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Randomized Controlled Trial
. 2021 Apr;32(4):533-541.
doi: 10.1016/j.annonc.2021.01.004. Epub 2021 Jan 19.

Final analysis of the randomized trial on imatinib as an adjuvant in localized gastrointestinal stromal tumors (GIST) from the EORTC Soft Tissue and Bone Sarcoma Group (STBSG), the Australasian Gastro-Intestinal Trials Group (AGITG), UNICANCER, French Sarcoma Group (FSG), Italian Sarcoma Group (ISG), and Spanish Group for Research on Sarcomas (GEIS)☆

P G Casali  1 , A Le Cesne  2 , A P Velasco  3 , D Kotasek  4 , P Rutkowski  5 , P Hohenberger  6 , E Fumagalli  7 , I R Judson  8 , A Italiano  8 , H Gelderblom  9 , N Penel  10 , J T Hartmann  11 , F Duffaud  12 , D Goldstein  13 , J Martin-Broto  14 , A Gronchi  15 , E Wardelmann  16 , S Marréaud  17 , J R Zalcberg  18 , S Litière  17 , J-Y Blay  19
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Free article
Randomized Controlled Trial

Final analysis of the randomized trial on imatinib as an adjuvant in localized gastrointestinal stromal tumors (GIST) from the EORTC Soft Tissue and Bone Sarcoma Group (STBSG), the Australasian Gastro-Intestinal Trials Group (AGITG), UNICANCER, French Sarcoma Group (FSG), Italian Sarcoma Group (ISG), and Spanish Group for Research on Sarcomas (GEIS)☆

P G Casali et al. Ann Oncol. 2021 Apr.
Free article

Abstract

Background: In 2004, we started an intergroup randomized trial of adjuvant imatinib versus no further therapy after R0-R1 surgery in localized, high/intermediate-risk gastrointestinal stromal tumors (GIST) patients. Interim analysis results were published in 2015 upon recommendation from an independent data review committee. We report the final outcome of the study.

Patients and methods: This was a randomized, open-label, multicenter phase III trial carried out at 112 hospitals in 12 countries. Patients were randomized to 2 years of imatinib, 400 mg daily, or no further therapy after surgery. The primary endpoint was imatinib failure-free survival (IFFS), while relapse-free survival (RFS), relapse-free interval (RFI), overall survival (OS) and toxicity were secondary endpoints. Adjusting for the interim analyses, results on IFFS were assessed on a 4.3% significance level; for the other endpoints, 5% was used.

Results: Nine hundred and eight patients were randomized between January 2005 and October 2008: 454 to imatinib and 454 to observation; 835 patients were eligible. With a median follow-up of 9.1 years, 5 (10)-year IFFS was 87% (75%) in the imatinib arm versus 83% (74%) in the control arm [hazard ratio (HR) = 0.87, 95.7% confidence interval (CI) (0.65; 1.15), P = 0.31]; RFS was 70% versus 63% at 5 years and 63% versus 61% at 10 years, [HR = 0.71, 95% CI (0.57; 0.89), P = 0.002]; OS was 93% versus 92% at 5 years and 80% versus 78% at 10 years [HR = 0.88, 95% CI (0.65; 1.21), P = 0.43]. Among 526 patients with high-risk GIST by local pathology, 10-year IFFS and RFS were 69% versus 61%, and 48% versus 43%, respectively.

Conclusions: With 9.1 years of follow-up, a trend toward better long-term IFFS in imatinib-treated patients was observed in the high-risk subgroup. Although the difference was not statistically significant and the surrogacy value of such an endpoint is not validated, this may be seen as supporting the results reported by the Scandinavian/German trial, showing a sustained small but significant long-term OS benefit in high-risk GIST patients treated with 3 years of adjuvant imatinib.

Keywords: adjuvant; gastrointestinal stromal tumors (GIST); imatinib.

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Conflict of interest statement

Disclosure In the last 3 years, PGC had honoraria for speaker, consultancy or advisory role from Bayer, Deciphera, Eisai, Eli Lilly, Pfizer. At PC's institution, PC Unit received funds from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc., Glaxo, Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar. At EF's institution, PC Unit received funds from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc., Glaxo, Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar. IRJ had honoraria from the Institute of Cancer Research. AI had honoraria from Epizyme, Bayer, Lilly, Roche, SpringWorks Therapeutics and non-financial support from Epizyme, Merck; AI's institution had research grants from AstraZeneca, Bayer, Chugai, MSD, BMS, Novartis, Roche. ALC had honoraria from PharmaMar, Deciphera, Lilly, Bayer. PR received honoraria from Novartis, Pfizer, MSD, BMS, Merck, Pierre Fabre, Roche, Sanofi for lectures and advisory boards. FD had honoraria from Bayer, Leo Pharma, PharmaMar, Lilly and funding for travel/for meetings from PharmaMar, Leo Pharma. DG: advisory role for Deciphera. JMB had honoraria for advisory board participation and expert testimony from PharmaMar, Eli Lilly and Company, Bayer and Eisai, and research grants from PharmaMar, Eisai, Immix Biopharma and Novartis. At JMB's institution, grants were received from PharmaMar, Eli Lilly and Company, Adaptimmune Therapeutics, AROG, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Novartis, Blueprint, Nektar, Forma, Amgen and Daiichi Sankyo. EW received honoraria, research and travel grants from Nanobiotix, Milestone/Menarini, New Oncology, Lilly, Novartis Oncology, Roche and Bayer. J-YB had honoraria and research support from Novartis, Bayer and Deciphera. All other authors have declared no conflicts of interest.

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