Trial reportNature medicine2025
Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.
Trial report in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04607421 (AN OPEN-LABEL, MULTICENTER, RANDOMIZED PHASE 3 STUDY OF FIRST-LINE ENCORAFENIB PLUS CETUXIMAB WITH OR WITHOUT CHEMOTHERAPY VERSUS STANDARD OF CARE THERAPY WITH A SAFETY LEAD-IN OF ENCORAFENIB AND CETUXIMAB PLUS CHEMOTHERAPY IN PARTICIPANTS WITH METASTATIC BRAF V600E-MUTANT COLORECTAL CANCER), which is not on this map. Cited by 72 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An open-label, multicenter, randomized phase 3 study of first-line encorafenib plus cetuximab with or without chemotherapy versus standard of care therapy with a safety lead-in of encorafenib and cetuximab plus chemotherapy in participants with metastatic braf v600e-mutant colorectal cancer
Who cites it
72 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- KRAS G12C inhibitors in KRASFrontiers in immunology · 2026Pooled it
- Defining the Prognostic Significance of BRAF V600E in Early-Stage Colon Cancer: A Systematic Review and Meta-Analysis.Current oncology (Toronto, Ont.) · 2025Pooled it
- Total neoadjuvant chemotherapy combined with PD‑1 blockade and IL‑2 in MSS/pMMR locally advanced rectal cancer: short-term results of a prospective, single-arm phase II study.Signal transduction and targeted therapy · 2026Trial
- BREAKWATER Phase III: results for encorafenib and cetuximab plus mFOLFOX6 in first-lineFuture oncology (London, England) · 2025Trial
- Encorafenib, Cetuximab, and mFOLFOX6 inThe New England journal of medicine · 2025Trial
- Colorectal Cancer: Epidemiology, Risk Factors, Signaling Pathways, Clinical Features, Screening, Diagnosis, and Management.MedComm · 2026Review
- Integrated clinicogenomic analysis reveals the evolution and metastatic tropisms of advanced colorectal cancer.Cancer cell · 2026Article
- [Personalized pharmacotherapy of colorectal cancer].Innere Medizin (Heidelberg, Germany) · 2026Article
- A multicenter survey on BRAF screening for the implementation of perioperative cancer genomic medicine for resectable colorectal oligometastases.International journal of clinical oncology · 2026Article
- Exceptional treatment responses and molecular markers among 103 colorectal cancer cell lines.Molecular biomedicine · 2026Article
- The Role of Monoclonal Antibody Targeted Therapy (Panitumumab) in the Treatment of Metastatic Colorectal Cancer-A Narrative Review of Current Evidence and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Beyond the biopsy: the new era of non-invasive staging and biomarkers in colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- CDK9 inhibition sensitizes intrinsically resistantActa pharmaceutica Sinica. B · 2026Article
- Gasdermin-Mediated Pyroptosis: Novel Strategies Against Colorectal Cancer.Cancer science · 2026Review
- Optimal First-Line Immunotherapy for MSI-H/dMMR Metastatic Colorectal Cancer: Evidence, Gaps, and Clinical Decision-Making.Journal of gastrointestinal cancer · 2026Review
- The State of the Art on Management of Patients with Unresectable Liver Metastases from Colorectal Cancer.Biomedicines · 2026Review
- Article
- Updates of CSCO guidelines for colorectal cancer version 2026.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026Article
- Review
- Alcohol consumption and molecular subtypes of colorectal cancer: pooled observational and Mendelian randomization analyses.The American journal of clinical nutrition · 2026Observational
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC. The dual primary endpoint of progression-free survival is event driven; data were not mature at data cutoff. BREAKWATER met the other dual primary endpoint of objective response rate, demonstrating significant and clinically relevant improvement in objective response rate (EC+mFOLFOX6: 60.9%; SOC: 40.0%; odds ratio, 2.443; 95% confidence interval (CI): 1.403-4.253; 99.8% CI: 1.019-5.855; one-sided P = 0.0008). Median duration of response was 13.9 versus 11.1 months. At this first interim analysis of overall survival, the hazard ratio was 0.47 (95% CI: 0.318-0.691; repeated CI: 0.166-1.322). Serious adverse event rates were 37.7% versus 34.6%. The safety profiles were consistent with those known for each agent. BREAKWATER demonstrated a significantly improved response rate that was durable for first-line EC+mFOLFOX6 versus SOC in patients with BRAF V600E mCRC. ClinicalTrials.gov identifier: NCT04607421 .
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.