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VP3-2024: A randomized study of 6 vs 3 years of adjuvant imatinib in patients with localized GIST at high risk of relapse
Published: May 9, 2024
DOI: https://doi.org/10.1016/j.annonc.2024.04.004
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A. Le Cesne, C. Schiffler, O. Bouche, ..., J-Y. Blay
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Background
Adjuvant imatinib is indicated after complete resection of primary localized GIST at high risk of recurrence. Many of these patients relapse after the end of 3 year adjuvant imatinib. Whether prolonging adjuvant imatinib beyond 3 years may reduce GIST recurrence has not been explored in a randomized setting.
Methods
IMADGIST (NCT02260505) is a multicenter open-label, randomized, phase III study evaluating the maintenance of imatinib for 3 more years (6-Years arm) at the last dose taken prior to randomization (either 300 or 400 mg/d), compared to Interruption of imatinib treatment (3-Years arm) from the day of randomization. The primary endpoint is intent-to treat disease-free survival (DFS). Secondary endpoints include overall survival, time to imatinib resistance, response and progression free survival (PFS) after imatinib reintroduction at relapse, safety. A sample size of 134 patients was calculated to detect an improvement of 15% in 3-year DFS rate (75% vs. 90% in the 3-Years and 6-Years arms, respectively). Data cut-off was set to September 30th, 2023.
Results
From December 24th, 2014 to April 4th, 2023; 136 patients aged ≥18, ECOG PS ≤2, with confirmed diagnosis of localized GIST with KIT expression, a R0 or R1 surgery, and a risk of tumor recurrence ≥35% according to National Comprehensive Cancer Network Task Force on GIST (NCCN) risk classification were randomized in 14 French cancer centers. Sixty-five patients were randomized to the 3-Years arm vs. 71 in the 6-Years arm. There were 68 males and females. Primary site were gastric and small bowel in 60 (44.1%) and 64 (47.1%) patients respectively. 68 (50%) had tumor size>10cm, 94 (69.1%) a mitotic index>5/50 HPF. 19 (13.9%) had tumor rupture, 52 (38.2%) and 71 (52.2%) patients had a risk of relapse of 35-70% and >70%. With a median follow-up of 58 months post randomization, disease free survival was significantly superior in the group receiving 6-Years arm (HR: 0.40 [0.20-0.69], p=0.0008). Time to imatinib resistance, overall survival, adverse events are not significantly different in the 2 arms with the present follow-up.
Conclusions
Three additional years of adjuvant imatinib improves DFS in patients who already received 3 years of adjuvant imatinib with an acceptable tolerance.
Clinical trial identification
NCT02260505.
Legal entity responsible for the study: Centre Léon Bérard.
Funding: Programme Hospitalier de Recherche Clinique.
Disclosure: A. Le Cesne: Financial Interests, Personal, Research Grant: Novartis.
M. Brahmi: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Amgen, PharmaMar, Deciphera.
I. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Eisai, Sutro, BMS, Daiichi Sankyo, ImmunoGen, Seagen, PMV Pharma; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Personal, Principal Investigator: PAOLA1; Non-financial Interests, Personal, Other, President: GINECO.
J-Y. Blay: Financial Interests, Institutional, Invited Speaker: MSD, PharmaMar; Financial Interests, Institutional, Advisory Board: Bayer, GSK, Roche; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Personal, Other, member of the supervisory board, no remunerations in 2021 and 2022: Innate Pharma; Financial Interests, Personal, Member of Board of Directors: Transgene; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bayer, GSK, Novartis, OSE Pharma.
All other authors have declared no conflicts of interest.
