Difference between revisions of "Gastrointestinal stromal tumor"
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## '''Update:''' Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hermes B, Schütte J, Cameron S, Hohenberger P, Jost PJ, Al-Batran SE, Lindner LH, Bauer S, Wardelmann E, Nilsson B, Kallio R, Jaakkola P, Junnila J, Alvegård T, Reichardt P. Survival Outcomes Associated With 3 Years vs 1 Year of Adjuvant Imatinib for Patients With High-Risk Gastrointestinal Stromal Tumors: An Analysis of a Randomized Clinical Trial After 10-Year Follow-up. JAMA Oncol. 2020 Aug 1;6(8):1241-1246. [https://doi.org/10.1001/jamaoncol.2020.2091 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260691/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32469385/ PubMed] | ## '''Update:''' Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hermes B, Schütte J, Cameron S, Hohenberger P, Jost PJ, Al-Batran SE, Lindner LH, Bauer S, Wardelmann E, Nilsson B, Kallio R, Jaakkola P, Junnila J, Alvegård T, Reichardt P. Survival Outcomes Associated With 3 Years vs 1 Year of Adjuvant Imatinib for Patients With High-Risk Gastrointestinal Stromal Tumors: An Analysis of a Randomized Clinical Trial After 10-Year Follow-up. JAMA Oncol. 2020 Aug 1;6(8):1241-1246. [https://doi.org/10.1001/jamaoncol.2020.2091 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260691/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32469385/ PubMed] | ||
− | =Metastatic or unresectable disease | + | =Metastatic or unresectable disease, all lines of therapy= |
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==Imatinib monotherapy {{#subobject:16a4ba|Regimen=1}}== | ==Imatinib monotherapy {{#subobject:16a4ba|Regimen=1}}== | ||
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#'''SWOG S0502:''' Blanke CD, Rankin C, Corless C, Eary JF, Mulder K, Okuno SH, George S, Heinrich M. S0502: A SWOG phase III randomized study of imatinib, with or without bevacizumab, in patients with untreated metastatic or unresectable gastrointestinal stromal tumors. Oncologist. 2015 Dec;20(12):1353-4. Epub 2015 Nov 17. [https://doi.org/10.1634/theoncologist.2015-0295 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679092/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26576593 PubMed] NCT00324987 | #'''SWOG S0502:''' Blanke CD, Rankin C, Corless C, Eary JF, Mulder K, Okuno SH, George S, Heinrich M. S0502: A SWOG phase III randomized study of imatinib, with or without bevacizumab, in patients with untreated metastatic or unresectable gastrointestinal stromal tumors. Oncologist. 2015 Dec;20(12):1353-4. Epub 2015 Nov 17. [https://doi.org/10.1634/theoncologist.2015-0295 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679092/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26576593 PubMed] NCT00324987 | ||
− | + | =Metastatic or unresectable disease, second-line= | |
− | + | ''Most trials define this context as imatinib-resistant.'' | |
==Linsitinib monotherapy {{#subobject:cfbaff|Regimen=1}}== | ==Linsitinib monotherapy {{#subobject:cfbaff|Regimen=1}}== | ||
{| class="wikitable" style="float:right; margin-left: 5px;" | {| class="wikitable" style="float:right; margin-left: 5px;" | ||
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#'''SARC 022:''' Von Mehren M, George S, Heinrich M, Schuetze S, Yap J, Yu J, Abbott A, Litwin S, Crowley J, Belinsky M, Janeway K, Hornick J, Flieder D, Chugh R, Rink L, Van den Abbeele A. Linsitinib (OSI-906) for the Treatment of Adult and Pediatric Wild-Type Gastrointestinal Stromal Tumors: a SARC Phase II Study. Clin Cancer Res. 2020 April; 15;26(8):1837-1845. Epub 2019 Dec 2. [https://clincancerres.aacrjournals.org/content/26/8/1837.long link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7856429/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/31792037/ PubMed] NCT01560260 | #'''SARC 022:''' Von Mehren M, George S, Heinrich M, Schuetze S, Yap J, Yu J, Abbott A, Litwin S, Crowley J, Belinsky M, Janeway K, Hornick J, Flieder D, Chugh R, Rink L, Van den Abbeele A. Linsitinib (OSI-906) for the Treatment of Adult and Pediatric Wild-Type Gastrointestinal Stromal Tumors: a SARC Phase II Study. Clin Cancer Res. 2020 April; 15;26(8):1837-1845. Epub 2019 Dec 2. [https://clincancerres.aacrjournals.org/content/26/8/1837.long link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7856429/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/31792037/ PubMed] NCT01560260 | ||
