Is Immune Checkpoint Inhibition of Benefit in BRAF-Positive NSCLC?

By: Julia Cipriano, MS
Posted: Thursday, August 15, 2024

Both patients with locally advanced and advanced BRAF-positive non–small cell lung cancer (NSCLC) appear to benefit from immunotherapy-based treatment, according to Mariano Provencio, MD, PhD, of Hospital Puerta de Hierro, Madrid, and colleagues. Their findings, which were published in the journal Lung Cancer, suggest a potential avenue for the management of these small populations.

“[Prior to this study,] the efficacy of immune checkpoint inhibitors in patients with NSCLC and BRAF mutations remained uncertain,” the investigators commented. “The extraordinary outcomes observed in [those with resectable stage IIIA/B disease who underwent] chemoimmunotherapy, including a 100% pathologic complete response rate, further reinforce the therapeutic merit of the neoadjuvant chemoimmunotherapy approach in patients with NSCLC.”

Plasma and tissue samples from patients with resectable stage IIIA/B and stage IV NSCLC from the NADIM and NADIM II clinical trials (NADIM cohort; n = 116) and a prospective academic cohort (n = 84), respectively, were analyzed via next-generation sequencing. The investigators identified oncogenic BRAF mutations in four samples from the NADIM cohort (all treated with neoadjuvant chemoimmunotherapy) and four samples from the academic cohort (first-line, immunotherapy: n = 2; chemoimmunotherapy: n = 2). At data cutoff, the entire BRAF-mutated population was alive without evidence of disease.

Patients with BRAF–wild-type tumors from the academic cohort conversely demonstrated a median progression-free survival of 5.5 months (log-rank P = .013) and a median overall survival of 12.0 months (log-rank P = .046). Likewise, the 36-month progression-free and overall survival probabilities were 60.5% and 76.1%, respectively, for those from the NADIM cohort. The pathologic complete response rate was found to be higher in patients with BRAF-positive vs BRAF–wild-type tumors who underwent neoadjuvant chemoimmunotherapy (100% vs 44.3%; relative risk ratio = 2.26; P < .001).

Disclosure: For full disclosures of the study authors, visit lungcancerjournal.info.

Lung Cancer