Efficacy and safety of a cetuximab biosimilar compared with Erbitux in patients with RAS wild-type metastatic colorectal cancer

Cetuximab, an epidermal growth factor receptor monoclonal antibody, is a key therapy for RAS wild-type metastatic colorectal cancer (mCRC), commonly used with folinic acid, 5-fluorouracil, and irinotecan (FOLFIRI). In Iran, the rising burden of mCRC and the high cost of imported cetuximab underscore the urgent need for a cost-effective, locally manufactured biosimilar to improve treatment accessibility and sustainability within the healthcare system. The objective of this study is to compare the efficacy, safety, and immunogenicity of cetuximab (manufactured by CinnaGen Co.) versus reference cetuximab (Erbitux; manufactured by Merck) in patients with RAS wild-type mCRC. This phase III, double-blind, randomized, multi-center, active-controlled trial enrolled adult patients (n = 211) with RAS wild-type mCRC. Participants were allocated 2:1 to cetuximab (CinnaGen) plus FOLFIRI (n = 141) or Erbitux plus FOLFIRI (n = 70) for up to 48 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), time to treatment failure (TTF), objective response rate (ORR), safety, and immunogenicity. The results show that cetuximab (CinnaGen) was comparable to Erbitux for PFS in both PP (hazard ratio [HR] = 0.95; 90% confidence interval [CI]: 0.62–1.45) and ITT (HR = 0.82; 90% CI: 0.55–1.24) analyses, with upper CIs below the non-inferiority margin (1.51). No significant differences were observed in OS (HR = 0.85; 95% CI: 0.45–1.58), TTF (HR = 1.07; 95% CI: 0.77–1.48), or ORR (43.3% vs 45.7%; P-value = 0.77). The majority of patients experienced adverse events, with anemia, neutropenia, and hypomagnesemia being among the most frequently reported. The frequency of serious adverse events was considered clinically acceptable, and immunogenicity analyses revealed no detectable anti-cetuximab antibodies in either treatment group. In conclusion, this study demonstrated that cetuximab (CinnaGen) is non-inferior to Erbitux (Merck) in terms of PFS, with comparable efficacy across other endpoints. The safety profiles of both products were acceptable and consistent with known data for cetuximab-based regimens in mCRC.