Difference between revisions of "Gastrointestinal stromal tumor"
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m (Added sorafenib - trying to change color in table to light green to reflect phase II not III study) Tag: visualeditor |
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=Guidelines= | =Guidelines= | ||
==[http://www.esmo.org/ ESMO]== | ==[http://www.esmo.org/ ESMO]== | ||
| + | |||
*'''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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/25210085 PubMed] | ||
==ESMO/EURACAN== | ==ESMO/EURACAN== | ||
| + | |||
*'''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] | ||
==[https://www.nccn.org/ NCCN]== | ==[https://www.nccn.org/ NCCN]== | ||
| + | |||
*[https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf NCCN Guidelines - Soft Tissue Sarcoma] | *[https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf NCCN Guidelines - Soft Tissue Sarcoma] | ||
| Line 31: | Line 34: | ||
===Regimen {{#subobject:3b663c|Variant=1}}=== | ===Regimen {{#subobject:3b663c|Variant=1}}=== | ||
{| class="wikitable" style="width: 50%; text-align:center;" | {| class="wikitable" style="width: 50%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606912/ Eisenberg et al. 2009 (RTOG 0132)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606912/ Eisenberg et al. 2009 (RTOG 0132)] | ||
| − | |style="background-color:#91cf61"|Phase II | + | | style="background-color:#91cf61" |Phase II |
|- | |- | ||
|} | |} | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
| + | |||
*[[Imatinib (Gleevec)]] 600 mg PO once per day | *[[Imatinib (Gleevec)]] 600 mg PO once per day | ||
| Line 44: | Line 48: | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
| + | |||
*[[Surgery#Surgical_resection|Surgery]], then [[#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 | ||
===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. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606912/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800166/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22203182 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. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606912/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800166/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22203182 PubMed] | ||
=Adjuvant therapy= | =Adjuvant therapy= | ||
| Line 62: | Line 68: | ||
|} | |} | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
| − | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
| − | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
|[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)] | ||
| − | |style="background-color:#1a9851"|Phase III (E-RT) | + | | style="background-color:#1a9851" |Phase III (E-RT) |
|[[#Placebo|Placebo]] | |[[#Placebo|Placebo]] | ||
| − | |style="background-color:#1a9850"|Superior RFS | + | | style="background-color:#1a9850" |Superior RFS |
|- | |- | ||
|[http://jama.jamanetwork.com/article.aspx?articleid=1105116 Joensuu et al. 2012 (SSG XVIII/AIO)] | |[http://jama.jamanetwork.com/article.aspx?articleid=1105116 Joensuu et al. 2012 (SSG XVIII/AIO)] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|Imatinib x 36 mos | |Imatinib x 36 mos | ||
| − | |style="background-color:#fc8d59"|Seems to have inferior OS | + | | style="background-color:#fc8d59" |Seems to have inferior OS |
|- | |- | ||
|} | |} | ||
''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.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
| + | |||
*[[Surgery#Surgical_resection|Surgery]] | *[[Surgery#Surgical_resection|Surgery]] | ||
| + | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
| + | |||
*[[Imatinib (Gleevec)]] 400 mg PO once per day | *[[Imatinib (Gleevec)]] 400 mg PO once per day | ||
| Line 88: | Line 97: | ||
===Variant #2, 2 years of treatment {{#subobject:3c163c|Variant=1}}=== | ===Variant #2, 2 years of treatment {{#subobject:3c163c|Variant=1}}=== | ||
{| class="wikitable" style="width: 50%; text-align:center;" | {| class="wikitable" style="width: 50%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606912/ Eisenberg et al. 2009 (RTOG 0132)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606912/ Eisenberg et al. 2009 (RTOG 0132)] | ||
| − | |style="background-color:#91cf61"|Phase II | + | | style="background-color:#91cf61" |Phase II |
|- | |- | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
| + | |||
*[[#Imatinib_monotherapy|Neoadjuvant imatinib]], then [[Surgery#Surgical_resection|Surgery]] | *[[#Imatinib_monotherapy|Neoadjuvant imatinib]], then [[Surgery#Surgical_resection|Surgery]] | ||
| + | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
| + | |||
*[[Imatinib (Gleevec)]] 600 mg PO once per day | *[[Imatinib (Gleevec)]] 600 mg PO once per day | ||
| Line 108: | Line 120: | ||
|} | |} | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
| − | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
| − | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
|[http://jama.jamanetwork.com/article.aspx?articleid=1105116 Joensuu et al. 2012 (SSG XVIII/AIO)] | |[http://jama.jamanetwork.com/article.aspx?articleid=1105116 Joensuu et al. 2012 (SSG XVIII/AIO)] | ||
| − | |style="background-color:#1a9851"|Phase III (E) | + | | style="background-color:#1a9851" |Phase III (E) |
|Imatinib x 12 mos | |Imatinib x 12 mos | ||
| − | |style="background-color:#91cf60"|Seems to have superior OS | + | | style="background-color:#91cf60" |Seems to have superior OS |
|- | |- | ||
|} | |} | ||
''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.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
| + | |||
*[[Surgery#Surgical_resection|Surgery]] | *[[Surgery#Surgical_resection|Surgery]] | ||
| + | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
