Concomitant proton pump inhibitors and capecitabine-based chemoradiotherapy in rectal cancer: an ancillary study from the PRODIGE 23 trial

Background: Approximately one in five cancer patients use proton pump inhibitors (PPIs). In this work, we studied the effect of PPI co-medication during neoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer (LARC) based on the phase III PRODIGE 23 trial. Materials and methods: We gathered data on PPI exposure for patients from the PRODIGE 23 trial. PPI exposure was defined as PPI use during capecitabine treatment, either during CRT or as adjuvant therapy. The oncological outcomes included recurrence-free survival (RFS), overall survival (OS), cumulative incidence of metastatic recurrence, and pathological response to preoperative treatment. The association of PPI use with RFS, metastatic recurrence, and histological complete response was evaluated using univariate and multivariate Cox models. Results: We analyzed data from 332 patients [165 in the NAC group with mFOLFIRINOX, capecitabine-based (CAP50) CRT, and surgery, and 167 in the standard-of-care control arm with CAP50 CRT and surgery]. Thirty-eight patients were co-administered a PPI during capecitabine administration. After a median follow-up of 49.4 months, the 3-year RFS rates were 74.1% [95% confidence interval (CI) 68.6% to 78.8%] and 68.4% (95% CI 51.2% to 80.7%) in the non-PPI and PPI groups, respectively, with no significant differences (P = 0.16). The 3-year OS rates were 91.2% (95% CI 87.2% to 93.9%) and 83% (95% CI 65.7% to 92%) in the non-PPI group and PPI groups, respectively, with no significant differences (P = 0.38). We observed no difference in the pathological complete response rate between both groups. Conclusions: We observed no significant association between PPI exposure and survival or pathological response of patients receiving capecitabine-based CRT for LARC, supporting earlier research findings.