Efficacy Outcomes from PHAROS

This segment focuses on the efficacy results from the PHAROS phase II study, highlighting clear differences between treatment-naïve and previously treated patients with BRAF V600E-mutant NSCLC. Among the 59 treatment-naïve patients, outcomes were notably strong: an objective response rate of 75%, a median PFS of approximately 30 months, and a median OS of nearly 4 years (47.6 months). These results compare favorably with historical data in this population, although the speakers emphasize caution given the lack of head-to-head comparisons with other BRAF-MEK combinations such as dabrafenib and trametinib.

In contrast, patients who had received one prior line of therapy showed more modest outcomes, with a 49% response rate, median PFS of about 9 months, and median OS of 22.7 months. This discrepancy was not attributed to prior BRAF-targeted therapy, but rather reflects a broader pattern seen across oncology: patients with more extensive prior treatment histories often derive less benefit from subsequent therapies.

The pronounced efficacy advantage in the treatment-naïve group strongly supports the use of BRAF-directed therapy in the frontline setting. Combined with emerging safety improvements, these data shift the clinical debate toward starting with targeted therapy rather than reserving it for later lines, particularly given the risk that some patients may never reach second-line treatment.