| + | |||
*[[Imatinib (Gleevec)]] 400 mg PO once per day | *[[Imatinib (Gleevec)]] 400 mg PO once per day | ||
| Line 128: | Line 143: | ||
===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. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606912/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800166/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22203182 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. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606912/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18942073 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 (ACOSOG) Intergroup Adjuvant GIST Study Team. 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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915459/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915459/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19303137 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800166/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22203182 PubMed] |
| − | # '''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. [http://jama.jamanetwork.com/article.aspx?articleid=1105116 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22453568 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 (ACOSOG) Intergroup Adjuvant GIST Study Team. 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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915459/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915459/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19303137 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://ascopubs.org/doi/full/10.1200/JCO.2015.62.9170 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26527782 PubMed] | + | #'''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. [http://jama.jamanetwork.com/article.aspx?articleid=1105116 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22453568 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://ascopubs.org/doi/full/10.1200/JCO.2015.62.9170 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26527782 PubMed] | ||
==Placebo== | ==Placebo== | ||
| Line 142: | Line 158: | ||
===Regimen=== | ===Regimen=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
| − | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
| − | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
|[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)] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|[[#Imatinib_monotherapy_2|Imatinib x 12 mos]] | |[[#Imatinib_monotherapy_2|Imatinib x 12 mos]] | ||
| − | |style="background-color:#d73027"|Inferior RFS | + | | style="background-color:#d73027" |Inferior RFS |
|- | |- | ||
|} | |} | ||
''No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.'' | ''No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
| + | |||
*[[Surgery#Surgical_resection|Surgery]] | *[[Surgery#Surgical_resection|Surgery]] | ||
===References=== | ===References=== | ||
| − | # '''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 (ACOSOG) Intergroup Adjuvant GIST Study Team. 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. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915459/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19303137 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 (ACOSOG) Intergroup Adjuvant GIST Study Team. 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. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915459/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19303137 PubMed] | ||
=Metastatic or unresectable disease= | =Metastatic or unresectable disease= | ||
| Line 169: | Line 187: | ||
===Regimen=== | ===Regimen=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
| − | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
| − | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
|[https://academic.oup.com/annonc/article/23/7/1680/202540 Reichardt et al. 2012 (ENEST g3)] | |[https://academic.oup.com/annonc/article/23/7/1680/202540 Reichardt et al. 2012 (ENEST g3)] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|Nilotinib | |Nilotinib | ||
| style="background-color:#ffffbf" |Seems not superior | | style="background-color:#ffffbf" |Seems not superior | ||
|- | |- | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00075-9/fulltext Mir et al. 2016 (PAZOGIST)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00075-9/fulltext Mir et al. 2016 (PAZOGIST)] | ||
| − | |style="background-color:#1a9851"|Randomized Phase II (C) | + | | style="background-color:#1a9851" |Randomized Phase II (C) |
|[[#Pazopanib_monotherapy|Pazopanib]] | |[[#Pazopanib_monotherapy|Pazopanib]] | ||
| − | |style="background-color:#fc8d59"|Seems to have inferior PFS | + | | style="background-color:#fc8d59" |Seems to have inferior PFS |
|- | |- | ||
|} | |} | ||
| Line 188: | Line 206: | ||
===References=== | ===References=== | ||
| − | # '''ENEST g3:''' Reichardt P, Blay JY, Gelderblom H, Schlemmer M, Demetri GD, Bui-Nguyen B, McArthur GA, Yazji S, Hsu Y, Galetic I, Rutkowski P. Phase III study of nilotinib versus best supportive care with or without a TKI in patients with gastrointestinal stromal tumors resistant to or intolerant of imatinib and sunitinib. Ann Oncol. 2012 Jul;23(7):1680-7. Epub 2012 Feb 21. [https://academic.oup.com/annonc/article/23/7/1680/202540 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22357255 PubMed] | + | |
| − | # '''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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00075-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27068858 PubMed] | + | #'''ENEST g3:''' Reichardt P, Blay JY, Gelderblom H, Schlemmer M, Demetri GD, Bui-Nguyen B, McArthur GA, Yazji S, Hsu Y, Galetic I, Rutkowski P. Phase III study of nilotinib versus best supportive care with or without a TKI in patients with gastrointestinal stromal tumors resistant to or intolerant of imatinib and sunitinib. Ann Oncol. 2012 Jul;23(7):1680-7. Epub 2012 Feb 21. [https://academic.oup.com/annonc/article/23/7/1680/202540 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22357255 PubMed] |
