{"doi":"10.1038/s41591-024-03443-3","title":"Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial","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 .","journal":"Nature Medicine","year":2025,"id":508769,"datarank":1.3335205036637992,"base_score":4.6913478822291435,"endowment":4.6913478822291435,"self_citation_contribution":0.7037021823343717,"citation_network_contribution":0.6298183213294274,"self_endowment_contribution":0.7037021823343717,"citer_contribution":0.6298183213294274,"corpus_percentile":null,"corpus_rank":null,"citation_count":108,"citer_count":100,"citers_with_citation_signal":42,"citers_with_endowment":42,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04607421"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":310797,"name":"Takayuki Yoshino","orcid":"0000-0002-0489-4756","position":1,"is_corresponding":false},{"id":88015,"name":"Eric Van Cutsem","orcid":"0000-0002-6372-1230","position":2,"is_corresponding":false},{"id":332456,"name":"Cathy Eng","orcid":"0000-0003-2335-0612","position":3,"is_corresponding":false},{"id":1361024,"name":"Tae Won Kim","orcid":"0000-0001-9522-1997","position":4,"is_corresponding":false},{"id":1361011,"name":"Harpreet Wasan","orcid":"0000-0002-6268-2030","position":5,"is_corresponding":false},{"id":260048,"name":"Jayesh Desai","orcid":"0000-0003-4246-9344","position":6,"is_corresponding":false},{"id":999367,"name":"Fortunato Ciardiello","orcid":"0000-0002-4661-5540","position":7,"is_corresponding":false},{"id":90752,"name":"Rona Yaeger","orcid":"0000-0002-7233-5454","position":8,"is_corresponding":false},{"id":678552,"name":"Tim Maughan","orcid":"0000-0002-0580-5065","position":9,"is_corresponding":false},{"id":1361025,"name":"Elena Beyzarov","orcid":"0000-0002-6190-9432","position":10,"is_corresponding":false},{"id":1361026,"name":"Xiaoxi Zhang","orcid":"0009-0003-9923-9985","position":11,"is_corresponding":false},{"id":1362304,"name":"Graham Ferrier","orcid":null,"position":12,"is_corresponding":false},{"id":1361027,"name":"Xiaosong Zhang","orcid":"0009-0000-2415-5355","position":13,"is_corresponding":false},{"id":35283,"name":"Josep Tabernero","orcid":"0000-0002-2495-8139","position":14,"is_corresponding":false},{"id":241627,"name":"Scott Kopetz","orcid":"0000-0001-9647-3416","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:47:00.188082Z","pmid":"39863775","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}