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Three versus six months’ adjuvant oxaliplatin-based chemotherapy for patients with stage III colon cancer: Per-protocol, subgroups and long-lasting neuropathy results

2017; Elsevier BV; Volume: 28; Linguagem: Inglês

10.1093/annonc/mdx393

1569-8041

Julien Taı̈eb, Franck Bonnetain, Laurent Mineur, Jaafar Bennouna, Jérôme Desramé, Roger Faroux, Serge Fratté, Jérôme Dauba, Déwi Vernerey, Christophe Louvet, Céline Lepère, Olivier Dupuis, Y. Bécouarn, May Mabro, Joëlle Egreteau, Olivier Bouché, G. Deplanque, Marc Ychou, Aimery de Gramont, Thierry André,

Colorectal Cancer Surgical Treatments

Background: The International Duration Evaluation of Adjuvant chemotherapy (IDEA) collaboration was established to combine data from 6 randomized trials to assess whether 3-month (3M) of oxaliplatin/fluoropyrimidines-based adjuvant chemotherapy is non-inferior to 6-month (6M) for 3-year disease-free survival (DFS) in stage III colon cancer (CC). Methods: IDEA France randomized patients (pts) between 3M and 6M of chemotherapy with mFOLFOX6 or XELOX (physician choice). DFS was estimated using the Kaplan–Meier method and described using a 3-year DFS rate with 95% confidence interval (CI). Cox-proportional-hazard models were performed to estimate the hazard ratios (HRs) and 95% CIs. We present here the results in the modified ITT (mITT: pts receiving at least one dose of treatment) and modified per-protocol (mPP: pts receiving 3M in the 3M arm and >5M in the 6M arm) populations. Subgroups and long lasting neuropathy results are also reported here. Results: From May 2009 to May 2014, 2022 pts were randomized from 129 centers and 2010 (99%) and 1757 (87%) were included in the mITT and mPP populations, respectively. With a median follow-up of 4.3 years, the 3-year DFS rate was 72% and 76% (HR = 1.24; 95% CI 1.05–1.46, p = 0.01) for the 3M and 6M mITT populations, respectively and 72% and 78% (HR = 1.36; 95% CI 1.14–1.63, p = 0.0008) for the 3M and 6 M mPP populations. In the mITT FOLFOX treated population (90% of pts), 3-year DFS was 81% (3M) and 83% (6M) for T1-3/N1 pts (N = 1106, HR = 1.15 95%CI 0.89-1.49) and 58% (3M) and 66% (6M) for T4/N2 pts (N = 702, HR = 1.44 95%CI 1.14-1.82). Grade >1 neuropathy was observed in 36% and 67% of pts (p < 0.0001) in the 3M and 6M arms, respectively. With a median follow-up of 3.6 years, final residual grade >1 neuropathy was 2.8% and 7.4% (p < 0.0001), in the 3M and 6M arms, respectively. Conclusions: The IDEA France study, with 90% of pts treated with mFOLFOX6, shows that 6M adjuvant treatment is superior to 3M. However, this difference was not significant in the mITT and mPP T1-3N1 populations suggesting that 3M of the mFOLFOX6 regimen could be an option for these pts. Clinically relevant (grade>1) neuropathy was significantly higher in the 6M arm, with long-lasting neuropathy in 7.4% of pts. Clinical trial identification: Registration Number (European Union Drug Regulating Authorities Clinical Trials): 2009-010384-16 Legal entity responsible for the study: GERCOR - Groupe Coopérateur Multidisciplinaire en Oncologie Funding: French Ministry of Health and French National Cancer Institute (INCa) Disclosure: J. Taieb: Advisory board or Board of directors: Sanofi, Baxalta, Roche, Merck, Amgen, Lilly, Celgene. F. Bonnetain: Advisory board or Board of directors: Roche, Ipsen, Amgen, Nestle, Novartis; corporate-sponsored research: Novartis, Roche. L. Mineur: Advisory board or Board of directors: Amgen, Sanofi, Bayer, Roche; corporate-sponsored research: Sanofi, Merck, Chugai. J. Bennouna: Advisory board or Board of directors and honorarium: BMS, Roche, Boehringer Ingelheim, AstraZeneca. D. Vernerey: Honorarium: Janssen, Celgene. Advisory board: HallioDx. C. Lepere: Advisory board or Board of directors: Ipsen. O. Bouche: Advisory board or Board of directors: Merck Serono, Roche, Amgen. M. Ychou: Advisory board or Board of directors: Roche, Bayer, Amgen, Lilly. T. André: Advisory board or Board of directors: BMS, Amgen, Roche; corporate-sponsored research: BMS, Roche; honoraria: Baxter, Bayer, Lilly, MSD, Sanofi, Mundipharma, Novartis. All other authors have declared no conflicts of interest.