Since 2004, 6 months (m) of oxaliplatin (oxali)-based treatment has been the standard of care as adjuv therapy for stage III CC. As oxali is associated with cumulative neurotoxicity, a shorter duration of adjuv therapy could spare pts toxicity and lead to substantial saving in health expenditures.
A prospective, pre-planned pooled analysis of 6 concurrently conducted randomized phase 3 trials (SCOT, TOSCA, Alliance/SWOG 80702, IDEA France, ACHIEVE, HORG) was performed to evaluate the non-inferiority (NI) of 3m compared with 6m (ref) of adj FOLFOX/CAPOX. The primary endpoint was disease-free survival (DFS), defined as time from enrolment to relapse, 2nd CRC, and death (all causes). NI was to be declared if the 2-sided 95% confidence interval (CI) for DFS Hazard Ratio (HR 3m v 6m) estimated by a stratified Cox model was below 1.12. NI was examined within regimen and stage subgroups as pre-planned.
The analysis included 12,834 pts from 12 countries, accrued 6/07-12/15. After 3263 (of 3390 expected) DFS events NI for the shorter duration of therapy could not be confirmed for the overall study population (HR 1.07, 95%CI 1.00-1.15). NI of 3m v 6m was seen for CAPOX (HR 0.95, 95%CI 0.85-1.06; whereas 3m of FOLFOX was inferior to 6m (HR 1.16, 95%CI 1.06-1.26). Pts treated with CAPOX (vs FOLFOX) had a higher rate of T4 CC (24.3% vs 18.6%, p
The IDEA results provide the basis for individual adjustments of adj treatment duration based on risk of recurrence, pt preference, toxicity and the chemotherapy regimen used. Further analyses are warranted to explain the different performance of CAPOX and FOLFOX with regard to the NI question.
Clinical trial identification
NCT00749450 (SCOT); NCT00646607 (TOSCA); NCT01150045 (CALGB/SWOG 80702); NCT00958737 (IDEA France); NCT01308086 (HORG); UMIN-CTR Clinical Trial Identifier: UMIN000008543 (ACHIEVE)
Legal entity responsible for the study
Mayo Clinic, U10CA180821, U10CA180835, U10CA180882, U10CA180888, U10CA180835, INCA, PHRC2009, EME 09/800/34, HTA 14/140/84, CRUK C1348/A15960, JFMC
All authors have declared no conflicts of interest.