Selecting Initial Therapy in NSCLC: First Step Is Histology
Posted: Monday, September 28, 2020
In the treatment of patients with non–small cell lung cancer (NSCLC), understanding tumor histology is critical to optimal biomarker evaluation and selection of initial therapy, according to Gregory J. Riely, MD, PhD, Vice Chair of Clinical Research, Memorial Sloan Kettering Cancer Center, New York. A key component of biomarker evaluation centers on the assessment of PD-L1 status, as well as testing for actionable oncogenic drivers such as EGFR, ALK, ROS1, BRAF, MET exon 14, RET, and NTRK. Dr. Riely explored the sequencing of therapy for patients with NSCLC in his presentation during the NCCN 2020 Virtual Annual Conference, highlights of which were published in JNCCN–Journal of the National Comprehensive Cancer Network.
“The way PD-L1 testing is done is a bit of a moving target right now,” commented Dr. Riely, “but I would emphasize that it has to be performed for all patients with NSCLC.”
Dr. Riely explained that patients will be led down one of three treatment paths based on histologic assessment findings, molecular analysis, and PD-L1 testing. For about 25% of patients, gene mutations, or rearrangements will guide choices in targeted therapies. For approximately 45% of patients, low or no PD-L1 expression will be found; for these patients without an oncogenic driver, the preferred initial treatment is pembrolizumab in combination with chemotherapy, he noted. And for the remaining 30% of patients who have high PD-L1 expression (at least 50%), pembrolizumab monotherapy is indicated.
More specifically, Dr. Riely reviewed the preferred first-line therapeutic options based on the target gene mutation or rearrangement: selpercatinib for RET fusion; osimertinib for EGFR mutation; alectinib for ALK fusions; crizotinib or entrectinib for ROS1 mutation; the combination of dabrafenib and trametinib for BRAF V600; capmatinib for MET exon 14; and larotrectinib or entrectinib for NTRK fusions.
Disclosure: Dr. Riely has received grant/research support from Merck, Novartis, Mirati Therapeutics, Pfizer, Roche, and Takeda.