Effect of invitation to colonoscopy versus faecal immunochemical test screening on colorectal cancer mortality (COLONPREV): a pragmatic, randomised, controlled, non-inferiority trial
People prefer stool card over colonoscopy, and it is not inferior.
Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer
Author(s): Elena Elez, M.D., Ph.D.1,2; Takayuki Yoshino, M.D., Ph.D.3; Lin Shen, M.D.4; Sara Lonardi, M.D.5; Eric Van Cutsem, M.D., Ph.D.6,7; Cathy Eng, M.D.8; Tae Won Kim, M.D., Ph.D.9; Harpreet Singh Wasan, M.D.10; Jayesh Desai, F.R.A.C.P.11,12; Fortunato Ciardiello, M.D., Ph.D.13; Rona Yaeger, M.D.14; Timothy S. Maughan, M.D.15; Van K. Morris, M.D.16; Christina Wu, M.D.17; Tiziana Usari, B.Sc.18; Robert Laliberte, M.S.19; Samuel S. Dychter, M.D.20; Xiaosong Zhang, M.D., Ph.D.21; Josep Tabernero, M.D., Ph.D.1,2,22; Scott Kopetz, M.D., Ph.D.16; for the BREAKWATER Trial Investigators*;
Source: DOI: 10.1056/NEJMoa2501912
Dr. Anjan Patel's Thoughts
The BREAKWATER trial evaluated encorafenib, cetuximab, and mFOLFOX6 as a first-line therapy for BRAF V600E–mutated metastatic colorectal cancer, showing very significant improvements in progression-free survival (PFS) (12.8 vs 7.1mos) and overall survival (OS) (30.3 vs 15.1mos). The combo also achieved a higher overall response rate (ORR). (60 vs 40%), positioning it as a new standard for this challenging patient population. Of note, side effects like nausea, diarrhea, and neuropathy, which were more frequent with this regimen. I would use this in the appropriate patient.
BACKGROUND
First-line treatment with encorafenib plus cetuximab (EC) with or without chemotherapy (oxaliplatin, leucovorin, and fluorouracil [mFOLFOX6]) for BRAF V600E–mutated metastatic colorectal cancer, an aggressive subtype with a poor prognosis, was compared with standard care (chemotherapy with or without bevacizumab) in an open-label, phase 3 trial, which showed significance regarding one of the two primary end points, objective response according to blinded independent central review (odds ratio for EC+mFOLFOX6 vs. standard care, 2.44; one-sided P<0.001). This result led to accelerated Food and Drug Administration approval of this investigational combination therapy for BRAF V600E–mutated metastatic colorectal cancer, including as first-line therapy. Data on progression-free survival (the second primary end point) and an updated interim analysis of overall survival are now available.
METHODS
We randomly assigned patients with untreated BRAF V600E–mutated metastatic colorectal cancer to receive EC, EC+mFOLFOX6, or standard care. The two primary end points were objective response (reported previously) and progression-free survival according to blinded independent central review in the EC+mFOLFOX6 group and the standard-care group. The key secondary end point was overall survival.
RESULTS
Significantly longer progression-free survival was seen with EC+mFOLFOX6 than with standard care (median, 12.8 vs. 7.1 months; hazard ratio for progression or death, 0.53; 95% confidence interval [CI], 0.41 to 0.68; P<0.001). In an interim analysis, overall survival was significantly longer with EC+mFOLFOX6 than with standard care (median, 30.3 vs. 15.1 months; hazard ratio for death, 0.49; 95% CI, 0.38 to 0.63; P<0.001). The incidence of serious adverse events during treatment was 46.1% with EC+mFOLFOX6 and 38.9% with standard care. Safety profiles were consistent with those known for each agent.
CONCLUSIONS
This trial showed significantly longer progression-free survival and overall survival with first-line treatment with EC+mFOLFOX6 than with standard care among patients with BRAF V600E–mutated metastatic colorectal cancer. (Funded by Pfizer and others; BREAKWATER ClinicalTrials.gov number, NCT04607421.)
Author Affiliations
1Vall d’Hebron Hospital Campus, Barcelona; 2Vall d’Hebron Institute of Oncology, Barcelona; 3National Cancer Center Hospital East, Kashiwa, Japan; 4Beijing Cancer Hospital, Beijing; 5Veneto Institute of Oncology, IRCCS, Padua, Italy; 6University Hospitals Gasthuisberg Leuven, Leuven, Belgium; 7KU Leuven, Leuven, Belgium; 8Vanderbilt-Ingram Cancer Center, Nashville; 9Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; 10Hammersmith Hospital, Division of Cancer, Imperial College London, London; 11Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; 12University of Melbourne, Melbourne, VIC, Australia; 13University of Campania Luigi Vanvitelli, Naples, Italy; 14Memorial Sloan Kettering Cancer Center, New York; 15University of Liverpool, Liverpool, United Kingdom; 16University of Texas M.D. Anderson Cancer Center, Houston; 17Mayo Clinic, Phoenix, AZ; 18Pfizer, Milan; 19Pfizer, Cambridge, MA; 20Pfizer, La Jolla, CA; 21Pfizer, South San Francisco, CA; 22University of Vic–Central University of Catalonia, Barcelona;Related Articles
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Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial
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Combination beat monotherapy is another option for MSI patients. Is combo better then pembro?
Nivolumab plus Ipilimumab in Microsatellite-Instability–High Metastatic Colorectal Cancer
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