PMID- 36653241
OWN - NLM
STAT- MEDLINE
DCOM- 20230321
LR  - 20230321
IS  - 1938-0674 (Electronic)
IS  - 1533-0028 (Linking)
VI  - 22
IP  - 1
DP  - 2023 Mar
TI  - Adverse Events Associated with Encorafenib Plus Cetuximab in Patients with 
      BRAFV600E-mutant Metastatic Colorectal Cancer: An in-depth Analysis of the BEACON 
      CRC Study.
PG  - 59-66
LID - S1533-0028(22)00134-7 [pii]
LID - 10.1016/j.clcc.2022.12.003 [doi]
AB  - BACKGROUND: The BRAF inhibitor encorafenib in combination with cetuximab was 
      recently approved for patients with BRAF(V600E)-mutated (BRAF(V600E)mut) 
      metastatic colorectal cancer (mCRC). Approval was based on positive results from 
      the phase 3 BEACON CRC study in BRAF(V600E)mut mCRC patients who had progressed 
      after 1-2 previous regimens. This analysis provides a detailed examination of the 
      adverse events (AEs) of interest (AEIs) with encorafenib+cetuximab in the BEACON 
      study to aid gastrointestinal oncologists, given the limited experience with this 
      combination. MATERIALS AND METHODS: AEIs, including dermatological AEs, 
      arthralgia/myalgia, nausea/vomiting, diarrhea, abdominal pain, fatigue/asthenia 
      and nephrotoxicity, were examined in the doublet therapy group. Clinical 
      characteristics associated with these AEs, AE grade, time to onset and time to 
      resolution were also studied. RESULTS: Safety analysis included 216/220 patients 
      randomized to doublet therapy. The most commonly occurring AEI was dermatological 
      toxicity (75.5%), followed by arthralgia/myalgia (56.0%) and fatigue/asthenia 
      (56.0%). Other than nephrotoxicity (7 patients; 5/7 with Grade 3 or 4), most AEs 
      were Grade 1 or 2. Most AEs were more common in women than men (nausea/vomiting, 
      diarrhea, abdominal pain, dermatological AEs, and arthralgia/myalgia). 
      Nausea/vomiting, abdominal pain and fatigue/asthenia were more common in patients 
      aged >/=70 years. Most AEs developed early, within the first 1-2 months of 
      treatment, and resolved within 1-2 weeks. In addition, survival outcomes were 
      better in patients experiencing arthralgia/myalgia or dermatological toxicities. 
      CONCLUSION: This analysis indicated that, except for rare cases of 
      nephrotoxicity, encorafenib+cetuximab is well tolerated in most patients, with 
      most AEIs being mild-to-moderate in severity, occurring early and resolving 
      rapidly. CLINICAL TRIAL REGISTRATION: the BEACON study (ClinicalTrials.gov, 
      NCT02928224; EudraCT, 2015-005805-35).
CI  - Copyright (c) 2022. Published by Elsevier Inc.
FAU - Taieb, Julien
AU  - Taieb J
AD  - Department of Gastroenterology and Digestive Oncology, Georges Pompidou European 
      Hospital, AP-HP, Universite Paris-Cite, SIRIC CARPEM, Paris University, Paris, 
      France. Electronic address: jtaieb75@gmail.com.
FAU - Lonardi, Sara
AU  - Lonardi S
AD  - Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
FAU - Desai, Jayesh
AU  - Desai J
AD  - Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, 
      Australia.
FAU - Folprecht, Gunnar
AU  - Folprecht G
AD  - Medical Dept. I, University Hospital Carl Gustav Carus, University Cancer Centre, 
      Dresden, Germany.
FAU - Gallois, Claire
AU  - Gallois C
AD  - Department of Gastroenterology and Digestive Oncology, Georges Pompidou European 
      Hospital, AP-HP, Universite Paris-Cite, SIRIC CARPEM, Paris University, Paris, 
      France.
FAU - Marques, Eduardo Polo
AU  - Marques EP
AD  - Miguel Servet University Hospital, Zaragoza, Spain.
FAU - Khan, Sadya
AU  - Khan S
AD  - Pierre Fabre, Boulogne-Billancourt, France.
FAU - Castagne, Claire
AU  - Castagne C
AD  - Pierre Fabre, Boulogne-Billancourt, France.
FAU - Wasan, Harpreet
AU  - Wasan H
AD  - Division of Cancer, Hammersmith Hospital, Imperial College London, London, United 
      Kingdom.
LA  - eng
SI  - ClinicalTrials.gov/NCT02928224
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20221224
PL  - United States
TA  - Clin Colorectal Cancer
JT  - Clinical colorectal cancer
JID - 101120693
RN  - 8L7891MRB6 (encorafenib)
RN  - PQX0D8J21J (Cetuximab)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
SB  - IM
MH  - Male
MH  - Humans
MH  - Female
MH  - Cetuximab
MH  - *Colorectal Neoplasms/drug therapy/genetics
MH  - Asthenia/chemically induced
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - Myalgia/chemically induced/drug therapy
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - *Colonic Neoplasms/drug therapy
MH  - *Rectal Neoplasms/drug therapy
MH  - Vomiting/chemically induced
MH  - Nausea/chemically induced
MH  - Fatigue/etiology
MH  - Mutation
OTO - NOTNLM
OT  - BRAF inhibitors
OT  - Biomarkers
OT  - Toxicity
OT  - enco+cetux
OT  - mCRC
EDAT- 2023/01/19 06:00
MHDA- 2023/03/22 06:00
CRDT- 2023/01/18 22:00
PHST- 2022/06/29 00:00 [received]
PHST- 2022/12/19 00:00 [revised]
PHST- 2022/12/21 00:00 [accepted]
PHST- 2023/01/19 06:00 [pubmed]
PHST- 2023/03/22 06:00 [medline]
PHST- 2023/01/18 22:00 [entrez]
AID - S1533-0028(22)00134-7 [pii]
AID - 10.1016/j.clcc.2022.12.003 [doi]
PST - ppublish
SO  - Clin Colorectal Cancer. 2023 Mar;22(1):59-66. doi: 10.1016/j.clcc.2022.12.003. 
      Epub 2022 Dec 24.