Upfront Modified FOLFOXIRI Plus Panitumumab for <i>RAS/BRAF</i> Wild-Type Metastatic Colorectal Cancer: Final Results of the Phase III TRIPLETE Study.

Abstract

We report 5-year results of the phase III randomized TRIPLETE study. Eligible patients with <i>RAS/BRAF</i> wild-type metastatic colorectal cancer (mCRC) received first-line modified fluorouracil, leucovorin, oxaliplatin (mFOLFOX)/panitumumab (control group, n = 217) versus modified fluorouracil, leucovorin, oxaliplatin, irinotecan (mFOLFOXIRI)/panitumumab (experimental group, n = 218). We present overall survival (OS) and updated outcomes in the intention-to-treat population. The median follow-up was 60.2 months (IQR, 49.3-70.0). The median OS was 41.1 and 33.3 months for experimental and control groups, respectively (hazard ratio [HR], 0.79 [95% CI, 0.63 to 0.99]; <i>P</i> = .049). OS outcomes favored the experimental group regardless of clinical features. No differences in objective response rate (primary end point; 75%/78%, odds ratio, 0.84 [95% CI, 0.54 to 1.31]; <i>P</i> = .442), early tumor shrinkage rate (<i>P</i> = .954), depth of response (<i>P</i> = .573), no residual tumor resection rate (<i>P</i> = .329), and progression-free survival (HR, 0.95 [95% CI, 0.78 to 1.16]; <i>P</i> = .606) were confirmed. Among patients alive at the time of disease progression, the median postprogression survival was 24.6 and 17.7 months for experimental and control groups, respectively (HR, 0.79 [95% CI, 0.62 to 1.01]; <i>P</i> = .062). Similar proportions of patients in both groups received subsequent lines of therapy (control/experimental: second line 73%/71%, third line 51%/49%, fourth line 31%/32%), as well as nonpalliative locoregional treatments (control/experimental: 16%/16%). Upfront mFOLFOXIRI/panitumumab significantly improves OS compared with mFOLFOX/panitumumab in patients with <i>RAS/BRAF</i> wild-type mCRC.