| + | #'''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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00075-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27068858 PubMed] | ||
==Imatinib monotherapy {{#subobject:16a4ba|Regimen=1}}== | ==Imatinib monotherapy {{#subobject:16a4ba|Regimen=1}}== | ||
| Line 202: | Line 221: | ||
|} | |} | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
| − | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
| − | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
|[https://www.nejm.org/doi/full/10.1056/NEJMoa020461 Demetri et al. 2002] | |[https://www.nejm.org/doi/full/10.1056/NEJMoa020461 Demetri et al. 2002] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|[[#Imatinib_monotherapy_3|Imatinib]]; higher-dose (600 mg/day) | |[[#Imatinib_monotherapy_3|Imatinib]]; higher-dose (600 mg/day) | ||
| − | |style="background-color:#ffffbf"|Seems not superior | + | | style="background-color:#ffffbf" |Seems not superior |
|- | |- | ||
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(04)17098-0/fulltext Verweij et al. 2004 (EORTC 62005)] | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(04)17098-0/fulltext Verweij et al. 2004 (EORTC 62005)] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|[[#Imatinib_monotherapy_3|Imatinib]]; high-dose | |[[#Imatinib_monotherapy_3|Imatinib]]; high-dose | ||
| − | |style="background-color:#ffffbf"|Seems not superior (*) | + | | style="background-color:#ffffbf" |Seems not superior (*) |
|- | |- | ||
|[https://ascopubs.org/doi/full/10.1200/JCO.2006.09.0183 Blay et al. 2007 (BFR14)] | |[https://ascopubs.org/doi/full/10.1200/JCO.2006.09.0183 Blay et al. 2007 (BFR14)] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|1. [[#Imatinib_monotherapy_3|Imatinib]]; 1 year<br> 2. [[#Imatinib_monotherapy_3|Imatinib]]; 3 years | |1. [[#Imatinib_monotherapy_3|Imatinib]]; 1 year<br> 2. [[#Imatinib_monotherapy_3|Imatinib]]; 3 years | ||
| − | |style="background-color:#1a9850"|Superior PFS | + | | style="background-color:#1a9850" |Superior PFS |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347867/ Kang et al. 2013 (RIGHT)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347867/ Kang et al. 2013 (RIGHT)] | ||
| − | |style="background-color:#1a9851"|Phase III (E) | + | | style="background-color:#1a9851" |Phase III (E) |
|[[#Placebo_2|Placebo]] | |[[#Placebo_2|Placebo]] | ||
| − | |style="background-color:#1a9850"|Superior PFS | + | | style="background-color:#1a9850" |Superior PFS |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521211/ Blay et al. 2015 (ENESTg1)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521211/ Blay et al. 2015 (ENESTg1)] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|Nilotinib | |Nilotinib | ||
| − | |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)] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|Bevacizumab & Imatinib | |Bevacizumab & Imatinib | ||
| − | |style="background-color:#d3d3d3"|Not reported | + | | style="background-color:#d3d3d3" |Not reported |
|- | |- | ||
|} | |} | ||
''Note: Efficacy reported 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.'' | ''Note: Efficacy reported 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.'' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
| + | |||
*[[Imatinib (Gleevec)]] 400 mg PO once per day, taken with food | *[[Imatinib (Gleevec)]] 400 mg PO once per day, taken with food | ||
| Line 246: | Line 266: | ||
===Variant #2, higher-dose (600 mg/day) {{#subobject:304d2f|Variant=1}}=== | ===Variant #2, higher-dose (600 mg/day) {{#subobject:304d2f|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
| − | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
| − | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
|[https://www.nejm.org/doi/full/10.1056/NEJMoa020461 Demetri et al. 2002] | |[https://www.nejm.org/doi/full/10.1056/NEJMoa020461 Demetri et al. 2002] | ||
| − | |style="background-color:#1a9851"|Phase III (E) | + | | style="background-color:#1a9851" |Phase III (E) |
|[[#Imatinib_monotherapy_3|Imatinib]]; standard-dose (400 mg/day) | |[[#Imatinib_monotherapy_3|Imatinib]]; standard-dose (400 mg/day) | ||
| − | |style="background-color:#ffffbf"|Seems not superior | + | | style="background-color:#ffffbf" |Seems not superior |
|- | |- | ||
|} | |} | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
| + | |||
*[[Imatinib (Gleevec)]] 600 mg PO once per day, taken with food | *[[Imatinib (Gleevec)]] 600 mg PO once per day, taken with food | ||
| Line 264: | Line 285: | ||
===Variant #3, high-dose (800 mg/day) {{#subobject:4e83a6|Variant=1}}=== | ===Variant #3, high-dose (800 mg/day) {{#subobject:4e83a6|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
| − | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
| − | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
|[https://www.sciencedirect.com/science/article/pii/S0140673601065357 Van Oosterom et al. 2001] | |[https://www.sciencedirect.com/science/article/pii/S0140673601065357 Van Oosterom et al. 2001] | ||
| Line 280: | Line 301: | ||
|- | |- | ||
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(04)17098-0/fulltext Verweij et al. 2004 (EORTC 62005)] | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(04)17098-0/fulltext Verweij et al. 2004 (EORTC 62005)] | ||
| − | |style="background-color:#1a9851"|Phase III (E-RT) | + | | style="background-color:#1a9851" |Phase III (E-RT) |
