Gender and survival benefit from initial irinotecan in metastatic colorectal cancer: Analysis of the XELAVIRI (AIOKRK0110) study.

Abstract

3559 Background: XELAVIRI compared initial vs sequential irinotecan (iri) in combination with fluoropyrimidine (FP) plus bevacizumab (bev) in patients (pts) with mCRC, trial identification: NCT01249638. In the full analysis set of the study, non-inferiority of time to failure of strategy (TFS) was not shown (primary endpoint). Pts with RAS/BRAF wildtype (wt) tumors benefitted from initial iri. Methods: The study endpoints objective response rate (ORR), progression-free survival (PFS), time to failure of strategy (TFS) as well as overall survival (OS) were evaluated in female vs. male pts as well as molecular subgroups (i.e. RAS mutational status). Interaction of treatment and gender was tested by likelihood ratio tests. Results: Of 421 patients, 281/140 were male/female. In male patients, ORR was 33.6% without and 58.3% with initial iri (P < 0.001). PFS (HR: 0.54 (95%CI 0.42-0.69) P < 0.001) and OS (HR: 0.63 (95%CI 0.47-0.85), P = 0.002), were also significantly better with initial iri. In the subgroup analysis, this effect was especially pronounced in pts with RAS/BRAF wt tumors. In female pts, ORR was 43% in both arms, PFS was similar (HR: 1.09 (95%CI 0.76-1.55), P = 0.65) without and with initial iri. In OS, a strong trend for inferior outcome with initial iri was seen (HR: 1.46 (95%CI 0.95-2.24), P = 0.08) that reached significance in the multivariate analysis (HR: 1.73 (95%CI 1.04-2.86, P = 0.034). Female patients with RAS/BRAF wt tumors did not benefit from initial iri (HR 1.05 (95% CI 0.46-2.41), P = 0.903 for OS). Formal interaction of treatment and gender was seen for ORR (P = 0.018), PFS (P = 0.002) and OS (P = 0.001). There were some trends for more pronounced toxicities in female pts treated with Irinotecan. Conclusions: This unplanned exploratory analysis suggests that gender might interact with efficacy of initial iri when used in the context of FP and bev. While especially male RAS wild-type patients derived a significant and clinically meaningful benefit from initial use of iri, this was not observed in female patients with RAS wt tumors. Clinical trial information: NCT01249638.