+ | |||
+ | ==Sunitinib monotherapy {{#subobject:ec3261|Regimen=1}}== | ||
+ | {| class="wikitable" style="float:right; margin-left: 5px;" | ||
+ | |- | ||
+ | |[[#top|back to top]] | ||
+ | |} | ||
+ | |||
+ | ===Regimen {{#subobject:38e8e3|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Years of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)69446-4/abstract Demetri et al. 2006 (A6181004)] | ||
+ | |2003-2005 | ||
+ | | style="background-color:#1a9851" |Phase III (E-RT-esc) | ||
+ | |[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo_2|Placebo]] | ||
+ | | style="background-color:#1a9850" |Superior TTP | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143095/ Adenis et al. 2014 (AB07001)] | ||
+ | |2009-2011 | ||
+ | | style="background-color:#1a9851" |Randomized Phase II (C) | ||
+ | |Masitinib | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | ====Targeted therapy==== | ||
+ | |||
+ | *[[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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)69446-4/abstract link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/17046465 PubMed] NCT00075218 | ||
+ | ##'''Update:''' Demetri GD, Garrett CR, Schöffski P, Shah MH, Verweij J, Leyvraz S, Hurwitz HI, Pousa AL, Le Cesne A, Goldstein D, Paz-Ares L, Blay JY, McArthur GA, Xu QC, Huang X, Harmon CS, Tassell V, Cohen DP, Casali PG. Complete longitudinal analyses of the randomized, placebo-controlled, phase III trial of sunitinib in patients with gastrointestinal stromal tumor following imatinib failure. Clin Cancer Res. 2012 Jun 1;18(11):3170-9. [https://clincancerres.aacrjournals.org/content/18/11/3170.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030710/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22661587 PubMed] | ||
+ | #'''AB07001:''' Adenis A, Blay JY, Bui-Nguyen B, Bouché O, Bertucci F, Isambert N, Bompas E, Chaigneau L, Domont J, Ray-Coquard I, Blésius A, Van Tine BA, Bulusu VR, Dubreuil P, Mansfield CD, Acin Y, Moussy A, Hermine O, Le Cesne A. Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial. Ann Oncol. 2014 Sep;25(9):1762-9. Epub 2014 Jul 25. [https://doi.org/10.1093/annonc/mdu237 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143095/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25122671 PubMed] NCT01506336 | ||
+ | #'''AB11002:''' NCT01694277 | ||
+ | |||
+ | =Metastatic or unresectable disease, third-line= | ||
+ | ''Most trials define this context as imatinib- and sunitinib-resistant.'' | ||
+ | ==Cabozantinib monotherapy {{#subobject:s9nxm1|Regimen=1}}== | ||
+ | {| class="wikitable" style="float:right; margin-left: 5px;" | ||
+ | |- | ||
+ | |[[#top|back to top]] | ||
+ | |} | ||
+ | ===Regimen {{#subobject:8c0u8g|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Years of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.ejca.2020.04.021 Schöffski et al. 2020 (CaboGIST)] | ||
+ | |2017-2018 | ||
+ | | style="background-color:#91cf61" |Phase II | ||
+ | |- | ||
+ | |} | ||
+ | ====Targeted therapy==== | ||
+ | *[[Cabozantinib (Cometriq)]] 60 mg PO once per day | ||
+ | |||
+ | '''28-day cycles''' | ||
+ | |||
+ | ===References=== | ||
+ | #'''CaboGIST:''' Schöffski P, Mir O, Kasper B, Papai Z, Blay JY, Italiano A, Benson C, Kopeckova K, Ali N, Dileo P, LeCesne A, Menge F, Cousin S, Wardelmann E, Wozniak A, Marreaud S, Litiere S, Zaffaroni F, Nzokirantevye A, Vanden Bempt I, Gelderblom H. Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 'CaboGIST'. Eur J Cancer. 2020 Jul;134:62-74. Epub 2020 May 26. [https://doi.org/10.1016/j.ejca.2020.04.021 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/32470848/ PubMed] NCT02216578 | ||
==Pazopanib monotherapy {{#subobject:cfbaff|Regimen=1}}== | ==Pazopanib monotherapy {{#subobject:cfbaff|Regimen=1}}== | ||
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#'''GRID:''' Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Schöffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG; GRID study investigators. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):295-302. Epub 2012 Nov 22. [https://doi.org/10.1016/s0140-6736(12)61857-1 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819942/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23177515 PubMed] NCT01271712 | #'''GRID:''' Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Schöffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG; GRID study investigators. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):295-302. Epub 2012 Nov 22. [https://doi.org/10.1016/s0140-6736(12)61857-1 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819942/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23177515 PubMed] NCT01271712 | ||
