Extended RAS Analysis of the Phase 3 EPIC Trial: Irinotecan + Cetuximab vs Irinotecan as Second‐Line Treatment for Patients with Metastatic Colorectal Cancer

BACKGROUND The multicenter, open-label, randomized, phase 3 EPIC study (EMR 062202-025) investigated cetuximab plus irinotecan vs irinotecan in patients with epidermal growth factor receptor-detectable metastatic colorectal cancer (mCRC) that progressed on first-line fluoropyrimidine- and oxaliplatin-based chemotherapy; we report the outcomes of patients with RAS-wild-type (wt) disease. MATERIALS AND METHODS Available DNA samples from RAS-unselected patients (n = 1164 of 1298 [89.7%]) were reanalyzed for RAS mutations using BEAMing. Baseline characteristics, efficacy, safety, and post-study therapy were assessed. RAS-wt status was defined as a mutated RAS allele frequency of ≤5%, with all relevant alleles being analyzable. RESULTS Baseline characteristics were comparable between the groups (N = 452 patients with RAS-wt mCRC; cetuximab plus irinotecan n = 231, irinotecan n = 221) and between the RAS-wt and RAS-unselected populations. In the cetuximab plus irinotecan vs irinotecan arms, median overall survival was 12.3 vs 12.0 months, median progression-free survival (PFS) was 5.4 vs 2.6 months, and objective response rate (ORR) was 29.4% vs 5.0%, respectively. Quality of life (QoL) was improved in the cetuximab plus irinotecan arm. Serious adverse events occurred in 45.4% (cetuximab plus irinotecan) and 42.4% (irinotecan) of patients. In total, 47.1% of patients in the irinotecan arm received subsequent cetuximab therapy. CONCLUSION PFS, ORR, and QoL were improved with cetuximab plus irinotecan as a second-line treatment in patients with RAS-wt mCRC, confirming that cetuximab-based therapy is suitable in this population. Almost half of patients in the irinotecan arm received post-study cetuximab, masking a potential OS benefit of cetuximab addition. IMPLICATIONS FOR PRACTICE Cetuximab is approved for the treatment of RAS-wild-type metastatic colorectal cancer (mCRC). In this retrospective analysis of the phase 3 EPIC study (cetuximab plus irinotecan versus irinotecan alone as second-line treatment in patients with RAS-unselected mCRC), the subgroup of patients with RAS-wild-type mCRC who received cetuximab plus irinotecan had improved progression-free survival, objective response rate, and quality of life compared with the RAS-unselected population. These findings suggest that cetuximab-based therapy is a suitable second-line treatment for patients with RAS-wild-type mCRC.