Cetuximab Combination Improves PFS in Metastatic Colorectal Cancer

Modified FOLFOXIRI plus cetuximab improved progression-free survival compared with modified FOLFOXIRI plus bevacizumab in patients with left-sided, RAS/BRAF wild-type metastatic colorectal cancer, according to the final analysis of the randomized phase 2 DEEPER trial published in the Journal of Clinical Oncology.

The multicenter trial enrolled 359 patients with RAS wild-type metastatic colorectal cancer. The updated exploratory analysis included 178 patients with left-sided, RAS/BRAF wild-type tumors: 86 assigned to cetuximab and 92 assigned to bevacizumab, each combined with modified 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan.

Median progression-free survival was 14.8 months with cetuximab and 11.9 months with bevacizumab (hazard ratio [HR], 0.71; 95% CI, 0.52-0.97; P=0.029). Median overall survival was 50.2 months and 40.2 months, respectively (HR, 0.74; 95% CI, 0.53-1.05; P=0.091).

Exploratory analyses suggested longer overall survival with cetuximab among male patients and those with extrahepatic disease. Grade 3 or 4 adverse-event rates were comparable between groups, and investigators reported no new safety signals.

The phase 2 study was not powered to establish an overall-survival benefit. Subgroup analyses were exploratory and were not adjusted for multiple comparisons, BRAF status was unavailable for some patients at enrollment, and subsequent therapies may have affected survival.

Source: Sunakawa Y, Shiozawa M, Watanabe T, et al. Long-term survival outcomes of modified-FOLFOXIRI plus cetuximab versus bevacizumab in RAS/BRAF wild-type metastatic colorectal cancer: final analysis of the DEEPER trial. J Clin Oncol. Published online August 27, 2026. doi:10.1200/JCO-26-00355