#'''VOYAGER:''' Kang YK, George S, Jones RL, Rutkowski P, Shen L, Mir O, Patel S, Zhou Y, von Mehren M, Hohenberger P, Villalobos V, Brahmi M, Tap WD, Trent J, Pantaleo MA, Schöffski P, He K, Hew P, Newberry K, Roche M, Heinrich MC, Bauer S. Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study. J Clin Oncol. 2021 Oct 1;39(28):3128-3139. Epub 2021 Aug 3. [https://doi.org/10.1200/jco.21.00217 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478403/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34343033/ PubMed] NCT03465722 | #'''VOYAGER:''' Kang YK, George S, Jones RL, Rutkowski P, Shen L, Mir O, Patel S, Zhou Y, von Mehren M, Hohenberger P, Villalobos V, Brahmi M, Tap WD, Trent J, Pantaleo MA, Schöffski P, He K, Hew P, Newberry K, Roche M, Heinrich MC, Bauer S. Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study. J Clin Oncol. 2021 Oct 1;39(28):3128-3139. Epub 2021 Aug 3. [https://doi.org/10.1200/jco.21.00217 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478403/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34343033/ PubMed] NCT03465722 | ||
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==Sorafenib monotherapy {{#subobject:ec8ga1|Regimen=1}}== | ==Sorafenib monotherapy {{#subobject:ec8ga1|Regimen=1}}== | ||
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#'''SMC 2009-08-102:''' Park SH, Ryu MH, Ryoo BY, Im SA, Kwon HC, Lee SS, Park SR, Kang BY, Kang YK; Korean gastrointestinal stromal tumors study group. Sorafenib in patients with metastatic gastrointestinal stromal tumors who failed two or more prior tyrosine kinase inhibitors: a phase II study of Korean gastrointestinal stromal tumors study group. Invest New Drugs. 2012 Dec; 30(6) 2377-83. Epub 2012 Jan 25. [https://doi.org/10.1007/s10637-012-9795-9 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/22270258 PubMed] NCT01091207 | #'''SMC 2009-08-102:''' Park SH, Ryu MH, Ryoo BY, Im SA, Kwon HC, Lee SS, Park SR, Kang BY, Kang YK; Korean gastrointestinal stromal tumors study group. Sorafenib in patients with metastatic gastrointestinal stromal tumors who failed two or more prior tyrosine kinase inhibitors: a phase II study of Korean gastrointestinal stromal tumors study group. Invest New Drugs. 2012 Dec; 30(6) 2377-83. Epub 2012 Jan 25. [https://doi.org/10.1007/s10637-012-9795-9 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/22270258 PubMed] NCT01091207 | ||
− | == | + | =Metastatic or unresectable disease, fourth-line= |
+ | ''Many trials define this context as imatinib-, sunitinib-, and regorafenib-resistant.'' | ||
+ | ==Avapritinib monotherapy {{#subobject:16ab1a|Regimen=1}}== | ||
+ | |||
+ | ===Regimen {{#subobject:q8bx4b|Variant=1}}=== | ||
+ | {| class="wikitable" style="color:white; background-color:#404040" | ||
+ | |<small>'''FDA-recommended dose'''</small> | ||
+ | |} | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Years of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(20)30269-2 Heinrich et al. 2020 (NAVIGATOR)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#ffffbe" |Phase I (RT) | ||
+ | |} | ||
+ | ''Note: Patients in this study either had the PDGFRA D842V mutation or already had treatment failure with imatinib and ≥1 additional tyrosine kinase inhibitor. This is the recommended phase II dose.'' | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | |||
+ | *Gene: PDGFRA | ||
+ | *Alteration: D842V | ||
+ | |||
+ | ====Chemotherapy==== | ||
+ | [[Avapritinib (Ayvakit)]] 300 mg PO once per day on an empty stomach (at least 1 hour before and 2 hours after a meal) | ||
+ | |||
+ | '''Continued indefinitely''' | ||
+ | |||
+ | ===References=== | ||
+ | |||
+ | <!-- #'''Abstract:''' Heinrich MC, Jones RL, Von Mehren M, Bauer S, Kang YK, Schoffski P, Eskens F, Mir O, Cassier PA, Serrano C, Tap WD, Trent JC, Rutkowski P, Patel S, Chawla SP, Meiri E, Zhou T, Mamlouk KK, Roche M, George S. Clinical activity of avapritinib in ≥ fourth-line (4L+) and PDGFRA Exon 18 gastrointestinal stromal tumors (GIST). J Clin Oncol. 2019 May 20. [https://doi.org/10.1200/JCO.2019.37.15_suppl.11022 link to abstract] --> | ||
