours Gastrointestinal stromal tumours: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up] | *'''2018:''' Casali et al. [https://www.esmo.org/Guidelines/Sarcoma-and-GIST/Gastrointestinal-Stromal-Tumours Gastrointestinal stromal tumours: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up] | ||
*'''2014:''' [http://annonc.oxfordjournals.org/content/25/suppl_3/iii21.full.pdf+html Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/25210085 PubMed] | *'''2014:''' [http://annonc.oxfordjournals.org/content/25/suppl_3/iii21.full.pdf+html Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/25210085 PubMed] | ||
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==[https://www.nccn.org/ NCCN]== | ==[https://www.nccn.org/ NCCN]== | ||
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*[https://www.nccn.org/professionals/physician_gls/pdf/gist.pdf NCCN Guidelines - GIST] | *[https://www.nccn.org/professionals/physician_gls/pdf/gist.pdf NCCN Guidelines - GIST] | ||
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=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;" | ||
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|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
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*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==== | ||
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*[[Surgery#Surgical_resection|Surgery]], then adjuvant [[#Imatinib_monotherapy_2|imatinib]] x 2 y, resumed as soon as possible postoperatively | *[[Surgery#Surgical_resection|Surgery]], then adjuvant [[#Imatinib_monotherapy_2|imatinib]] x 2 y, resumed as soon as possible postoperatively | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
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#'''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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606912/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18942073 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] | ##'''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] | ||
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=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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''<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;" | ||
Line 121: | Line 113: | ||
|- | |- | ||
|} | |} | ||
+ | <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==== | ||
− | |||
*[[#Imatinib_monotherapy|Neoadjuvant imatinib]], then [[Surgery#Surgical_resection|Surgery]] | *[[#Imatinib_monotherapy|Neoadjuvant imatinib]], then [[Surgery#Surgical_resection|Surgery]] | ||
− | + | </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" | ||
Line 156: | Line 148: | ||
''<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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606912/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18942073 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] | ##'''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] | ||
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=Metastatic or unresectable disease, all lines of therapy= | =Metastatic or unresectable disease, all lines of therapy= | ||
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==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 234: | Line 223: | ||
''<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.'' | ''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==== | ====Prior treatment criteria==== | ||
*Demetri et al. 2002: Any number of prior chemotherapy regimens | *Demetri et al. 2002: Any number of prior chemotherapy regimens | ||
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*SWOG S0502 & ENESTg1: None allowed (untreated) | *SWOG S0502 & ENESTg1: None allowed (untreated) | ||
*RIGHT: Failure of imatinib & sunitinib | *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''' | '''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;" | ||
Line 260: | Line 251: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Prior treatment criteria==== | ====Prior treatment criteria==== | ||
*Demetri et al. 2002: Any number of prior chemotherapy regimens | *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;" | ||
Line 315: | Line 308: | ||
''<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==== | ====Prior treatment criteria==== | ||
*SWOG S0033: Any number of prior chemotherapy regimens | *SWOG S0033: Any number of prior chemotherapy regimens | ||
*SWOG S0502 & ENESTg1: None allowed (untreated) | *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><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Protocol variant #4, standard-dose with pre-planned dose-escalation at progression {{#subobject:854522|Variant=1}}=== | ===Protocol variant #4, standard-dose with pre-planned dose-escalation at progression {{#subobject:854522|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 339: | Line 334: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Prior treatment criteria==== | ====Prior treatment criteria==== | ||
*SWOG S0033: Any number of prior chemotherapy regimens | *SWOG S0033: Any number of prior chemotherapy regimens | ||
+ | </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''' | '''Continued indefinitely''' | ||
− | |||
''Patients who progressed could receive high-dose therapy, as follows:'' | ''Patients who progressed could receive high-dose therapy, as follows:'' | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Imatinib (Gleevec)]] 400 mg PO twice per day | *[[Imatinib (Gleevec)]] 400 mg PO twice per 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] '''contains dosing details in abstract''' [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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11705489 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://doi.org/10.1056/nejmoa020461 link to original article] '''contains dosing details in manuscript''' [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://doi.org/10.1056/nejmoa020461 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12181401 PubMed] | ||
Line 371: | Line 362: | ||
#'''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25882987 PubMed] NCT00785785 | #'''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25882987 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. [https://doi.org/10.1634/theoncologist.2015-0295 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679092/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26576593 PubMed] NCT00324987 | #'''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] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679092/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26576593 PubMed] 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;" | ||
Line 387: | Line 376: | ||
| 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 | *[[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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31792037/ PubMed] 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31792037/ PubMed] NCT01560260 | ||
==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;" | ||
Line 423: | Line 408: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Prior treatment criteria==== | ====Prior treatment criteria==== | ||
*A6181004 & AB07001: Failure of imatinib | *A6181004 & AB07001: 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''' | ||
− | |||
====Dose modifications==== | ====Dose modifications==== | ||
*[[Sunitinib (Sutent)]] dose may be decreased to 37.5 mg once per day or 25 mg once per day depending on tolerability | *[[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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17046465 PubMed] 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://doi.org/10.1016/S0140-6736(06)69446-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17046465 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. [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] [https://pubmed.ncbi.nlm.nih.gov/25122671 PubMed] 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 | ||
