Comparative evaluation of capecitabine or infusional leucovorin/5-fluorouracil (LV/5-FU) with or without oxaliplatin (Ox) for stage III colon cancer (CC): A pooled analysis of individual patient data from four randomized controlled trials.
3525 Background: A fluoropyrimidine + Ox is the standard of care for stage III CC but a fluoropyrimidine alone is recommended for selected patients in several practice guidelines. We assessed efficacy and safety of adjuvant capecitabine ± Ox vs. LV/5-FU ± Ox across a population of stage III CC patients enrolled in four trials. Methods: N = 5,819 patients from NSABP C-08, XELOXA, X-ACT, and AVANT were pooled and analyzed; bevacizumab-treated patients were excluded. Endpoints were disease-free survival (DFS, primary), relapse-free survival (RFS), overall survival (OS), and safety. Multivariate Cox regression analyses (MVA) controlled for age, gender, T, and N stage. Results: Patient demographics and disease characteristics (except lymph nodes examined) were well balanced across groups. The number of patients receiving capecitabine and LV/5-FU were 1,942 and 3,877, respectively. Median follow-up was shorter in NSABP C-08 and AVANT (36 and 50 months) vs. XELOXA and X-ACT (83 and 74 months). Five-year DFS was 62.8% for capecitabine ± Ox and LV/5-FU ± Ox. The capecitabine by Ox interaction was significant for OS with a trend for DFS and RFS; likely due to improved outcomes with capecitabine alone and similar outcomes for capecitabine or LV/5-FU + Ox. Serious adverse event (AE) rates were similar for LV/5-FU- and capecitabine-based therapy (16% vs. 20%, respectively). Overall, treatment-related grade 3/4 AEs were more common with LV/5-FU (59% vs. 47%). Treatment-related grade 3/4 AEs of interest included peripheral sensory neuropathy (5% vs. < 1%), diarrhea (12% vs. 15%), febrile neutropenia (2% vs. < 1%), and hand–foot syndrome (< 1% vs. 12%). Conclusions: Adjuvant capecitabine ± Ox and LV/5-FU ± Ox show comparableefficacy benefits for the treatment of stage III CC; further supporting capecitabine or LV/5-FU-based regimens as standard options for the adjuvant therapy of stage III CC. [Table: see text]