BREAKWATER: updated results of the safety lead-in

In this video Prof Dr Eric Van Cutsem (University Hospitals Leuven) and Prof Dr Scott Kopetz (MD Anderson Cancer Center, Houston, TX, USA) talk us through the updated results of the safety lead-in of the BREAKWATER trial presented at ESMO 2024.

BREAKWATER is an open label, multicenter, randomized, phase 3 study comparing the combination of encorafenib and cetuximab (EC) with or without chemotherapy (FOLFIRI or mFOLFOX6) to standard of care chemotherapy in patients with previously untreated BRAF^V600E mutant metastatic colorectal cancer (mCRC). During ESMO 2024, updated results were presented of the safety lead-in of this trial in which patients were treated with a combination of EC and FOLFIRI. In total, 12 patients received this regimen in first line, while 18 received it as second-line therapy.

Only one dose-limiting toxicity was reported in the study consisting of a grade 4 neutropenia that lasted for more than 7 days. Response data were very promising with an objective response rate of 83.3% and 44.4% for patient receiving the treatment in 1^st and 2^nd line, respectively. For patients who received the treatment in 1^st line, the median progression-free survival (PFS) was not yet reached, while this was reported at 12.6 months in patients receiving EC + FOLFIRI in second line. Commenting on these findings, Prof Kopetz underscored that these response and PFS data compare favorably to historical controls, where a typical median PFS of only about 6 months is seen in the second line setting. After about 31 months of follow up, the median overall survival (OS) was not yet reached in the first line cohort while this was 19.7 months among patients receiving the treatment in second line.

As such, these results support the continued evaluation of EC + FOLFIRI as a treatment option for patients with BRAF^V600E-mutant mCRC in cohort 3 of the BREAKWATER study.