Dr. Eng Breaks Down Braftovi Plus Erbitux FDA Approval in BRAF+ mCRC

In December 2024, the United States Food and Drug Administration (FDA) approved treatment with the combination of Braftovi (encorafenib) and Erbitux (cetuximab) plus chemotherapy for patients with metastatic colorectal cancer with a BRAF V600E mutation.

This FDA approval was supported by important data generated from the BREAKWATER trial which investigated the now-FDA-approved treatment in patients with treatment-naive BRAF V600E mutation-positive metastatic disease.

In an interview with CURE, Dr. Cathy Eng sat down to discuss the importance of the FDA approval, the BREAKWATER data and next steps for this treatment combination. Eng currently serves as the David H. Johnson Endowed Chair in Surgical and Medical Oncology; a professor of Medicine, Hematology and Oncology; and director for Strategic Relations, all at Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, located in Nashville, Tennessee. It is here that she is also the co-Director of GI Oncology; co-leader of the GI Cancer Research Program; and director of the Young Adult Cancers Program.

Transcript:

Just to give you some perspective of our metastatic colorectal cancer patient population, the presence of the BRAF V600E mutation has historically been associated with a poor prognosis in our MSI-stable patient population.

Previously, the addition of Braftovi, a BRAF inhibitor, plus Erbitux, an anti-EGFR inhibitor, in the previously treated setting, had already received FDA approval. This was based on improved overall survival compared with standard chemotherapy in the second or third-line setting. That survival was about 9.3 months, leading to the FDA approval of the doublet of Braftovi and Erbitux to provide a more tailored approach to our BRAF-mutated patients.

Now, these patients tend to have very metastatic disease, and we obviously want to help them as much as possible because they can become very symptomatic if not treated early on. So, how can we improve upon that original FDA indication? That is the purpose of the BREAKWATER trial.

The purpose of the BREAKWATER trial is to take that doublet of Braftovi and Erbitux and look at it in combination with chemotherapy to see if it's actually better than chemotherapy alone. The original study design also included one arm with the doublet by itself, but that was eventually discontinued. The main portion of the trial really focuses on chemotherapy with the FOLFOX or FOLFIRI (fluorouracil, leucovorin, oxaliplatin or irinotecan) backbone plus Braftovi and Erbitux. Is that better than standard chemotherapy?

You should be aware that a FOLFOXIRI arm was also added, and that trial has finished enrollment. We don't have those results yet. So, the purpose of the BREAKWATER FDA's new indication is the addition of chemotherapy in treatment-naive patients with a BRAF V600E mutation in their metastatic colorectal carcinoma, using oxaliplatin-based therapy (FOLFOX) or FOLFIRI plus Braftovi and Erbitux.

It showed an improved response rate, as well as, at the interim analysis, what looks like improved overall survival. So that is the new recent indication. The response rate was quite high, 60% versus 40%, so we are quite impressed with that. Once again, we are really trying to provide our best options for these patients who have a much more aggressive tumor type, which historically has resulted in poor overall survival.

Transcript has been edited for clarity and conciseness.

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