Author(s): Carmine Pinto, MD1; Armando Orlandi, MD, PhD2; Nicola Normanno, MD, PhD3; Evaristo Maiello, MD4; Maria A. Calegari, MD, PhD2; Lorenzo Antonuzzo, MD, PhD5; Roberto Bordonaro, MD6; Maria G. Zampino, MD7; Sara Pini, MD8; Francesca Bergamo, MD9; Giuseppe Tonini, MD10; Antonio Avallone, MD11; Tiziana P. Latiano, MD4; Gerardo Rosati, MD12; Alessio Aligi Cogoni, MD13; Alberto Ballestrero, MD14; Alberto Zaniboni, MD15; Mario Roselli, MD16; Stefano Tamberi, MD17; Carlo Barone, MD2
PURPOSE
The intensity of anti-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 III 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 eight cycles followed by Cet alone (arm B). The coprimary end points were a noninferior progression-free survival (PFS) in the modified per-protocol (mPP) population (>eight 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 noninferiority = .43). In the intention-to-treatment (ITT, ≥one cycle) population, 503 events occurred with a PFS of 9 versus 10.7 months (P = .39). The overall survival was 35.7 versus 30.7 months (P = .119) and 31.0 versus 25.2 months (P = .32) in the mPP and ITT population, respectively. Arm B had lower G3-4 AEs during the maintenance period than arm A (20.2% v 35.1%).
CONCLUSION
The ERMES study did not demonstrate noninferiority of maintenance with 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.
Author Affiliations
1Medical Oncology, Comprehensive Cancer Centre Azienda USL—IRCCS di Reggio Emilia, Reggio Emilia, Italy; 2Comprehensive Cancer Center, UOC Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy; 3Translational Research Departement, Istituto Nazionale Tumori IRCCS—Fondazione G. Pascale, Napoli, Italy; 4Oncology Unit, Foundation IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; 5Department of Experimental and Clinical Medicine, University of Florence, Italy Clinical Oncology Unit, Careggi University Hospital, Firenze, Italy; 6Medical Oncology, Azienda Ospedaliera ARNAS Garibaldi, Catania, Italy; 7Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy; 8Ospedale Santa Maria delle Croci, Ravenna, Italy; 9Dipartimento Oncologia 1, IOV—Istituto Oncologico Veneto IRCCS, Padova, Italy; 10Dipartimento di Oncologia, Fondazione Policlinico Campus Bio-Medico, Facoltà di Medicina Università Campus Bio-Medico, Rome, Italy; 11Medical Oncology, Istituto Nazionale Tumori-IRCCS Fondazione G. Pascale, Naples, Italy; 12Medical Oncology Unit, S. Carlo Hospital, Potenza, Italy; 13UO Oncologia AOU Sassari, Sassari, Italy; 14DiMI Università degli Studi di Genova e Ospedale Policlinico San Martino IRCCS, Genova, Italy; 15Medical Oncology Unit, Fondazione Poliambulanza, Brescia, Italy; 16Medical Oncology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; 17UO Medical Oncology, Area Vasta Romagna Ausl di Ravenna, Presidio Ospedaliero di Faenza, Ospedale Civile degli Infermi, Faenza, Italy
