KEY TAKEAWAYS
- The BEACON study (phase 3) demonstrated that the combination of encorafenib and cetuximab was approved for the treatment of previously treated patients with BRAFV600E mCRC, with a mPFS of 4.3 months and an ORR of 19.5%.
- The ANCHOR study (phase 2) evaluated the combination of encorafenib and binimetinib as a first-line treatment for BRAFV600E mCRC, demonstrating an mPFS of 5.8 months and an ORR of 48%.
- The ongoing phase 3 BREAKWATER study (NCT04607421) is assessing the efficacy of EC ± chemotherapy versus standard-of-care chemotherapy in BRAFV600E mCRC as a first-line approach.
- The BREAKWATER SLI included patients with BRAFV600E mCRC who had received ≤1 prior systemic treatment and excluded those previously treated with BRAFi/EGFRi or both oxaliplatin and irinotecan.
- Patients received encorafenib and cetuximab with either mFOLFOX6 or FOLFIRI in 28-day cycles until disease progression or unacceptable toxicity.
- The primary endpoint of the BREAKWATER SLI was the frequency of dose-limiting toxicities, with secondary endpoints including safety, pharmacokinetics, and antitumor activity. Updated results will include overall safety and tolerability, antitumor activity, and changes in BRAFV600EctDNA and MSI status of patients.
The combination of the BRAF inhibitor encorafenib (E) and the EGFR inhibitor cetuximab (C) was approved for the treatment of previously treated patients with BRAFV600E mCRC based on the results of the phase 3 BEACON study (NCT02928224), which showed a median progression-free survival (mPFS) of 4.3 months and an overall response rate (ORR) of 19.5%. The overall response rate (ORR) with 1L EC + binimetinib in BRAFV600E mCRC was 48%, and the median progression-free survival (mPFS) was 5.8 months in the ANCHOR study (NCT03693170).
The ongoing phase 3 BREAKWATER research (NCT04607421) compares EC chemotherapy to standard-of-care chemotherapy in BRAFV600E mCRC, providing additional information on 1L methods. Here they give the most recent information on BREAKWATER SLI biomarkers, as well as safety and anticancer efficacy. Participants in the SLI had to have BRAFV600E mCRC (either in their blood or tumour tissue), have received at least one prior systemic tx for mCRC, and have an ECOG performance status of 0 or 1. Those who had had BRAFi/EGFRi therapy or oxaliplatin and irinotecan in the past were not eligible.
Patients (n=27) received mFOLFOX6 every 2 weeks (Q2W) and (n=30) received FOLFIRI Q2W until disease progression or intolerable toxicity while receiving E 300 mg daily + C 500 mg/m2. The incidence of dose-limiting toxicities served as the key measure of success. Antitumor activity, pharmacokinetics, and safety were all considered secondary objectives. Plasma (circulating tumour DNA [ctDNA] genomic profiling) and tumour tissue (molecular profiling) biomarkers were evaluated as exploratory objectives.
The latest data on the BREAKWATER SLI’s efficacy, side effects, and ability to fight cancer will be discussed. Other biomarker information, such as post-treatment changes in BRAFV600EctDNA (on Days 15 and 7 of Cycle 1) and MSI status, will also be shared. The ultimate abstract will include the anticipated findings.
Source: https://meetings.asco.org/abstracts-presentations/215995
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT04607421
Kopetz, S., Yoshino, T., Kim, T.W., Yaeger, R., Desai, J., Wasan, H.S., Van Cutsem, E., Ciardiello, F., Maughan, T., Eng, C., Tie, J., Elez, E., Lonardi, S., Zhang, X., Chung, C.-H., Usari, T., Nicholz, T., Murphy, D.A. and Tabernero, J. (2023). BREAKWATER safety lead-in (SLI): Encorafenib (E) + cetuximab (C) + chemotherapy for BRAFV600E metastatic colorectal cancer (mCRC).. Journal of Clinical Oncology, 41(4_suppl), pp.119–119. doi:https://doi.org/10.1200/jco.2023.41.4_suppl.119.