+ | #'''NAVIGATOR:''' Heinrich MC, Jones RL, von Mehren M, Schöffski P, Serrano C, Kang YK, Cassier PA, Mir O, Eskens F, Tap WD, Rutkowski P, Chawla SP, Trent J, Tugnait M, Evans EK, Lauz T, Zhou T, Roche M, Wolf BB, Bauer S, George S. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020 Jul;21(7):935-946. Erratum in: Lancet Oncol. 2020 Sep;21(9):e418. [https://doi.org/10.1016/s1470-2045(20)30269-2 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/32615108/ PubMed] NCT02508532 | ||
+ | |||
+ | ==Ripretinib monotherapy {{#subobject:bd11ce|Regimen=1}}== | ||
{| class="wikitable" style="float:right; margin-left: 5px;" | {| class="wikitable" style="float:right; margin-left: 5px;" | ||
|- | |- | ||
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|} | |} | ||
− | ===Regimen {{#subobject: | + | ===Regimen {{#subobject:6dugic|Variant=1}}=== |
+ | {| class="wikitable" style="color:white; background-color:#404040" | ||
+ | |<small>'''FDA-recommended dose'''</small> | ||
+ | |- | ||
+ | |} | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
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! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/s1470-2045(20)30168-6 Blay et al. 2020 (INVICTUS)] |
− | | | + | |2018 |
| style="background-color:#1a9851" |Phase III (E-RT-esc) | | style="background-color:#1a9851" |Phase III (E-RT-esc) | ||
|[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo_2|Placebo]] | |[[Gastrointestinal_stromal_tumor_-_null_regimens#Placebo_2|Placebo]] | ||
− | | style="background-color:#1a9850" |Superior | + | | style="background-color:#1a9850" |Superior PFS |
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|- | |- | ||
|} | |} | ||
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====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[ | + | *[[Ripretinib (Qinlock)]] 150 mg PO once per day |
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− | ''' | + | '''Continued indefinitely''' |
===References=== | ===References=== | ||
− | #''' | + | #'''INVICTUS:''' Blay JY, Serrano C, Heinrich MC, Zalcberg J, Bauer S, Gelderblom H, Schöffski P, Jones RL, Attia S, D'Amato G, Chi P, Reichardt P, Meade J, Shi K, Ruiz-Soto R, George S, von Mehren M. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jul;21(7):923-934. Epub 2020 Jun 5. Erratum in: Lancet Oncol. 2020 Jul;21(7):e341. [https://doi.org/10.1016/s1470-2045(20)30168-6 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/32511981 PubMed] NCT03353753 |
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[[Category:Gastrointestinal stromal tumor regimens]] | [[Category:Gastrointestinal stromal tumor regimens]] |
Revision as of 15:06, 28 November 2021
Page editor | Section editor | ||
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Eric Marks, MD Boston University Boston, MA |
Elizabeth J. Davis, MD Vanderbilt University Nashville, TN ejdavis25 |
Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
11 regimens on this page
15 variants on this page
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Guidelines
ESMO/EURACAN
- 2018: Casali et al. Gastrointestinal stromal tumours: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up
Older
- 2014: Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
NCCN
Neoadjuvant therapy
Imatinib monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Eisenberg et al. 2009 (RTOG 0132) | 2002-2006 | Phase II |
Biomarker eligibility criteria
- Kit (CD117) positive
Targeted therapy
- Imatinib (Gleevec) 600 mg PO once per day
28-day cycle for 2 to 3 cycles; stopped on the day prior to surgery
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. link to original article 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 original article link to PMC article PubMed
Adjuvant therapy
Imatinib monotherapy
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Regimen variant #1, 12 months of treatment
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
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Dematteo et al. 2009 (ACOSOG Z9001) | 2002-2007 | Phase III (E-RT-esc) | Placebo | Superior RFS |
Joensuu et al. 2012 (SSG XVIII/AIO) | 2004-2008 | Phase III (C) | Imatinib x 36 mos | Inferior OS1 |
1Reported efficacy for SSG XVIII/AIO is based on the 2020 update.
Treatment is started within 12 weeks after surgery. While this is the FDA-recommended dose, it is noted that the optimal treatment duration is unknown.