|[[#Imatinib_monotherapy_3|Imatinib]]; standard-dose | |[[#Imatinib_monotherapy_3|Imatinib]]; standard-dose | ||
| − | |style="background-color:#ffffbf"|Seems not superior (*) | + | | style="background-color:#ffffbf" |Seems not superior (*) |
|- | |- | ||
|[http://jco.ascopubs.org/content/26/4/626.long Blanke et al. 2008 (SWOG S0033)] | |[http://jco.ascopubs.org/content/26/4/626.long Blanke et al. 2008 (SWOG S0033)] | ||
| − | |style="background-color:#1a9851"|Phase III (E-RT) | + | | style="background-color:#1a9851" |Phase III (E-RT) |
|[[#Imatinib_monotherapy_3|Imatinib]]; standard-dose with pre-planned dose-escalation at progression | |[[#Imatinib_monotherapy_3|Imatinib]]; standard-dose with pre-planned dose-escalation at progression | ||
| − | |style="background-color:#ffffbf"|Seems not superior | + | | style="background-color:#ffffbf" |Seems not superior |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521211/ Blay et al. 2015 (ENESTg1)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521211/ Blay et al. 2015 (ENESTg1)] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|Nilotinib | |Nilotinib | ||
| − | |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)] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|Bevacizumab & Imatinib | |Bevacizumab & Imatinib | ||
| − | |style="background-color:#d3d3d3"|Not reported | + | | style="background-color:#d3d3d3" |Not reported |
|- | |- | ||
|} | |} | ||
''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. Efficacy reported 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. Efficacy reported for EORTC 62005 is based on the 2017 update.'' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
| + | |||
*[[Imatinib (Gleevec)]] 400 mg PO twice a day, taken after a meal | *[[Imatinib (Gleevec)]] 400 mg PO twice a day, taken after a meal | ||
| Line 308: | Line 330: | ||
===Variant #4, standard-dose with pre-planned dose-escalation at progression {{#subobject:854522|Variant=1}}=== | ===Variant #4, standard-dose with pre-planned dose-escalation at progression {{#subobject:854522|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
| − | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
| − | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
|[http://jco.ascopubs.org/content/26/4/626.long Blanke et al. 2008 (SWOG S0033)] | |[http://jco.ascopubs.org/content/26/4/626.long Blanke et al. 2008 (SWOG S0033)] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|[[#Imatinib_monotherapy_3|Imatinib]]; high-dose (800 mg/day) | |[[#Imatinib_monotherapy_3|Imatinib]]; high-dose (800 mg/day) | ||
| − | |style="background-color:#ffffbf"|Seems not superior | + | | style="background-color:#ffffbf" |Seems not superior |
|- | |- | ||
|} | |} | ||
====Chemotherapy, standard-dose==== | ====Chemotherapy, standard-dose==== | ||
| + | |||
*[[Imatinib (Gleevec)]] 400 mg PO once per day | *[[Imatinib (Gleevec)]] 400 mg PO once per day | ||
| Line 327: | Line 350: | ||
====Chemotherapy, high-dose==== | ====Chemotherapy, high-dose==== | ||
| + | |||
*[[Imatinib (Gleevec)]] 400 mg PO twice per day | *[[Imatinib (Gleevec)]] 400 mg PO twice per day | ||
| Line 332: | Line 356: | ||
===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; European Organisation for Research and Treatment of Cancer 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://www.sciencedirect.com/science/article/pii/S0140673601065357 link to SD article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.nejm.org/doi/full/10.1056/NEJMoa020461 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12181401 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; European Organisation for Research and Treatment of Cancer 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://www.sciencedirect.com/science/article/pii/S0140673601065357 link to SD article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11705489 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. 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://www.ejcancer.com/article/S0959-8049%2802%2900836-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12957454 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://www.nejm.org/doi/full/10.1056/NEJMoa020461 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12181401 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(04)17098-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15451219 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. 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://www.ejcancer.com/article/S0959-8049%2802%2900836-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12957454 PubMed] |
| − | ## '''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. [https://www.ejcancer.com/article/S0959-8049(05)00440-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16098458 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(04)17098-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15451219 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; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group and Italian Sarcoma Group and 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://ascopubs.org/doi/full/10.1200/JCO.2016.71.0228 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28362562 PubMed] | + | ##'''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. [https://www.ejcancer.com/article/S0959-8049(05)00440-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16098458 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. 