In a retrospective cohort study (FRONT-BRAF) reported in The Lancet Oncology, Di Federico et al found that first-line PD-1 or PD-L1 inhibitors with or without platinum-based chemotherapy were associated with improved overall survival compared with BRAF and MEK inhibitors in patients with metastatic BRAF V600E–mutated non–small cell lung cancer (NSCLC).
Study Details
The study included 284 patients from sites in the United States, Italy, France, and Brazil who started first-line treatment between January 2015 and July 2024. Of these, 88 (31%) received PD-1 or PD-L1 inhibitors with or without chemotherapy and 196 received BRAF and MEK inhibitors consisting of dabrafenib and trametinib or encorafenib and binimetinib. Patients in the PD-1/PD-L1 inhibitor with or without chemotherapy group were more likely to have a history of smoking (83% vs 60%) and higher PD-L1 expression (eg, ≥ 50% in 66% vs 39%). The primary endpoint was overall survival with first-line PD-1/PD-L1 inhibitors with or without chemotherapy vs BRAF and MEK inhibitors.
Key Findings
Median follow-up was 45.0 months (95% confidence interval [CI] = 39.0–55.7 months). In adjusted analysis, median overall survival was 40.9 months (95% CI = 33.3 months to not reached) in the PD-1/PD-L1 inhibitor with/without chemotherapy group vs 25.2 months (95% CI = 19.9–31.1 months) in the BRAF/MEK inhibitors group (hazard ratio [HR] = 0.69, 95% CI = 0.49–0.98, P = .039).
In subgroup analyses, the PD-1/PD-L1 inhibitor with/without chemotherapy group had significantly longer median overall survival in patients with a history of smoking (HR = 0.60, P = .013), those with a PD-L1 tumor proportion score of ≥ 1% (HR = 0.66, P = .039), those aged 70 years or older (HR = 0.54, P = .029), those with TP53 comutations (HR = 0.46, P = .0048), and those without brain metastases (HR = 0.66, P = .045).
The investigators concluded: “First-line [immune checkpoint inhibitors] with or without chemotherapy were associated with improved overall survival compared with BRAF and MEK inhibitors in participants with metastatic BRAF V600E–mutated NSCLC, particularly among specific subpopulations. These findings, although suggesting potential clinical relevance, remain exploratory and require confirmation from prospective studies.”
Biagio Ricciuti, MD, of Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by NextGenerationEU. For full disclosures of all study authors, visit thelancet.com.
