Dr Murray on the Safety of Encorafenib/Binimetinib and Dabrafenib/Trametinib in BRAF V600E+ NSCLC

“There is a significant difference in fever or pyrexia that patients experience between dabrafenib/trametinib, and encorafenib/binimetinib. There's more evidence in the dabrafenib/trametinib group. These are usually [some of] the most common adverse effects that we counsel patients on.”

Joseph C. Murray, MD, PhD, an assistant professor of Oncology, co-director of the Lung Cancer Precision Medicine Center of Excellence, and director of the Upper Aerodigestive Cancer Division Immunotherapy Database at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, discussed the safety profiles of encorafenib (Braftovi) plus binimetinib (Mektovi) and dabrafenib (Taflinlar) plus trametinib (Mekinist) for the treatment of patients with BRAF V600E–mutant non–small cell lung cancer (NSCLC).

The differences between the safety profiles of encorafenib/binimetinib and dabrafenib/trametinib are complicated, notably because phase 2 trials evaluated both, which don’t always capture the full scope of real-world adverse effects (AEs) larger studies can provide, Murray began. He explained that the phase 2 BRF113928 (NCT01336634), PHAROS (NCT03915951), and ENCO-BRAF (NCT04526782) studies demonstrated different safety profiles, notably with the PHAROS and ENCO-BRAF studies showing significant differences in fever or pyrexia experienced between patients receiving encorafenib/binimetinib vs those treated withdabrafenib/trametinib in BRF113928.

Increased signals of gastrointestinal AEs were also prevalent among patients on the PHAROS and ENCO-BRAF studies, specifically including nausea and diarrhea, Murray added. However, some of the more unique AEs were demonstrated in patients who were treated with encorafenib/binimetinib, which showed occurrences of blurred vision, he noted. Other common AEs observed in patients treated with encorafenib/binimetinib included fatigue and cytopenias, Murray said.

Although these safety data are from studies with smaller patient populations, he emphasized that these AEs should still be carefully considered. In clinical practice, Murray focuses on areas that could affect dose reductions, interruptions, and permanent discontinuations. In reviews comparing dose reductions, interruptions, and discontinuations, there has been an overall decrease, particularly in patients treated with encorafenib/binimetinib, Murray explained. He concluded that seeing this comparison determined potential tolerability of the regimen and could reduce the chance of permanent treatment discontinuation.