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

Abstract

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 6MmPP 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 6Marms, 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 6Marms, 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.