Highlights

  • Median overall survival reached 47.6 months in treatment-naïve BRAF V600E NSCLC patients.
  • Previously treated patients showed a median OS of 22.7 months.
  • Four-year survival rates were 49% for treatment-naïve and 31% for previously treated patients.

Pfizer Inc. (NYSE:PFE) has released updated follow-up results from the Phase 2 PHAROS trial, evaluating the combination of BRAFTOVI® (encorafenib) and MEKTOVI® (binimetinib) for adults with metastatic non-small cell lung cancer (mNSCLC) carrying the BRAF V600E mutation. In treatment-naïve participants, median overall survival (OS) was reported at 47.6 months after a median follow-up of 52.3 months. Among previously treated patients, median OS was 22.7 months following 48.2 months of follow-up.

The four-year OS rates were 49% for treatment-naïve patients and 31% for previously treated patients, according to pre-specified secondary trial endpoints. These findings were presented in an oral session (1849MO) at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany, and simultaneously published in the Journal of Clinical Oncology.

Trial Context and Safety Profile

Lung cancer remains the leading cause of cancer-related deaths worldwide, with NSCLC accounting for 80–85% of cases. BRAF V600E mutations are found in roughly 2% of NSCLC patients. Prior to targeted therapies, outcomes for patients with this mutation were generally poor with standard chemotherapy.

At the time of the updated analysis, the safety profile of BRAFTOVI + MEKTOVI remained consistent with prior observations. The most commonly reported treatment-related adverse events (≥30%) included nausea (52%), diarrhea (44%), fatigue (33%), and vomiting (30%).

Regulatory Background and Study Design

The Phase 2 PHAROS trial (NCT03915951) is an open-label, multicenter, single-arm study assessing BRAFTOVI + MEKTOVI in treatment-naïve and previously treated patients with BRAF V600E-mutant metastatic NSCLC. The combination therapy received FDA approval in October 2023 and European Commission approval in August 2024, based on the trial’s initial objective response rate (ORR) and duration of response results. The ORR was 75% for treatment-naïve patients and 46% for previously treated participants.

Comments from Trial Investigators

"The PHAROS trial results set a new standard for NSCLC patients with the BRAF V600E mutation, with survival outcomes nearing four years—the longest survival we've seen in people with treatment-naïve metastatic NSCLC who harbor a BRAF V600E mutation," said Melissa Johnson, M.D., Director of Lung Cancer Research at Sarah Cannon Research Institute and PHAROS investigator.

Jeff Legos, Chief Oncology Officer at Pfizer, added, "These long-term survival results reinforce Pfizer's unwavering commitment to improving outcomes in lung cancer and underscore the importance of advancing therapies that can provide a sustained impact for patients."