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://ascopubs.org/doi/full/10.1200/JCO.2006.09.0183 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17369574 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; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group and Italian Sarcoma Group and 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://ascopubs.org/doi/full/10.1200/JCO.2016.71.0228 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28362562 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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70222-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20864406 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. 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://ascopubs.org/doi/full/10.1200/JCO.2006.09.0183 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17369574 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. [http://jco.ascopubs.org/content/26/4/626.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18235122 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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70222-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20864406 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834472/ link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834472/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20124181 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. [http://jco.ascopubs.org/content/26/4/626.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18235122 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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70453-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347867/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24140183 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834472/ link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834472/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20124181 PubMed] |
| − | # '''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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70105-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521211/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25882987 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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70453-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347867/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24140183 PubMed] |
| − | # '''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. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679092/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26576593 PubMed] | + | #'''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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70105-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521211/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25882987 PubMed] |
| + | #'''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. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679092/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26576593 PubMed] | ||
==Pazopanib monotherapy {{#subobject:cfbaff|Regimen=1}}== | ==Pazopanib monotherapy {{#subobject:cfbaff|Regimen=1}}== | ||
| Line 354: | Line 379: | ||
===Regimen {{#subobject:1debcd|Variant=1}}=== | ===Regimen {{#subobject:1debcd|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
| − | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
| − | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00075-9/fulltext Mir et al. 2016 (PAZOGIST)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00075-9/fulltext Mir et al. 2016 (PAZOGIST)] | ||
| − | |style="background-color:#1a9851"|Randomized Phase II (E) | + | | style="background-color:#1a9851" |Randomized Phase II (E) |
|[[#Best_supportive_care|Best supportive care]] | |[[#Best_supportive_care|Best supportive care]] | ||
| − | |style="background-color:#91cf60"|Seems to have superior PFS | + | | style="background-color:#91cf60" |Seems to have superior PFS |
|- | |- | ||
|} | |} | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
| + | |||
*[[Pazopanib (Votrient)]] 800 mg PO once per day | *[[Pazopanib (Votrient)]] 800 mg PO once per day | ||
| Line 371: | Line 397: | ||
===References=== | ===References=== | ||
| − | # 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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00075-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27068858 PubMed] | + | |
| + | #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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00075-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27068858 PubMed] | ||
==Placebo== | ==Placebo== | ||
| Line 380: | Line 407: | ||
===Regimen=== | ===Regimen=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
| − | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
| − | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)69446-4/abstract Demetri et al. 2006 (A6181004)] | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)69446-4/abstract Demetri et al. 2006 (A6181004)] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|[[#Sunitinib_monotherapy|Sunitinib]] | |[[#Sunitinib_monotherapy|Sunitinib]] | ||
| − | |style="background-color:#d73027"|Inferior TTP | + | | style="background-color:#d73027" |Inferior TTP |
|- | |- | ||
|[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)] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|[[#Regorafenib_monotherapy|Regorafenib]] | |[[#Regorafenib_monotherapy|Regorafenib]] | ||
| − | |style="background-color:#d73027"|Inferior PFS | + | | style="background-color:#d73027" |Inferior PFS |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347867/ Kang et al. 2013 (RIGHT)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347867/ Kang et al. 2013 (RIGHT)] | ||
| − | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|[[#Imatinib_monotherapy_3|Imatinib]] | |[[#Imatinib_monotherapy_3|Imatinib]] | ||
| − | |style="background-color:#d73027"|Inferior PFS | + | | style="background-color:#d73027" |Inferior PFS |
