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Background: The multicenter, open‐label, randomized, phase III EPIC study (EMR 062202‐025) investigated cetuximab plus irinotecan versus 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 = 1,164 of 1,298 [89.7%]) were reanalyzed for RAS mutations using beads, emulsion, amplification, and magnetics. Baseline characteristics, efficacy, safety, and poststudy 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 versus irinotecan arms, median overall survival was 12.3 versus 12.0 months, median progression‐free survival (PFS) was 5.4 versus 2.6 months, and objective response rate (ORR) was 29.4% versus 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 poststudy cetuximab, masking a potential overall survival 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 III EPIC study (cetuximab plus irinotecan vs. 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. This article analyzes outcomes of patients with RAS‐wild‐type metastatic colorectal cancer who received cetuximab plus irinotecan versus irinotecan alone in the EPIC trial. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and safety of cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer (mCRC) patients from South-East Asia and Australia., Methods: In this open-label, phase II study, the main eligibility criteria were epidermal growth factor receptor-positive mCRC with progressive disease within 3 mo of an irinotecan-based regimen as the most recent chemotherapy. Patients received cetuximab 400 mg/m2 initially, then 250 mg/m2 every week, with the same regimen of irinotecan on which the patients had progressed (4 pre-defined regimens allowed). The primary objective was evaluation of progression-free survival (PFS) at 12 wk. Secondary objectives included a further investigation of PFS, and an assessment of the overall response rate (ORR), duration of response, time to treatment failure (TTF), overall survival and the safety profile., Results: One hundred and twenty nine patients were enrolled from 25 centers in the Asia-Pacific region and of these 123 received cetuximab plus irinotecan. The most common recent irinotecan regimen used was 180 mg/m2 every 2 wk which had been used in 93 patients (75.6%). The PFS rate at 12 wk was 50% (95% confidence interval (CI, 41-59) and median PFS time was 12.1 wk (95% CI: 9.7-17.7). The ORR was 13.8% (95% CI: 8.3-21.2) and disease control rate was 49.6% (95% CI: 40.5-58.8). Median duration of response was 31.1 wk (95% CI: 18.0-42.6) and median overall survival was 9.5 mo (95% CI, 7.5-11.7). The median TTF was 11.7 wk (95% CI: 9.1-17.4). Treatment was generally well tolerated. The most common grade 3/4 adverse events were diarrhea (13.8%), neutropenia (8.9%), rash (5.7%) and vomiting (5.7%)., Conclusion: In patients from Asia and Australia, this study confirms the activity and safety of cetuximab plus irinotecan observed in previous studies in Europe and South America.

Aim: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC)., Methods: Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117)., Results: No significant difference was found between treatment arms A and B in the progression-free survival (PFS) rate at 9 mo, 45% vs 34%; median PFS, 8.6 mo vs 8.3 mo [hazard ratio (HR) = 1.06]; overall response rate (ORR) 43% vs 45% [odds ratio (OR) = 0.93] and median overall survival (OS), 17.4 mo vs 18.9 mo (HR = 0.98). Patients with KRAS wild-type tumors demonstrated improved PFS (HR = 0.55, P = 0.0051), OS, (HR = 0.62, P = 0.0296) and ORR (53% vs 36%) and in arm A, improved PFS (HR = 0.49, P = 0.0196), OS (HR = 0.48, P = 0.0201) and ORR (56% vs 30%), compared with patients with KRAS mutated tumors. In arm B no significant differences were found in efficacy by KRAS mutation status. Treatment in arms A and B was generally well tolerated., Conclusion: This study confirms that combinations of cetuximab with FOLFOX6 or FOLFIRI are effective and significantly improve clinical outcome in KRAS wild-type compared with KRAS mutated mCRC.