First-Line Encorafenib Plus Binimetinib and Cetuximab Shows Promise in BRAF V600E+ mCRC

Despite having high-risk features, including age ≥65 years and advanced-stage disease at diagnosis, most patients receiving first-line encorafenib plus binimetinib and cetuximab for BRAFV600E-positive metastatic colorectal cancer (mCRC) in the ANCHOR CRC trial had tumor regression.

The findings of the study led by Axel Grothey, MD, West Cancer Center, University of Tennessee, Germantown, were presented at the virtual 22nd ESMO World Congress on Gastrointestinal Cancer.

“In patients with BRAFV600E-mutant mCRC, the combination of encorafenib plus cetuximab with or without binimetinib in second- and third-line therapy has demonstrated improved outcomes compared to standard therapies (BEACON CRC study),” explained Dr Grothey and colleagues, who conducted the open-label, 2-stage design ANCHOR CRC study to assess use of the triplet combination as first-line therapy in this patient population.

The primary end point of the study was the confirmed objective response rate (cORR), assessed via local review, and secondary end points included progression-free survival (PFS) and safety.

A total of 41 treatment-naïve patients with BRAFV600E-positive mCRC (median age, 67 years; 61% aged ≥65 years) were enrolled in Stage 1 of the single-arm, phase 2 study and given first-line encorafenib plus binimetinib and cetuximab, 40 of whom were deemed evaluable for efficacy. Specifically, patients received Patients received encorafenib 300 mg once daily, binimetinib 45 mg twice daily, and cetuximab 250mg/m² (after a first dose of 400mg/m²) for the first 28 weeks followed by 500mg/m² every 2 weeks.

At the point of study entry, 78% of patients had metastases to ≥2 organs and 51% had peritoneal metastasis.

The investigator-assessed cORR was found to be 50% (95% CI, 33.8-66.2), with tumor-size reduction observed in 85% of patients. In addition, the investigator-measured median PFS was 4.9 months (95% CI, 4.4-8.1).

According to the investigators, adverse events were consistent with those seen in prior studies of this triplet combination; 68% of patients had grade ≥3 adverse events, the most common of which were diarrhea (15%), acute kidney injury (12%), and anemia (12%).

“The ANCHOR CRC study is the first prospective study using a BRAF inhibitor-based therapy in first line BRAFV600E-mutant mCRC. Despite the high-risk features of the population enrolled in Stage 1, including high proportion of patients ≥65 years old and advanced stage at diagnosis, most patients had tumor regression,” Dr Grothey et al concluded.

“The safety profile was acceptable and toxicities remained manageable,” they added.—Hina M. Porcelli

Grothey A, Tabernero J, Taieb J, et al. ANCHOR CRC: a single-arm, phase 2 study of encorafenib, binimetinib plus cetuximab in previously untreated BRAF V600-mutant metastatic colorectal cancer. Presented at: the 22nd ESMO World Congress on Gastrointestinal Cancer; July 1-4, 2020; virtual. Abstract LBA-5.