|- | |- | ||
|} | |} | ||
| Line 404: | Line 431: | ||
===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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)69446-4/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17046465 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://www.ncbi.nlm.nih.gov/pubmed/22661587 PubMed] | + | #'''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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)69446-4/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17046465 PubMed] |
| − | # '''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. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819942/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23177515 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://www.ncbi.nlm.nih.gov/pubmed/22661587 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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70453-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347867/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24140183 PubMed] | + | #'''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. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819942/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23177515 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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70453-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347867/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24140183 PubMed] | ||
==Regorafenib monotherapy {{#subobject:bd09ce|Regimen=1}}== | ==Regorafenib monotherapy {{#subobject:bd09ce|Regimen=1}}== | ||
| Line 417: | Line 445: | ||
===Regimen {{#subobject:6dcadc|Variant=1}}=== | ===Regimen {{#subobject:6dcadc|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
| − | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
| − | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
|[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)] | ||
| − | |style="background-color:#1a9851"|Phase III (E-RT) | + | | style="background-color:#1a9851" |Phase III (E-RT) |
|[[#Placebo_2|Placebo]] | |[[#Placebo_2|Placebo]] | ||
| − | |style="background-color:#1a9850"|Superior PFS | + | | style="background-color:#1a9850" |Superior PFS |
|- | |- | ||
|} | |} | ||
''Patients in this study already had treatment failure with imatinib and sunitinib.'' | ''Patients in this study already had treatment failure with imatinib and sunitinib.'' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
| + | |||
*[[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 | ||
| Line 435: | Line 464: | ||
===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. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819942/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23177515 PubMed] | + | |
| + | #'''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. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819942/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23177515 PubMed] | ||
==Sunitinib monotherapy {{#subobject:ec3261|Regimen=1}}== | ==Sunitinib monotherapy {{#subobject:ec3261|Regimen=1}}== | ||
| Line 445: | Line 475: | ||
===Regimen {{#subobject:38e8e3|Variant=1}}=== | ===Regimen {{#subobject:38e8e3|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
| − | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
| − | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
| − | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
| − | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)69446-4/abstract Demetri et al. 2006 (A6181004)] | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)69446-4/abstract Demetri et al. 2006 (A6181004)] | ||
| − | |style="background-color:#1a9851"|Phase III (E-RT) | + | | style="background-color:#1a9851" |Phase III (E-RT) |
|[[#Placebo_2|Placebo]] | |[[#Placebo_2|Placebo]] | ||
| − | |style="background-color:#1a9850"|Superior TTP | + | | style="background-color:#1a9850" |Superior TTP |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143095/ Adenis et al. 2014] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143095/ Adenis et al. 2014] | ||
| − | |style="background-color:#1a9851"|Randomized Phase II (C) | + | | style="background-color:#1a9851" |Randomized Phase II (C) |
|Masitinib | |Masitinib | ||
| style="background-color:#fc8d59" |Seems to have inferior OS | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
| Line 463: | Line 493: | ||
''Patients had treatment failure with imatinib.'' | ''Patients had treatment failure with imatinib.'' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
| + | |||
*[[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 | ||
| − | **Dose may be decreased to 37.5 mg or 25 mg depending on tolerability | + | **Dose may be decreased to 37.5 mg or 25 mg depending on tolerability |
'''42-day cycles''' | '''42-day cycles''' | ||
===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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)69446-4/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17046465 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://www.ncbi.nlm.nih.gov/pubmed/22661587 PubMed] | + | #'''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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)69446-4/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17046465 PubMed] |
| − | # 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://academic.oup.com/annonc/article/25/9/1762/2801236 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143095/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25122671 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://www.ncbi.nlm.nih.gov/pubmed/22661587 PubMed] |
