Introduction to the PHAROS (FAROS) Trial and Study Design

Segment II discusses the PHAROS/FAROS trial, the foundational evidence supporting encorafenib + binimetinib in metastatic BRAF V600E NSCLC. Dr. Rotow provides an overview of the study’s structure, noting its single-arm, two-cohort design that enrolled both treatment-naïve and previously treated patients. Although the study lacks a randomized comparator arm, she explains that such designs are common and often necessary in rare molecular subsets where randomized trials are impractical.

The hosts detail key eligibility criteria, including confirmed BRAF V600E mutation and metastatic disease. They emphasize the importance of understanding patient characteristics, noting that participants tended to be older, with typical comorbidities seen in real-world NSCLC populations. This reinforces the need to interpret efficacy and safety outcomes in a clinically meaningful context.

A central element of this segment is the discussion of encorafenib and binimetinib’s mechanism of action. Encorafenib is a potent BRAF inhibitor with favorable pharmacologic properties, and binimetinib complements it by targeting downstream MEK signaling. Together, the dual blockade is intended to enhance tumor control while reducing MAPK pathway reactivation, a common resistance mechanism.

The speakers also begin previewing the promising survival outcomes, noting the unusually long follow-up period in PHAROS, which enables meaningful assessment of progression-free and overall survival. This long-term perspective is significant, as earlier BRAF/MEK trials often had more limited follow-up and smaller patient numbers.

Finally, they acknowledge that although the trial was not randomized, it nonetheless delivers critical insights that heavily influence modern treatment decision-making. For rare oncogenic subsets like BRAF V600E, such data often become the de-facto standard for clinical practice.