#'''AB11002:''' NCT01694277 | #'''AB11002:''' 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;" | ||
Line 454: | Line 438: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Prior treatment criteria==== | ====Prior treatment criteria==== | ||
*CaboGIST: Failure of imatinib and sunitinib | *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 | ||
− | |||
'''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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32470848/ PubMed] NCT02216578 | #'''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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32470848/ PubMed] 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;" | ||
Line 482: | Line 466: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Prior treatment criteria==== | ====Prior treatment criteria==== | ||
*PAZOGIST: Failure of imatinib and sunitinib | *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 | *[[Pazopanib (Votrient)]] 800 mg PO once per day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27068858 PubMed] 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://doi.org/10.1016/S1470-2045(16)00075-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27068858 PubMed] NCT01323400 | ||
− | |||
==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;" | ||
Line 518: | Line 500: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Prior treatment criteria==== | ====Prior treatment criteria==== | ||
*GRID: Failure of imatinib & sunitinib | *GRID: Failure of imatinib & sunitinib | ||
*VOYAGER: Failure of imatinib and one or two additional TKIs | *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] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819942/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23177515 PubMed] 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] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819942/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23177515 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. [https://doi.org/10.1200/jco.21.00217 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478403/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34343033/ PubMed] 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] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478403/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34343033/ PubMed] NCT03465722 | ||
− | |||
==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;" | ||
Line 550: | Line 530: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Prior treatment criteria==== | ====Prior treatment criteria==== | ||
*SMC 2009-08-102: Failure of 2 or more TKIs | *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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22270258 PubMed] NCT01091207 | #'''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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22270258 PubMed] 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" | ||
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''Note: Patients in this study either had the PDGFRA D842V mutation or already had treatment failure with imatinib and ≥1 additional tyrosine kinase inhibitor. This is the recommended phase II dose.'' | ''Note: Patients in this study either had the PDGFRA D842V mutation or already had treatment failure with imatinib and ≥1 additional tyrosine kinase inhibitor. This is the recommended phase II dose.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
− | |||
*Gene: PDGFRA | *Gene: PDGFRA | ||
*Alteration: D842V | *Alteration: D842V | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
[[Avapritinib (Ayvakit)]] 300 mg PO once per day on an empty stomach (at least 1 hour before and 2 hours after a meal) | [[Avapritinib (Ayvakit)]] 300 mg PO once per day 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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32615108/ PubMed] NCT02508532 | #'''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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32615108/ 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. [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://pubmed.ncbi.nlm.nih.gov/33465704/ PubMed] | ||
− | |||
==Pimitespib monotherapy {{#subobject:bhg1ve|Regimen=1}}== | ==Pimitespib monotherapy {{#subobject:bhg1ve|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:6huqrc|Variant=1}}=== | ===Regimen {{#subobject:6huqrc|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Prior treatment criteria==== | ====Prior treatment criteria==== | ||
*CHAPTER-GIST-301: Failure of imatinib, sunitinib, and regorafenib | *CHAPTER-GIST-301: Failure of imatinib, sunitinib, and regorafenib | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Pimitespib (Jeselhy)]] 160 mg PO once per day on days 1 to 5, 8 to 12, 15 to 19 | *[[Pimitespib (Jeselhy)]] 160 mg PO once per day on days 1 to 5, 8 to 12, 15 to 19 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===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 Jun 8:S0923-7534(22)01718-5. Epub ahead of print. [https://doi.org/10.1016/j.annonc.2022.05.518 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35688358/ PubMed] JapicCTI-184094 | #'''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 Jun 8:S0923-7534(22)01718-5. Epub ahead of print. [https://doi.org/10.1016/j.annonc.2022.05.518 link to original article] '''contains dosing details in manuscript''' [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" | ||
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|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Prior treatment criteria==== | ====Prior treatment criteria==== | ||
*Failure of imatinib, sunitinib, and regorafenib | *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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32511981 PubMed] 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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32511981 PubMed] NCT03353753 | ||
− | |||
[[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]] |
Revision as of 21:08, 11 October 2022
Page editor | Section editor | ||
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Eric Marks, MD Boston University Boston, MA |
Elizabeth J. Davis, MD Vanderbilt University Nashville, TN ejdavis25 |
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
ESMO/EURACAN/GENTURIS
- 2021: Casali et al. Gastrointestinal stromal tumours: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up
Older
- 2018: Casali et al. Gastrointestinal stromal tumours: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up
- 2014: Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
NCCN
Neoadjuvant therapy
Imatinib monotherapy
Regimen
Study | Years 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 contains dosing details in manuscript 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Dematteo et al. 2009 (ACOSOG Z9001) | 2002-2007 | Phase 3 (E-RT-esc) | Placebo | Superior RFS 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 | Years of enrollment | Evidence |
---|---|---|
Eisenberg et al. 2009 (RTOG 0132) | 2002-2006 | Phase 2 |
Biomarker eligibility criteria
- Kit (CD117) positive
Preceding treatment
- Neoadjuvant imatinib, then Surgery
Regimen variant #3, 3 years of treatment
FDA-recommended dose |
Study | Years 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 (HR 0.55, 95% CI 0.37-0.83) |
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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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
Metastatic or unresectable disease, all lines of therapy
Imatinib monotherapy
Regimen variant #1, standard-dose (400 mg/day)
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Demetri et al. 2002 | 2000-2001 | Phase 3 (C) | Imatinib; higher-dose (600 mg/day) | Did not meet primary endpoint of ORR |
Verweij et al. 2004 (EORTC 62005) | 2001-2002 | 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) | 2008-2009 | 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 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.