| + | #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://academic.oup.com/annonc/article/25/9/1762/2801236 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143095/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25122671 PubMed] | ||
| + | |||
| + | == Sorafenib monotherapy == | ||
| + | |||
| + | === Regimen === | ||
| + | {| class="wikitable" style="width: 100%; text-align:center;" | ||
| + | ! style="width: 25%" |Study | ||
| + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
| + | |- | ||
| + | |[https://www.ncbi.nlm.nih.gov/pubmed/22270258 Park et al. 2012] | ||
| + | | style="background-color:#1a9851" |Phase II | ||
| + | |- | ||
| + | |[https://ascopubs.org/doi/abs/10.1200/jco.2011.29.15_suppl.10009 Kindler et al. 2011] | ||
| + | | style="background-color:#1a9851" |Phase II | ||
| + | |} | ||
| + | |||
| + | ==== Chemotherapy ==== | ||
| + | |||
| + | * Sorafenib (Nexavar) 400mg PO BID until disease progression or intolerance | ||
| + | |||
| + | === References === | ||
| + | |||
| + | # Park SH, Ryu MH, Ryoo BY, Im SA, Kwon HC, Lee SS, Park SR, Kang BY, Kang YK. 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 | ||
| + | # 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. ''29 (15_suppl) 10009-10009.'' | ||
[[Category:Gastrointestinal stromal tumor regimens]] | [[Category:Gastrointestinal stromal tumor regimens]] | ||
Revision as of 14:46, 25 September 2019
11 regimens on this page
15 variants on this page
|
Guidelines
ESMO
- 2014: Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
ESMO/EURACAN
- 2018: Casali et al. Gastrointestinal stromal tumours: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up
NCCN
Neoadjuvant therapy
Imatinib monotherapy
| back to top |
Regimen
| Study | Evidence |
|---|---|
| Eisenberg et al. 2009 (RTOG 0132) | Phase II |
Chemotherapy
- Imatinib (Gleevec) 600 mg PO once per day
28-day cycle for 2 to 3 cycles; stopped on the day prior to surgery
Subsequent 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. contains verified protocol 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 PMC article PubMed
Adjuvant therapy
Imatinib monotherapy
| back to top |
Variant #1, 12 months of treatment
| FDA-recommended dose |
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Dematteo et al. 2009 (ACOSOG Z9001) | Phase III (E-RT) | Placebo | Superior RFS |
| Joensuu et al. 2012 (SSG XVIII/AIO) | Phase III (C) | Imatinib x 36 mos | Seems to have inferior OS |
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.
Preceding treatment
Chemotherapy
- Imatinib (Gleevec) 400 mg PO once per day
12-month course
Variant #2, 2 years of treatment
| Study | Evidence |
|---|---|
| Eisenberg et al. 2009 (RTOG 0132) | Phase II |
Preceding treatment
- Neoadjuvant imatinib, then Surgery
Chemotherapy
- Imatinib (Gleevec) 600 mg PO once per day
2-year course
Variant #3, 3 years of treatment
| FDA-recommended dose |
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Joensuu et al. 2012 (SSG XVIII/AIO) | Phase III (E) | Imatinib x 12 mos | Seems to have superior OS |
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.
Preceding treatment
Chemotherapy
- Imatinib (Gleevec) 400 mg PO once per day
36-month course
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. contains verified protocol 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 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 (ACOSOG) Intergroup Adjuvant GIST Study Team. 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. link to original article contains verified protocol link to PMC article PubMed
- 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 verified protocol 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. link to original article PubMed
Placebo
| back to top |
Regimen
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Dematteo et al. 2009 (ACOSOG Z9001) | Phase III (C) | Imatinib x 12 mos | Inferior RFS |
No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.
Preceding treatment
References
- 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 (ACOSOG) Intergroup Adjuvant GIST Study Team. 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. contains verified protocol link to PMC article PubMed
Metastatic or unresectable disease
Best supportive care
| back to top |
Regimen
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Reichardt et al. 2012 (ENEST g3) | Phase III (C) | Nilotinib | Seems not superior |
| Mir et al. 2016 (PAZOGIST) | Randomized Phase II (C) | Pazopanib | Seems to have inferior PFS |
No active treatment. Used as a comparator arm and here for reference purposes only.
References
- ENEST g3: Reichardt P, Blay JY, Gelderblom H, Schlemmer M, Demetri GD, Bui-Nguyen B, McArthur GA, Yazji S, Hsu Y, Galetic I, Rutkowski P. Phase III study of nilotinib versus best supportive care with or without a TKI in patients with gastrointestinal stromal tumors resistant to or intolerant of imatinib and sunitinib. Ann Oncol. 2012 Jul;23(7):1680-7. Epub 2012 Feb 21. link to original article PubMed
- 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 protocol PubMed
Imatinib monotherapy
| back to top |
Variant #1, standard-dose (400 mg/day)
| FDA-recommended dose |
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Demetri et al. 2002 | Phase III (C) | Imatinib; higher-dose (600 mg/day) | Seems not superior |
| Verweij et al. 2004 (EORTC 62005) | Phase III (C) | Imatinib; high-dose | Seems not superior (*) |
| Blay et al. 2007 (BFR14) | Phase III (C) | 1. Imatinib; 1 year 2. Imatinib; 3 years |
Superior PFS |
| Kang et al. 2013 (RIGHT) | Phase III (E) | Placebo | Superior PFS |
| Blay et al. 2015 (ENESTg1) | Phase III (C) | Nilotinib | Superior PFS |
| Blanke et al. 2015 (SWOG S0502) | Phase III (C) | Bevacizumab & Imatinib | Not reported |
Note: Efficacy reported 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.
