The identification of numerous oncogenic molecular alterations and the development of strategies to target these drivers have made non–small cell lung cancer (NSCLC) a complicated malignancy to manage. “NSCLC is not one disease—it’s a clinical syndrome that can be identified as multiple different diseases,” said Gregory J. Riely, MD, PhD, Attending Physician, and Vice-Chair, Clinical Research, Department of Medicine, Memorial Sloan Kettering Cancer Center. In his presentation at the NCCN 2023 Annual Conference, Dr. Riely, who is also a member of the NCCN Guidelines Panel for NSCLC, described which oncogenic molecular alterations can be targeted, and the efficacy and safety of their corresponding therapeutics according to line of treatment.
“There are multiple molecular targets with agents approved for use in the first-line setting, including EGFR, ALK, ROS1, RET, MET exon 14, and BRAF mutations. Targeted therapies are addressing targets that we’ve not been able to target before, primarily in the second-line setting,” he said, referring to fam-trastuzumab deruxtecan-nxki for ERBB2 (HER2)-mutant tumors, amivantamab-vmjw and mobocertinib for tumors with EGFR exon 20 insertions, and sotorasib and adagrasib for KRAS G12C–mutant metastatic NSCLC.
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, Zhou C , Ramalingam SS , Kim TM Treatment outcomes and safety of mobocertinib in platinum-pretreated patients with EGFR exon 20 insertion-positive metastatic non-small cell lung cancer: a phase 1/2 open-label nonrandomized clinical trial. JAMA Oncol 2021; 7: e214761. 34647988
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, O’Brien M , Paz-Ares L , Marreaud S Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol 2022; 23: 1274– 1286. 36108662