Rona Yaeger

Jan 25, 2025 | nature.com | Scott Kopetz |Takayuki Yoshino |Eric Van Cutsem |Cathy Eng |Harpreet Wasan |Jayesh Desai | +9 more

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 . As presented at the 2025 ASCO GI Cancers Symposium: in the phase 3 BREAKWATER trial, patients with previously untreated BRAF V600E metastatic colorectal cancer received the BRAF inhibitor encorafenib, the anti-EGFR monoclonal antibody cetuximab and chemotherapy mFOLFOX6 versus investigator’s choice of chemotherapy with or without bevacizumab, leading to an improved objective response rate, with the dual primary endpoint of progression free survival still maturing.

Jan 9, 2025 | nature.com | Melissa Lumish |Saskia Hartner |Sasha Balkaran |Jonathan Bermeo |Simran Asawa |Asha Saxena | +12 more

Correction to: Nature https://doi.org/10.1038/s41586-024-08150-0 Published online 30 October 2024In the version of this article initially published, initials were used instead of the authors’ given names, and the second affiliation shown for Emmanouil Pappou (Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA) was incorrect. The names and affiliation have been amended in the HTML and PDF versions of the article.

Sep 23, 2024 | nature.com | Scott Kopetz |Fortunato Ciardiello |Jayesh Desai |Takayuki Yoshino |Tao Xie |Rona Yaeger

AbstractThe BEACON CRC study demonstrated that encorafenib (Enco)+cetuximab (Cetux)±binimetinib (Bini) significantly improved overall survival (OS) versus Cetux + chemotherapy in previously treated patients with BRAF-V600E-mutant mCRC, providing the basis for the approval of the Enco+Cetux regimen in the United States and the European Union. A greater understanding of biomarkers predictive of response to Enco+Cetux±Bini treatment is of clinical relevance.

Sep 9, 2024 | digitalcommons.library.tmc.edu | Yasutoshi Kuboki |Marwan Fakih |John Strickler |Rona Yaeger

The current third-line (and beyond) treatment options for RAS-mutant metastatic colorectal cancer have yielded limited efficacy. At the time of study start, the combination of sotorasib, a KRAS (Kirsten rat sarcoma viral oncogene homolog)-G12C inhibitor, and panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, was hypothesized to overcome treatment-induced resistance.

Feb 26, 2024 | onclive.com | Rona Yaeger

Rona Yaeger, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, discusses the future implications of findings from an expansion cohort study of sotorasib (Lumakras) plus panitumumab (Vectibix) in the second-line setting patients with KRAS G12C–mutated metastatic colorectal cancer (mCRC).