Chemotherapy
- Imatinib (Gleevec) 400 mg PO once per day, taken with food
Continued indefinitely
Variant #2, higher-dose (600 mg/day)
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Demetri et al. 2002 | Phase III (E) | Imatinib; standard-dose (400 mg/day) | Seems not superior |
Chemotherapy
- Imatinib (Gleevec) 600 mg PO once per day, taken with food
Continued indefinitely
Variant #3, high-dose (800 mg/day)
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Van Oosterom et al. 2001 | Phase 1, <20 pts in this cohort | ||
| Verweij et al. 2003 | Phase II | ||
| Verweij et al. 2004 (EORTC 62005) | Phase III (E-RT) | Imatinib; standard-dose | Seems not superior (*) |
| Blanke et al. 2008 (SWOG S0033) | Phase III (E-RT) | Imatinib; standard-dose with pre-planned dose-escalation at progression | Seems not superior |
| Blay et al. 2015 (ENESTg1) | Phase III (C) | Nilotinib | Superior PFS |
| Blanke et al. 2015 (SWOG S0502) | Phase III (C) | Bevacizumab & Imatinib | Not reported |
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. Efficacy reported for EORTC 62005 is based on the 2017 update.
Chemotherapy
- Imatinib (Gleevec) 400 mg PO twice a day, taken after a meal
Continued indefinitely
Variant #4, standard-dose with pre-planned dose-escalation at progression
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Blanke et al. 2008 (SWOG S0033) | Phase III (C) | Imatinib; high-dose (800 mg/day) | Seems not superior |
Chemotherapy, standard-dose
- Imatinib (Gleevec) 400 mg PO once per day
Continued indefinitely
Patients who progressed could receive high-dose therapy, as follows:
Chemotherapy, high-dose
- 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; European Organisation for Research and Treatment of Cancer 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 SD article contains protocol 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 verified protocol 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. 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 verified protocol 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 protocol PubMed
- 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; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group and Italian Sarcoma Group and 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. 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 protocol 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. link to original article contains protocol 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 verified protocol 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 verified protocol PubMed
- 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 verified protocol PubMed
- 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. contains verified protocol link to PMC article PubMed
Pazopanib monotherapy
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Regimen
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Mir et al. 2016 (PAZOGIST) | Randomized Phase II (E) | Best supportive care | Seems to have superior PFS |
Chemotherapy
- Pazopanib (Votrient) 800 mg PO once per day
Continued indefinitely
References
- 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 protocol PubMed
Placebo
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Regimen
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Demetri et al. 2006 (A6181004) | Phase III (C) | Sunitinib | Inferior TTP |
| Demetri et al. 2012 (GRID) | Phase III (C) | Regorafenib | Inferior PFS |
| Kang et al. 2013 (RIGHT) | Phase III (C) | Imatinib | Inferior PFS |
No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.
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 verified protocol 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. link to original article link to PMC article PubMed
- 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. contains verified protocol 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 verified protocol PubMed
Regorafenib monotherapy
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Regimen
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Demetri et al. 2012 (GRID) | Phase III (E-RT) | Placebo | Superior PFS |
Patients in this study already had treatment failure with imatinib and sunitinib.
Chemotherapy
- Regorafenib (Stivarga) 160 mg PO once per day on days 1 to 21
28-day cycles
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. contains verified protocol link to PMC article PubMed
Sunitinib monotherapy
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Regimen
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Demetri et al. 2006 (A6181004) | Phase III (E-RT) | Placebo | Superior TTP |
| Adenis et al. 2014 | Randomized Phase II (C) | Masitinib | Seems to have inferior OS |
Patients had treatment failure with imatinib.
Chemotherapy
- Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28
- Dose may be decreased to 37.5 mg or 25 mg depending on tolerability
42-day cycles
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 verified protocol 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. link to original article link to PMC article PubMed
- 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
Sorafenib monotherapy
Regimen
| Study | Evidence |
|---|---|
| Park et al. 2012 | Phase II |
| Kindler et al. 2011 | Phase II |
Chemotherapy
- Sorafenib (Nexavar) 400mg PO BID until disease progression or intolerance
References
- Park SH, Ryu MH, Ryoo BY, Im SA, Kwon HC, Lee SS, Park SR, Kang BY, Kang YK. 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
- 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. 29 (15_suppl) 10009-10009.