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

Abstract

3563 Background: This CAPCET randomized phase II trial 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, multicenter, randomized, non-comparative phase II trial. Patients with unresectable RAS/BRAF wt mCRC were randomly assigned (1:1) to receive up to 12 cycles biweekly mCapOX (capecitabine 1000mg/m 2 orally twice daily on Day 1-7 and oxaliplatin 85 mg/m 2 iv on Day 1) plus CET (500mg/m 2 iv on day 1) (arm A) or biweekly mFOLFOX6 (oxaliplatin 85 mg/m 2 iv on day 1, leucovorin 400 mg/m 2 iv on day 1, fluorouracil 400mg/m 2 iv bolus on day 1, then fluorouracil 2400 mg/m 2 continuous infusion over 46-48h) plus CET (500mg/m 2 iv on day 1)(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 from randomization. Results: Between September 2021 and April 2024, 168 patients (84 in arm A and 84 in arm B) were enrolled in 20 China centres. Baseline characteristics were well balanced between arms. After a median follow-up of 21.0 months (IQR,19.5-22.5), the 9 months-PFS rates were 70.9% (95% CI 61.1%-82.3%) in arm A and 66.8% (95% CI 56.7%-78.6%; HR = 1.11, P = 0.558) in arm B, and the primary endpoint was met. The median PFS (arm A/B) was 12.7 months (95% CI 10.8–15.2)/12.0 months (95% CI 9.7–14.1). The overall response rate (ORR) and disease control rate (DCR) in arm A were higher than those in arm B with 69.2% versus 60.3% and 96.2% versus 89.7%, respectively. The 2-year overall survival (OS) rate (arm A/B) was 66.8% (95% CI 54.2%–82.3%)/65.6% (95% CI 52.5%–82.0%), and the median OS not reached. Grade≥3 adverse events (AEs) occurred in 28.8% of safety population set (n = 156), with 7.7% in arm A and 21.2% in arm B. The most commonly Grade≥3 AEs was neutropenia, rash, leukopenia and there were no grade 5 AEs reported. Conclusions: The CAPCET study met its first endpoint of 9-month PFS rate in patients with RAS/BRAF wt mCRC. Biweekly mCapOX plus CET had higher ORR and DCR than mFOLFOX6 plus CET, with signally reduced toxicity. Longer follows-up and a multicenter, open-label, randomized, controlled Phase CAPCET- III study (NCT06616259) will be further validate this innovative regimen. Clinical trial information: NCT05022030 .