Biomarker eligibility criteria
- Kit (CD117) positive
Preceding treatment
Targeted therapy
- Imatinib (Gleevec) 400 mg PO once per day
12-month course
Regimen variant #2, 2 years of treatment
Study | Years of enrollment | Evidence |
---|---|---|
Eisenberg et al. 2009 (RTOG 0132) | 2002-2006 | Phase II |
Biomarker eligibility criteria
- Kit (CD117) positive
Preceding treatment
- Neoadjuvant imatinib, then Surgery
Targeted therapy
- Imatinib (Gleevec) 600 mg PO once per day
2-year course
Regimen variant #3, 3 years of treatment
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Joensuu et al. 2012 (SSG XVIII/AIO) | 2004-2008 | Phase III (E-RT-esc) | Imatinib x 12 mos | Superior OS1 (HR 0.55, 95% CI 0.37-0.83) |
1Reported efficacy is based on the 2020 update.
Treatment is to be started within 12 weeks after surgery. While this is the FDA-recommended dose, it is noted that the optimal treatment duration is unknown.
Biomarker eligibility criteria
- Kit (CD117) positive
Preceding treatment
Targeted therapy
- 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. link to original article 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 original article link to PMC article PubMed
- ACOSOG Z9001: Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K; American College of Surgeons Oncology Group. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Mar 28;373(9669):1097-104. Epub 2009 Mar 18. link to original article contains verified protocol link to PMC article PubMed NCT00041197
- SSG XVIII/AIO: Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schütte J, Ramadori G, Hohenberger P, Duyster J, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Sarlomo-Rikala M, Nilsson B, Sihto H, Monge OR, Bono P, Kallio R, Vehtari A, Leinonen M, Alvegård T, Reichardt P. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA. 2012 Mar 28;307(12):1265-72. link to original article contains verified protocol PubMed NCT00116935
- Update: Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hartmann JT, Pink D, Ramadori G, Hohenberger P, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Nilsson B, Sihto H, Bono P, Kallio R, Junnila J, Alvegård T, Reichardt P. Adjuvant imatinib for high-risk GI stromal tumor: analysis of a randomized trial. J Clin Oncol. 2016 Jan 20;34(3):244-50. Epub 2015 Nov 2. link to original article PubMed
- Update: Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hermes B, Schütte J, Cameron S, Hohenberger P, Jost PJ, Al-Batran SE, Lindner LH, Bauer S, Wardelmann E, Nilsson B, Kallio R, Jaakkola P, Junnila J, Alvegård T, Reichardt P. Survival Outcomes Associated With 3 Years vs 1 Year of Adjuvant Imatinib for Patients With High-Risk Gastrointestinal Stromal Tumors: An Analysis of a Randomized Clinical Trial After 10-Year Follow-up. JAMA Oncol. 2020 Aug 1;6(8):1241-1246. link to original article link to PMC article PubMed
Metastatic or unresectable disease, all lines of therapy
Imatinib monotherapy
back to top |
Regimen variant #1, standard-dose (400 mg/day)
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Demetri et al. 2002 | 2000-2001 | Phase III (C) | Imatinib; higher-dose (600 mg/day) | Did not meet primary endpoint of ORR |
Verweij et al. 2004 (EORTC 62005) | 2001-2002 | Phase III (C) | Imatinib; high-dose | Did not meet primary endpoint of PFS1 |
Blay et al. 2007 (BFR14) | 2002-2004 | Phase III (C) | 1. Imatinib; 1 year 2. Imatinib; 3 years |
Superior PFS |
Blanke et al. 2015 (SWOG S0502) | 2008-2009 | Phase III (C) | Bevacizumab & Imatinib | Not reported |
Blay et al. 2015 (ENESTg1) | 2009-2011 | Phase III (C) | Nilotinib | Superior PFS |
Kang et al. 2013 (RIGHT) | 2010-2013 | Phase III (E-esc) | Placebo | Superior PFS |
1Reported efficacy for EORTC 62005 is based on the 2017 update.
BFR14 had two separate comparisons, to one year and to three years of imatinib versus continuous (this arm); the efficacy outcome was the same in both reports.
Targeted therapy
- Imatinib (Gleevec) 400 mg PO once per day, taken with food
Continued indefinitely
Regimen variant #2, higher-dose (600 mg/day)
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Demetri et al. 2002 | 2000-2001 | Phase III (E-esc) | Imatinib; standard-dose (400 mg/day) | Did not meet primary endpoint of ORR |
Targeted therapy
- Imatinib (Gleevec) 600 mg PO once per day, taken with food
Continued indefinitely
Regimen variant #3, high-dose (800 mg/day)
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Van Oosterom et al. 2001 | 2000 | Phase 1, <20 pts in this cohort | ||
Verweij et al. 2003 | NR | Phase II | ||
Verweij et al. 2004 (EORTC 62005) | 2001-2002 | Phase III (E-RT-esc) | Imatinib; standard-dose | Did not meet primary endpoint of PFS1 |
Blanke et al. 2008 (SWOG S0033) | 2001-2002 | Phase III (E-RT-esc) | Imatinib; standard-dose with pre-planned dose-escalation at progression | Did not meet primary endpoints of PFS/OS |
Blanke et al. 2015 (SWOG S0502) | 2008-2009 | Phase III (C) | Bevacizumab & Imatinib | Not reported |
Blay et al. 2015 (ENESTg1) | 2009-2011 | Phase III (C) | Nilotinib | Superior PFS |
1Reported efficacy for EORTC 62005 is based on the 2017 update.
