Dana-Farber Study Suggests Immunotherapy May Be a Better First Treatment for a Subset of Non-Small Cell Lung Cancer Patients

Research Summary

Study Title: First-Line Immunotherapy Versus BRAF/MEK Targeted Therapy in Advanced BRAFV600E-Mutated Non-Small Cell Lung Cancer: An International Multicenter Cohort Study

Publication: The Lancet Oncology

Corresponding Dana-Farber Cancer Institute authors: Dr. Biagio Ricciuti

Summary: An international, multi-center study found that patients with advanced non-small cell lung cancer (NSCLC) whose tumors carry a rare change in the BRAF gene, called BRAFV600E, lived longer when they received immunotherapy as their first treatment, with or without chemotherapy, compared with those who first received targeted drugs known as BRAF/MEK inhibitors.

The study looked back at patients treated at cancer centers in several countries and compared two common first treatment options: immunotherapy-based treatment versus BRAF/MEK targeted therapy. Patients who started with immunotherapy lived a median of 41 months, compared with 25 months for those who started with BRAF/MEK inhibitors. The benefit from immunotherapy was especially clear in patients whose tumors had PD-L1 levels of 1% or higher, in people with a history of smoking, and in patients who did not have cancer that had spread to the brain. Although targeted therapy led to more frequent and often faster tumor shrinkage, patients treated first with immunotherapy tended to have better long-term outcomes. The study also found that patients whose tumors had an additional TP53 mutation did much worse on BRAF/MEK inhibitors but not on immunotherapy, suggesting that the broader genetic makeup of the tumor should be considered when choosing treatment. Finally, the researchers showed that it was safe to give BRAF/MEK inhibitors after immunotherapy, easing earlier concerns about side effects when using these treatments one after the other.

Significance: Patients with BRAFV600E-mutated NSCLC have often been treated by following approaches used for other gene-driven lung cancers, where targeted therapies are usually given first. These new findings suggest that this may not be the best strategy for many people with BRAFV600E mutations. The results support using immunotherapy-based treatment as a first option for many patients, particularly those with PD-L1–positive tumors, a smoking history, and no brain metastases. More research, including prospective, randomized clinical trials, is needed to confirm these results, determine the best order in which to give immunotherapy and targeted therapy, and discover additional markers that can help match each patient to the most effective treatment.

Funding: NextGenerationUE.