A multicenter randomized phase II trial assessing the efficacy and safety of mCapOX plus cetuximab with mFOLFOX6 plus cetuximab as first-line treatment for RAS/BRAF wild-type metastatic colorectal cancer: Updated results from the CAPCET study.

3598 Background: The CAPCET study was designed to assess the efficacy and safety of modified capecitabine and oxaliplatin (mCapOX) plus cetuximab (CET) and modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus cetuximab (CET) for the first-line treatment of left-side unresectable RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC). Methods: CAPCET was an open-label, randomized, multicenter, phase II non-comparative trial (NCT05022030). Patients with unresectable RAS/BRAF wt mCRC from 20 China centers were randomly assigned (1:1) to receive up to 12 cycles biweekly mCapOX (capecitabine 1000mg/m 2 twice daily on Day 1-7 and oxaliplatin 85 mg/m 2 on Day 1) plus CET (500mg/m 2 ) (arm A) or mFOLFOX6 (oxaliplatin 85 mg/m 2 , leucovorin 200 mg/m 2 , fluorouracil 400mg/m 2 on day 1, and fluorouracil 2400 mg/m 2 over 46h) plus CET (500mg/m 2 ) (arm B) followed by maintenance (either capecitabine plus CET or capecitabine alone at the discretion of the investigators) or treatment-free intervals until progression on treatment, toxicity, or death. The primary endpoint was progression-free survival (PFS) rate at 9 months. This is an updated result with a median follow-up of 26.1 months and cost-effectiveness evaluation. Results: Between September 2021 and April 2024, 168 patients were enrolled in the intention-to-treat (ITT) population and 156 patients were included in the per-protocol (PP) population. In the ITT population, the 9 months-PFS rates were 67.9% (95% CI 58.6%-78.6%) in arm A and 61.9% (95% CI 52.3%-73.2%) in arm B, and the primary endpoint was met. The median PFS (arm A/B) was 11.6 months/10.8 months (P=0.183). The overall response rate (ORR) and disease control rate (DCR) in arm A were higher than those in arm B with 64.3% versus 56.0% and 90.5% versus 84.5%, respectively. The 2-year overall survival (OS) rate (arm A/B) was 75.8% vs 68.6%. The median OS was not reached in the arm A while it was 35.5 in the arm B. Grade≥3 adverse events (AEs) occurred in 26.1% of patients, with 15.0% in arm A and 37.0% in arm B. The most commonly Grade≥3 AEs was neutropenia, rash, and leukopenia and there were no grade 5 AEs reported. A cost-effectiveness analysis showed an incremental cost-effectiveness ratio of $19,067 per QALY for mCapOX + CET, below the Chinese willingness-to-pay threshold ($ 41,188/QALY). Conclusions: The CAPCET study met its primary endpoint. mCapOX + CET demonstrated higher ORR/DCR and 2-year OS, with reduced toxicity, compared to mFOLFOX6 + CET. These findings support mCapOX + cetuximab as a clinically effective, better-tolerated, and cost-effective first-line treatment for left-sided RAS/BRAF wild-type mCRC within the Chinese economic framework, providing rationale for ongoing phase III evaluation (NCT06616259). Clinical trial information: NCT05022030 .