Note: this was the MTD in Van Oosterom et al. 2001. In some studies, high-dose imatinib was offered to patients with KIT exon 9 mutations in ENESTg1 and SWOG S0502; all other patients received standard-dose imatinib.
Targeted therapy
- Imatinib (Gleevec) 400 mg PO twice a day, taken after a meal
Continued indefinitely
Protocol variant #4, standard-dose with pre-planned dose-escalation at progression
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Blanke et al. 2008 (SWOG S0033) | 2001-2002 | Phase III (C) | Imatinib; high-dose (800 mg/day) | Did not meet primary endpoints of PFS/OS |
Targeted therapy
- Imatinib (Gleevec) 400 mg PO once per day
Continued indefinitely
Patients who progressed could receive high-dose therapy, as follows:
Targeted therapy
- Imatinib (Gleevec) 400 mg PO twice per day
Continued indefinitely
References
- Phase 1: van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, Martens M, Webb A, Sciot R, Van Glabbeke M, Silberman S, Nielsen OS; EORTC Soft Tissue and Bone Sarcoma Group. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet. 2001 Oct 27;358(9291):1421-3. link to original article contains 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; EORTC Soft Tissue and Bone Sarcoma Group. Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target: results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study. Eur J Cancer. 2003 Sep;39(14):2006-11. link to original article contains 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 NCT00685828
- Update: Zalcberg JR, Verweij J, Casali PG, Le Cesne A, Reichardt P, Blay JY, Schlemmer M, Van Glabbeke M, Brown M, Judson IR; EORTC Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian Gastrointestinal Trials Group. Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg. Eur J Cancer. 2005 Aug;41(12):1751-7. link to original article PubMed
- Update: Casali PG, Zalcberg J, Le Cesne A, Reichardt P, Blay JY, Lindner LH, Judson IR, Schöffski P, Leyvraz S, Italiano A, Grünwald V, Pousa AL, Kotasek D, Sleijfer S, Kerst JM, Rutkowski P, Fumagalli E, Hogendoorn P, Litière S, Marreaud S, van der Graaf W, Gronchi A, Verweij J; EORTC Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian Gastrointestinal Trials Group. Ten-year progression-free and overall survival in patients with unresectable or metastatic GI stromal tumors: long-term analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group intergroup phase III randomized trial on imatinib at two dose levels. J Clin Oncol. 2017 May 20;35(15):1713-1720. Epub 2017 Mar 31. link to original article PubMed
- BFR14: Blay JY, Le Cesne A, Ray-Coquard I, Bui B, Duffaud F, Delbaldo C, Adenis A, Viens P, Rios M, Bompas E, Cupissol D, Guillemet C, Kerbrat P, Fayette J, Chabaud S, Berthaud P, Perol D; French Sarcoma Group. Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol. 2007 Mar 20;25(9):1107-13. link to original article contains protocol PubMed NCT00367861
- Update: Le Cesne A, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Cioffi A, Emile JF, Chabaud S, Pérol D, Blay JY; French Sarcoma Group. Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol. 2010 Oct;11(10):942-9. Epub 2010 Sep 21. link to original article contains 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 NCT00009906
- 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 NCT01151852
- ENESTg1: Blay JY, Shen L, Kang YK, Rutkowski P, Qin S, Nosov D, Wan D, Trent J, Srimuninnimit V, Pápai Z, Le Cesne A, Novick S, Taningco L, Mo S, Green S, Reichardt P, Demetri GD. Nilotinib versus imatinib as first-line therapy for patients with unresectable or metastatic gastrointestinal stromal tumours (ENESTg1): a randomised phase 3 trial. Lancet Oncol. 2015 May;16(5):550-60. Epub 2015 Apr 14. link to original article link to PMC article contains verified protocol PubMed NCT00785785
- SWOG S0502: Blanke CD, Rankin C, Corless C, Eary JF, Mulder K, Okuno SH, George S, Heinrich M. S0502: A SWOG phase III randomized study of imatinib, with or without bevacizumab, in patients with untreated metastatic or unresectable gastrointestinal stromal tumors. Oncologist. 2015 Dec;20(12):1353-4. Epub 2015 Nov 17. link to original article contains verified protocol link to PMC article PubMed NCT00324987
Metastatic or unresectable disease, second-line
Most trials define this context as imatinib-resistant.
