Elena Elez, MD, PhD, on Updated Survival Data From the BREAKWATER Trial
2025 ASCO Annual Meeting
Elena Elez, MD, PhD, of Vall d’Hebron Institute of Oncology, presents updated overall survival data as well as progression-free survival data from the BREAKWATER trial of the first-line use of encorafenib, cetuximab, and mFOLFOX6 in BRAF V600E–mutant metastatic colorectal cancer (LBA3500).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
We know that between 8 to 12% of patients with metastatic colorectal cancer have BRAF V600E–mutated metastatic colorectal cancer. What we know from these illnesses is that it's a poor prognosis group of patients, so the first-line treatments that we have have really limited efficacy, and this was the basis for developing a phase three clinical trial in this patient population. We know as well that encorafenib is an ATP-competitive BRAF inhibitor that, combined with cetuximab, was approved for treatment in the second and third line of metastatic colorectal cancer in this patient population. What we are doing now is exploring the combination of encorafenib, cetuximab, and FOLFOX in frontline therapy for this patient population, compared to encorafenib and cetuximab alone or the standard of care, which is chemotherapy combined with bevacizumab or not. The dual primary endpoint of this clinical trial was progression-free survival and overall response rate, and the secondary objective of this clinical trial was overall survival. Indeed, the results of the BREAKWATER trial were presented at the beginning of 2025. We had the results of overall response rate—the study met one of its primary endpoints—and what we are presenting now at ASCO 2025 are the results of progression-free survival, the other dual primary endpoint, and results on overall survival. Regarding the patient population, it was well balanced. It's nice to see that we have a representation of patients with high tumor burden, meaning three or more metastatic sites of metastasis as well as liver metastasis. Regarding the results on overall survival, the combination of FOLFOX, encorafenib, and cetuximab was statistically significant and clinically meaningful, superior compared to the standard of care. In this case, we found 30 months of overall survival for the patients treated with encorafenib, cetuximab, and FOLFOX, and 15 months for those patients treated with the standard of care. This represents a paradigm change in the treatment of metastatic colorectal cancer harboring a BRAF V600E mutation, and this regimen will be a new standard of care in the frontline setting for this patient population.
The ASCO Post Staff
Stuart J. Wong, MD, of the Medical College of Wisconsin and Plenary discussant, reviews findings from the phase III NIVOPOSTOP randomized trial, which investigated the adjuvant use of nivolumab added to radiochemotherapy for patients with resected head and neck squamous cell carcinoma who are at high risk of relapse (LBA2).
The ASCO Post Staff
Sameek Roychowdhury, MD, PhD, of the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at The Ohio State University Wexner Medical Center, discusses a recently opened telemedicine clinical trial of pemigatinib in patients with advanced or metastatic FGFR-mutated pancreatic cancer, and the germination of a new initiative, TNT Cancer, which focuses on leveraging telemedicine to bring trials nationwide.
The ASCO Post Staff
William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center, reviews the final analysis of phase II CAPTIVATE study demonstrating the long-term efficacy and safety of ibrutinib plus venetoclax for previously untreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including in patients with high-risk genomic features. The 5.5-year progression-free survival and overall survival rates were 66% and 97%, respectively (Abstract 7036).
The ASCO Post Staff
Mafalda Oliveira, MD, PhD, of Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, discusses findings on the incidence and management of hyperglycemia in a subset of patients with prediabetes and/or obesity included in the phase I trial of inavolisib alone and in combination with endocrine therapy with or without palbociclib for PIK3CA-mutated, hormone receptor–positive, HER2-negative locally advanced/metastatic breast cancer (Abstract 1004).
The ASCO Post Staff
Alicia Latham, MD, MS, of Memorial Sloan Kettering Cancer Center, discusses the feasibility of using Pap-derived ctDNA for the detection of sporadic and Lynch syndrome–associated endometrial cancer (Abstract 10503).