Dr. Reckamp on Targeted Therapy Options for Rare Mutations in NSCLC

Karen L. Reckamp, MD, MS, director of medical oncology, medical oncology director of the Women’s Guild Lung Institute, associate director for clinical research, Cedars-Sinai Cancer, discusses targeted therapy options for rare mutations in non—small cell lung cancer (NSCLC).

BRAF mutations are the most prominent rare mutations in NSCLC, says Reckamp. They are common in patients with a history of smoking, she adds.

In June 2017, the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) gained FDA approval for the treatment of patients with metastatic NSCLC whose tumors express the BRAF V600E mutation. The approval was based on findings from a single-arm, phase II trial (NCT01336634) that demonstrated a 2-year overall survival rate of 51% with the combination.

Less than 1% of patients with NSCLC harbor an NTRK fusion, says Reckamp. Though it is an exceedingly rare mutation, larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) were granted accelerated approval in 2018 and 2019, respectively, for the treatment of patients with NTRK-positive solid tumors. The indications are specific to patients who have a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed on therapy or have no alternative treatments.

Performing comprehensive genomic testing is critical to identifying these rare aberrations, concludes Reckamp.