Cetuximab, Encorafenib Combination Granted Expanded Label for Treatment of BRAF V600E Mutation-Positive Metastatic Colorectal Cancer

The FDA has approved an expanded label for the combination of cetuximab (Erbitux; Lilly) and encorafenib (Braftovi; Pfizer) for the treatment of metastatic colorectal cancer (CRC) with a BRAF V600E mutation following prior therapy.

The new indication makes cetuximab the first and only anti-EGFR antibody approved in combination with encorafenib for this indication, according to an Eli Lilly and Company press release. The approval is based on findings from BEACON CRC, which is the only phase 3 trial to specifically study patients with previously treated metastatic CRC with a BRAF V600E mutation.

“The BEACON study showed that the combination of Erbitux and encorafenib significantly improved overall survival in patients with metastatic colorectal cancer with a BRAF V600E mutation—a subtype that typically has worse outcomes compared to those without the mutation,” said David Hyman, MD, chief medical officer of oncology at Lilly, in the press release.

Colorectal cancer is the second leading cause of cancer death worldwide, with an estimated 1.9 million new diagnoses in 2020. BRAF mutations are estimated to occur in up to 15% of individuals with metastatic CRC and represent a poor prognosis for these patients. The BRAF V600E mutation is the most common BRAF mutation, with a twice-as-high risk of mortality for patients with this mutation compared to those with the wild-type BRAF.

The phase 3 BEACON CRC trial was a randomized, active-controlled, open-label, multicenter trial evaluating encorafenib and cetuximab. Patients were required to have BRAF V600E mutant metastatic CRC, as detected by an FDA-approved test, with disease progression after 1 or 2 prior regimens. They were randomized to receive either encorafenib 300 mg orally once daily in combination with cetuximab; encorafenib 300 mg orally once daily in combination with cetuximab and binimetinib; or irinotecan with cetuximab or Folfiri with cetuximab.

The trial found that the combination of cetuximab and encorafenib resulted in a median overall survival of 8.4 months, compared to 5.4 months in the control arm. Furthermore, according to the press release, cetuximab and encorafenib showed an objective response rate of 20% compared to 2% in the control arm, and a median progression-free survival of 4.2 months in the treatment arm compared to 1.5 months in the control arm.

The safety of the combination was evaluated in 216 patients with BRAF V600E mutation-positive metastatic CRC in the BEACON CRCC trial. The most common adverse events in patients receiving the combination were fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, and rash.

Labeling for cetuximab includes warnings and precautions for infusion reactions, cardiopulmonary arrest, pulmonary toxicity, dermatologic toxicity, hypomagnesemia and accompanying electrolyte abnormalities, and embryo-fetal toxicity. Encorafenib was approved by the FDA for this indication in April 2020, based on data from the BEACON CRC trial.

REFERENCE

FDA Expands Lilly’s Erbitux (cetuximab) Label with Combination for BRAFTOVI (encorafenib) for the Treatment of BRAF V600E Mutation-Positive Metastatic Colorectal Cancer (CRC) after Prior Therapy. News release. Lilly; September 28, 2021. Accessed September 29, 2021. https://investor.lilly.com/news-releases/news-release-details/fda-expands-lillys-erbituxr-cetuximab-label-combination