Linsitinib monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Von Mehren et al. 2019 (SARC 022) | 2012-2013 | Phase II |
Patients in this study had wild-type GIST and had previously failed treatment with at least one prior TKI
Targeted therapy
- Linsitinib (OSI-906) 150 mg PO twice per day
28-day cycles
References
- SARC 022: Von Mehren M, George S, Heinrich M, Schuetze S, Yap J, Yu J, Abbott A, Litwin S, Crowley J, Belinsky M, Janeway K, Hornick J, Flieder D, Chugh R, Rink L, Van den Abbeele A. Linsitinib (OSI-906) for the Treatment of Adult and Pediatric Wild-Type Gastrointestinal Stromal Tumors: a SARC Phase II Study. Clin Cancer Res. 2020 April; 15;26(8):1837-1845. Epub 2019 Dec 2. link to original article link to PMC article contains verified protocol PubMed NCT01560260
Sunitinib monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Demetri et al. 2006 (A6181004) | 2003-2005 | Phase III (E-RT-esc) | Placebo | Superior TTP |
Adenis et al. 2014 (AB07001) | 2009-2011 | Randomized Phase II (C) | Masitinib | Seems to have inferior OS |
Targeted therapy
- 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 NCT00075218
- Update: Demetri GD, Garrett CR, Schöffski P, Shah MH, Verweij J, Leyvraz S, Hurwitz HI, Pousa AL, Le Cesne A, Goldstein D, Paz-Ares L, Blay JY, McArthur GA, Xu QC, Huang X, Harmon CS, Tassell V, Cohen DP, Casali PG. Complete longitudinal analyses of the randomized, placebo-controlled, phase III trial of sunitinib in patients with gastrointestinal stromal tumor following imatinib failure. Clin Cancer Res. 2012 Jun 1;18(11):3170-9. link to original article link to PMC article PubMed
- AB07001: Adenis A, Blay JY, Bui-Nguyen B, Bouché O, Bertucci F, Isambert N, Bompas E, Chaigneau L, Domont J, Ray-Coquard I, Blésius A, Van Tine BA, Bulusu VR, Dubreuil P, Mansfield CD, Acin Y, Moussy A, Hermine O, Le Cesne A. Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial. Ann Oncol. 2014 Sep;25(9):1762-9. Epub 2014 Jul 25. link to original article link to PMC article PubMed NCT01506336
- AB11002: NCT01694277
Metastatic or unresectable disease, third-line
Most trials define this context as imatinib- and sunitinib-resistant.
Cabozantinib monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Schöffski et al. 2020 (CaboGIST) | 2017-2018 | Phase II |
Targeted therapy
- Cabozantinib (Cometriq) 60 mg PO once per day
28-day cycles
References
- CaboGIST: Schöffski P, Mir O, Kasper B, Papai Z, Blay JY, Italiano A, Benson C, Kopeckova K, Ali N, Dileo P, LeCesne A, Menge F, Cousin S, Wardelmann E, Wozniak A, Marreaud S, Litiere S, Zaffaroni F, Nzokirantevye A, Vanden Bempt I, Gelderblom H. Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 'CaboGIST'. Eur J Cancer. 2020 Jul;134:62-74. Epub 2020 May 26. link to original article contains protocol PubMed NCT02216578
Pazopanib monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mir et al. 2016 (PAZOGIST) | 2011-2013 | Randomized Phase II (E-esc) | Best supportive care | Seems to have superior PFS |
Targeted therapy
- Pazopanib (Votrient) 800 mg PO once per day
Continued indefinitely
References
- PAZOGIST: Mir O, Cropet C, Toulmonde M, Cesne AL, Molimard M, Bompas E, Cassier P, Ray-Coquard I, Rios M, Adenis A, Italiano A, Bouché O, Chauzit E, Duffaud F, Bertucci F, Isambert N, Gautier J, Blay JY, Pérol D; PAZOGIST study group of the French Sarcoma Groupe-Groupe d'Etude des Tumeurs Osseuses (GSF-GETO). Pazopanib plus best supportive care versus best supportive care alone in advanced gastrointestinal stromal tumours resistant to imatinib and sunitinib (PAZOGIST): a randomised, multicentre, open-label phase 2 trial. Lancet Oncol. 2016 May;17(5):632-41. Epub 2016 Apr 5. link to original article contains protocol PubMed NCT01323400
Regorafenib monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Demetri et al. 2012 (GRID) | 2011 | Phase III (E-RT-esc) | Placebo | Superior PFS Median PFS: 4.8 vs 0.9 mo (HR 0.27, 95% CI 0.19-0.39) |
Kang et al. 2021 (VOYAGER) | 2018-2019 | Phase III (C) | Avapritinib | Might have superior PFS Median PFS: 5.6 vs 4.2 mo (HR 0.80, 95% CI 0.64-1.01) |
Patients in GRID already had treatment failure with imatinib and sunitinib.
