Dr Imanirad on Toxicity Management for Encorafenib Plus Cetuximab in BRAF-Mutant mCRC

Iman Imanirad, MD, medical oncologist, gastrointestinal oncology, Moffitt Cancer Center, discusses the management of toxicities associated with standard-of-care encorafenib (Braftovi) plus cetuximab (Erbitux) for patients with previously treated microsatellite stable (MSS) BRAF V600E–mutated metastatic colorectal cancer (mCRC).

This doublet therapy was approved by the FDA for patients with mCRC expressing a BRAF V600E mutation in 2020. This regulatory decision was based on findings from the phase 3 BEACON CRC trial (NCT02928224). Patients enrolled onto the BEACON CRC trial were randomly assigned in a 1:1:1 ratio to receive the encorafenib plus cetuximab doublet; a triplet regimen containing encorafenib plus cetuximab and binimetinib; or the investigators’ choice of either cetuximab and irinotecan or cetuximab and FOLFIRI (leucovorin, fluorouracil, and irinotecan).

Both the doublet and triplet regimens significantly improved survival and response rates vs the control in this patient population. Grade 3 or higher adverse effects (AE) occurred in 58% of patients in the triplet-therapy group, in 50% in the doublet-therapy group, and in 61% in the control group.

Overall, the BEACON regimen exhibits a lower incidence of skin toxicity–a common AE associated with anti-EGFR monoclonalantibodies–compared with that of panitumumab (Vectibix) and cetuximab in earlier trials, Imanirad states. He notes that therate of grade 3/4 skin toxicity, notably acneiform dermatitis, in those trials was around 10% to 12%. The reduced likelihood of significant skin toxicity with the BEACON regimen may be attributed to its interaction with, and inhibition of, the BRAF pathway in the skin, Imanirad explains.

Given the lower probability of clinically significant skin toxicity, the administration of prophylactic therapy is not typically necessary, Imanirad asserts. Instead, monitoring for the occurrence of toxicity is prioritized, and therapeutic strategies such as antibiotics are implemented if skin toxicity manifests, he says. This nuanced approach aligns with the regimen’s distinct profile and highlights the importance of tailoring strategies to the specific toxicities associated with different treatment regimens, Imanirad concludes.