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: 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Demetri et al. 2002 | 2000-2001 | 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Van Oosterom et al. 2001 | 2000 | Phase 1, <20 pts in this cohort | ||
Verweij et al. 2003 | NR | Phase 2 | ||
Verweij et al. 2004 (EORTC 62005) | 2001-2002 | Phase 3 (E-RT-esc) | Imatinib; standard-dose | Did not meet primary endpoint of PFS1 |
Blanke et al. 2008 (SWOG S0033) | 2001-2002 | Phase 3 (E-RT-esc) | Imatinib; standard-dose with pre-planned dose-escalation at progression | Did not meet primary endpoints of PFS/OS |
Blanke et al. 2015 (SWOG S0502) | 2008-2009 | 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)
Protocol variant #4, standard-dose with pre-planned dose-escalation at progression
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Blanke et al. 2008 (SWOG S0033) | 2001-2002 | Phase 3 (C) | Imatinib; high-dose (800 mg/day) | Did not meet primary endpoints of PFS/OS |
Prior treatment criteria
- SWOG S0033: Any number of prior chemotherapy regimens
Targeted therapy
- Imatinib (Gleevec) 400 mg PO once per day
Continued indefinitely Patients who progressed could receive high-dose therapy, as follows:
Targeted therapy
- Imatinib (Gleevec) 400 mg PO twice per day
Continued indefinitely
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 contains dosing details in abstract 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in abstract 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 contains dosing details in abstract 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 contains dosing details in abstract 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript link to PMC article PubMed NCT00324987
Metastatic or unresectable disease, second-line
Most trials define this context as imatinib-resistant.
Linsitinib monotherapy
Regimen
Study | Years 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 contains dosing details in manuscript PubMed NCT01560260
Sunitinib monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Demetri et al. 2006 (A6181004) | 2003-2005 | Phase 3 (E-RT-esc) | Placebo | Superior TTP 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 |
Prior treatment criteria
- A6181004 & AB07001: Failure of imatinib
Targeted therapy
- Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28
42-day cycles
Dose 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 contains dosing details in manuscript 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 PubMed NCT01506336
- AB11002: NCT01694277
Metastatic or unresectable disease, third-line
Cabozantinib monotherapy
Regimen
Study | Years 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 contains dosing details in abstract PubMed NCT02216578
Pazopanib monotherapy
Regimen
Study | Years 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 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 contains dosing details in abstract PubMed NCT01323400
Regorafenib monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Demetri et al. 2012 (GRID) | 2011 | Phase 3 (E-RT-esc) | Placebo | Superior PFS Median PFS: 4.8 vs 0.9 mo (HR 0.27, 95% CI 0.19-0.39) |
Kang et al. 2021 (VOYAGER) | 2018-2019 | 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 contains dosing details in manuscript 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 contains dosing details in abstract link to PMC article PubMed NCT03465722
Sorafenib monotherapy
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Kindler et al. 2011 | NR | Phase 2 |
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 contains dosing details in abstract 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 | Years of enrollment | Evidence |
---|---|---|
Heinrich et al. 2020 (NAVIGATOR) | 2015-2018 | Phase 1 (RT) |
Note: Patients in this study either had the PDGFRA D842V mutation or already had treatment failure with imatinib and ≥1 additional tyrosine kinase inhibitor. This is the recommended phase II dose.
Biomarker eligibility criteria
- Gene: PDGFRA
- Alteration: D842V
Targeted therapy
Avapritinib (Ayvakit) 300 mg PO once per day 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 contains dosing details in abstract 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 PubMed
Pimitespib monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kurokawa et al. 2022 (CHAPTER-GIST-301) | 2018-2020 | Phase 3 (E-esc) | Placebo | Superior OS 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 Jun 8:S0923-7534(22)01718-5. Epub ahead of print. link to original article contains dosing details in manuscript PubMed JapicCTI-184094
Ripretinib monotherapy
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Blay et al. 2020 (INVICTUS) | 2018 | Phase 3 (E-RT-esc) | Placebo | Superior PFS 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 contains dosing details in abstract PubMed NCT03353753