Targeted therapy
- 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. link to original article contains verified protocol link to PMC article PubMed NCT01271712
- VOYAGER: Kang YK, George S, Jones RL, Rutkowski P, Shen L, Mir O, Patel S, Zhou Y, von Mehren M, Hohenberger P, Villalobos V, Brahmi M, Tap WD, Trent J, Pantaleo MA, Schöffski P, He K, Hew P, Newberry K, Roche M, Heinrich MC, Bauer S. Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study. J Clin Oncol. 2021 Oct 1;39(28):3128-3139. Epub 2021 Aug 3. link to original article contains protocol link to PMC article PubMed NCT03465722
Sorafenib monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Kindler et al. 2011 | NR | Phase II |
Park et al. 2012 (SMC 2009-08-102) | 2009-2010 | Phase II |
Targeted therapy
- Sorafenib (Nexavar) 400 mg PO twice per day
Continued indefinitely
References
- Abstract: Kindler HL, Campbell NP, Wroblewski K, Maki RG, D’Adamo DR, Chow WA, Gandara DR, Antonescu C, Stadler WM, Vokes EE. Sorafenib (SOR) in patients (pts) with imatinib (IM) and sunitinib (SU)-resistant (RES) gastrointestinal stromal tumors (GIST): Final results of a University of Chicago Phase II Consortium trial. 2011. 29 (15_suppl) 10009-10009. link to original article (abstract only)
- SMC 2009-08-102: Park SH, Ryu MH, Ryoo BY, Im SA, Kwon HC, Lee SS, Park SR, Kang BY, Kang YK; Korean gastrointestinal stromal tumors study group. Sorafenib in patients with metastatic gastrointestinal stromal tumors who failed two or more prior tyrosine kinase inhibitors: a phase II study of Korean gastrointestinal stromal tumors study group. Invest New Drugs. 2012 Dec; 30(6) 2377-83. Epub 2012 Jan 25. link to original article contains protocol PubMed NCT01091207
Metastatic or unresectable disease, fourth-line
Many trials define this context as imatinib-, sunitinib-, and regorafenib-resistant.
Avapritinib monotherapy
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence |
---|---|---|
Heinrich et al. 2020 (NAVIGATOR) | 2015-2018 | Phase I (RT) |
Note: Patients in this study either had the PDGFRA D842V mutation or already had treatment failure with imatinib and ≥1 additional tyrosine kinase inhibitor. This is the recommended phase II dose.
Biomarker eligibility criteria
- Gene: PDGFRA
- Alteration: D842V
Chemotherapy
Avapritinib (Ayvakit) 300 mg PO once per day on an empty stomach (at least 1 hour before and 2 hours after a meal)
Continued indefinitely
References
- NAVIGATOR: Heinrich MC, Jones RL, von Mehren M, Schöffski P, Serrano C, Kang YK, Cassier PA, Mir O, Eskens F, Tap WD, Rutkowski P, Chawla SP, Trent J, Tugnait M, Evans EK, Lauz T, Zhou T, Roche M, Wolf BB, Bauer S, George S. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020 Jul;21(7):935-946. Erratum in: Lancet Oncol. 2020 Sep;21(9):e418. link to original article contains protocol PubMed NCT02508532
Ripretinib monotherapy
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Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Blay et al. 2020 (INVICTUS) | 2018 | Phase III (E-RT-esc) | Placebo | Superior PFS |
Targeted therapy
- Ripretinib (Qinlock) 150 mg PO once per day
Continued indefinitely
References
- INVICTUS: Blay JY, Serrano C, Heinrich MC, Zalcberg J, Bauer S, Gelderblom H, Schöffski P, Jones RL, Attia S, D'Amato G, Chi P, Reichardt P, Meade J, Shi K, Ruiz-Soto R, George S, von Mehren M. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jul;21(7):923-934. Epub 2020 Jun 5. Erratum in: Lancet Oncol. 2020 Jul;21(7):e341. link to original article contains protocol PubMed NCT03353753