As reported in the Journal of Clinical Oncology by Conca et al, the final results of the Italian phase III TRIPLETE trial showed that first-line mFOLFOXIRI (modified fluorouracil, leucovorin, oxaliplatin, irinotecan) plus panitumumab improved overall survival vs mFOLFOX (modified fluorouracil, leucovorin, oxaliplatin) plus panitumumab in patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC).
Study Details
In the multicenter open-label trial, 435 patients were randomly assigned to receive either mFOLFOXIRI/panitumumab (n = 218) or mFOLFOX/panitumumab (n = 217). The primary analysis from the trial showed no significant difference between groups in objective response rate (primary endpoint), with no difference in progression-free survival being observed.
Key Findings
Median follow-up for the current analysis was 60.2 months (interquartile range = 49.3–70.0 months).
Median overall survival was 41.1 months (95% confidence interval [CI] = 33.7–50.1 months) in the mFOLFOXIRI/panitumumab group vs 33.3 months (95% CI = 28.6–36.8 months) in the mFOLFOX/panitumumab group (hazard ratio [HR] = 0.79, 95% CI = 0.63–0.99, P = .049). Hazard ratios for overall survival favored mFOLFOXIRI/panitumumab, irrespective of clinical features.
An absence of significant differences between the mFOLFOXIRI/panitumumab group vs the mFOLFOX/panitumumab group was confirmed for objective response rate (78% vs 75%, odds ratio = 0.84, P = .442), early tumor shrinkage rate (P = .954), depth of response (P = .573), no residual tumor resection rate (P = .329), and progression-free survival (HR = 0.95, 95% CI = 0.78–1.16, P = .606).
Among patients alive at the time of disease progression, the median postprogression survival was 24.6 months in the mFOLFOXIRI/panitumumab group vs 17.7 months in the mFOLFOX/panitumumab group (HR = 0.79, 95% CI = 0.62–1.01, P = .062). Receipt of subsequent treatment in the two groups was similar, including second-line in 73% vs 71% of patients, third-line in 51% vs 49%, and fourth-line in 31% vs 32%; receipt of nonpalliative locoregional treatment was also similar (16% vs 16%).
The investigators concluded: “Upfront mFOLFOXIRI/panitumumab significantly improves [overall survival] compared with mFOLFOX/panitumumab in patients with RAS/BRAF wild-type mCRC.”
Chiara Cremolini, MD, PhD, of Azienda Ospedaliero–Universitaria Pisana, Pisa, Italy, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the GONO Foundation, Amgen, and others. For full disclosures of the study authors, visit ascopubs.org.
