Colon to Rectum

J Clin Oncol. 2024;42(11):1278–87

Pinto C, Orlandi A, Normanno N, Maiello E, Calegari MA, Antonuzzo L, Bordonaro R, Zampino MG, Pini S, Bergamo F, Tonini G, Avallone A, Latiano TP, Rosati G, Cogoni AA, Ballestrero A, Zaniboni A, Roselli M, Tamberi S, Barone C

Fluorouracil, leucovorin, and irinotecan plus cetuximab versus cetuximab as maintenance therapy in first-line therapy for RAS and BRAF wild-type metastatic colorectal cancer: Phase 3 ERMES study

Purpose: The intensity of anti-epidermal growth factor receptor (EGFR)-based first-line therapy for RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC), once disease control is achieved, is controversial. A de-escalation strategy with anti-EGFR monotherapy represents a potential option to maintain efficacy while reducing cytotoxicity.
Methods: In this multicenter, open-label, phase 3 trial, patients with untreated RAS/BRAF wt mCRC were randomly assigned to receive either fluorouracil, leucovorin, and irinotecan/cetuximab (FOLFIRI/Cet) until disease progression (arm A) or FOLFIRI/Cet for 8 cycles followed by Cet alone (arm B). The co-primary end points were a non-inferior progression-free survival (PFS) in the modified per-protocol (mPP) population (> 8 cycles) and a lower incidence of grade (G) 3–4 adverse events (AEs) for arm B compared with arm A.
Results: Overall, 606 patients were randomly assigned, with 300 assigned to arm A and 306 to arm B. The median follow-up was 22.3 months. In the mPP population, 291 events occurred with a PFS of 10 versus 12.2 months for arms B and A, respectively (p of non-inferiority = 0.43). In the intention-to-treatment (ITT, ≥ 1 cycle) population, 503 events occurred with a PFS of 9 versus 10.7 months (p = 0.39). The overall survival was 35.7 versus 30.7 months (p = 0.119) and 31.0 versus 25.2 months (p = 0.32) in the mPP and ITT population, respectively. Arm B had lower G3–4 AEs during the maintenance period than arm A (20.2% vs. 35.1%).

Conclusion: The ERMES study did not demonstrate non-inferiority of maintenance with cetuximab (Cet) alone. Despite a more favorable safety profile, maintenance with single-agent Cet after induction with FOLFIRI/Cet cannot be recommended for all patients but could represent an option in selected cases.

DOI: 10.1200/jco.23.01021