PMID- 38181312
OWN - NLM
STAT- MEDLINE
DCOM- 20240408
LR  - 20240410
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 42
IP  - 11
DP  - 2024 Apr 10
TI  - 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 III ERMES Study.
PG  - 1278-1287
LID - 10.1200/JCO.23.01021 [doi]
AB  - 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.
FAU - Pinto, Carmine
AU  - Pinto C
AUID- ORCID: 0000-0002-3159-5268
AD  - Medical Oncology, Comprehensive Cancer Centre Azienda USL-IRCCS di Reggio Emilia, 
      Reggio Emilia, Italy.
FAU - Orlandi, Armando
AU  - Orlandi A
AUID- ORCID: 0000-0001-5253-4678
AD  - Comprehensive Cancer Center, UOC Medical Oncology, Fondazione Policlinico 
      Universitario Agostino Gemelli IRCCS, Roma, Italy.
FAU - Normanno, Nicola
AU  - Normanno N
AUID- ORCID: 0000-0002-7158-2605
AD  - Translational Research Departement, Istituto Nazionale Tumori IRCCS-Fondazione G. 
      Pascale, Napoli, Italy.
FAU - Maiello, Evaristo
AU  - Maiello E
AUID- ORCID: 0000-0003-3890-3435
AD  - Oncology Unit, Foundation IRCCS Casa Sollievo della Sofferenza, San Giovanni 
      Rotondo, Italy.
FAU - Calegari, Maria A
AU  - Calegari MA
AUID- ORCID: 0000-0001-6856-2593
AD  - Comprehensive Cancer Center, UOC Medical Oncology, Fondazione Policlinico 
      Universitario Agostino Gemelli IRCCS, Roma, Italy.
FAU - Antonuzzo, Lorenzo
AU  - Antonuzzo L
AD  - Department of Experimental and Clinical Medicine, University of Florence, Italy 
      Clinical Oncology Unit, Careggi University Hospital, Firenze, Italy.
FAU - Bordonaro, Roberto
AU  - Bordonaro R
AUID- ORCID: 0000-0001-5005-0880
AD  - Medical Oncology, Azienda Ospedaliera ARNAS Garibaldi, Catania, Italy.
FAU - Zampino, Maria G
AU  - Zampino MG
AD  - Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European 
      Institute of Oncology, IRCCS, Milan, Italy.
FAU - Pini, Sara
AU  - Pini S
AD  - Ospedale Santa Maria delle Croci, Ravenna, Italy.
FAU - Bergamo, Francesca
AU  - Bergamo F
AUID- ORCID: 0000-0002-8795-4653
AD  - Dipartimento Oncologia 1, IOV-Istituto Oncologico Veneto IRCCS, Padova, Italy.
FAU - Tonini, Giuseppe
AU  - Tonini G
AUID- ORCID: 0000-0003-4442-8677
AD  - Dipartimento di Oncologia, Fondazione Policlinico Campus Bio-Medico, Facolta di 
      Medicina Universita Campus Bio-Medico, Rome, Italy.
FAU - Avallone, Antonio
AU  - Avallone A
AUID- ORCID: 0000-0001-6188-5664
AD  - Medical Oncology, Istituto Nazionale Tumori-IRCCS Fondazione G. Pascale, Naples, 
      Italy.
FAU - Latiano, Tiziana P
AU  - Latiano TP
AD  - Oncology Unit, Foundation IRCCS Casa Sollievo della Sofferenza, San Giovanni 
      Rotondo, Italy.
FAU - Rosati, Gerardo
AU  - Rosati G
AUID- ORCID: 0000-0001-7004-6862
AD  - Medical Oncology Unit, S. Carlo Hospital, Potenza, Italy.
FAU - Cogoni, Alessio Aligi
AU  - Cogoni AA
AUID- ORCID: 0000-0002-5852-1509
AD  - UO Oncologia AOU Sassari, Sassari, Italy.
FAU - Ballestrero, Alberto
AU  - Ballestrero A
AD  - DiMI Universita degli Studi di Genova e Ospedale Policlinico San Martino IRCCS, 
      Genova, Italy.
FAU - Zaniboni, Alberto
AU  - Zaniboni A
AD  - Medical Oncology Unit, Fondazione Poliambulanza, Brescia, Italy.
FAU - Roselli, Mario
AU  - Roselli M
AD  - Medical Oncology Unit, Department of Systems Medicine, University of Rome Tor 
      Vergata, Rome, Italy.
FAU - Tamberi, Stefano
AU  - Tamberi S
AD  - UO Medical Oncology, Area Vasta Romagna Ausl di Ravenna, Presidio Ospedaliero di 
      Faenza, Ospedale Civile degli Infermi, Faenza, Italy.
FAU - Barone, Carlo
AU  - Barone C
AUID- ORCID: 0000-0002-9026-8953
AD  - Comprehensive Cancer Center, UOC Medical Oncology, Fondazione Policlinico 
      Universitario Agostino Gemelli IRCCS, Roma, Italy.
LA  - eng
SI  - ClinicalTrials.gov/NCT02484833
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
DEP - 20240105
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - XT3Z54Z28A (Camptothecin)
RN  - PQX0D8J21J (Cetuximab)
RN  - U3P01618RT (Fluorouracil)
RN  - 7673326042 (Irinotecan)
RN  - Q573I9DVLP (Leucovorin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
SB  - IM
MH  - Humans
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Camptothecin/adverse effects
MH  - Cetuximab/adverse effects
MH  - *Colonic Neoplasms/drug therapy
MH  - *Colorectal Neoplasms/drug therapy/genetics
MH  - Fluorouracil/adverse effects
MH  - Irinotecan/therapeutic use
MH  - Leucovorin/adverse effects
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - *Rectal Neoplasms/drug therapy
EDAT- 2024/01/05 18:41
MHDA- 2024/04/08 06:42
CRDT- 2024/01/05 16:03
PHST- 2024/04/08 06:42 [medline]
PHST- 2024/01/05 18:41 [pubmed]
PHST- 2024/01/05 16:03 [entrez]
AID - 10.1200/JCO.23.01021 [doi]
PST - ppublish
SO  - J Clin Oncol. 2024 Apr 10;42(11):1278-1287. doi: 10.1200/JCO.23.01021. Epub 2024 
      Jan 5.