Perioperative Nivolumab in Resectable Lung Cancer.

BACKGROUND: Standard treatment with neoadjuvant nivolumab plus chemotherapy significantly improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative treatment (i.e., neoadjuvant therapy followed by surgery and adjuvant therapy) with nivolumab may further improve clinical outcomes. METHODS: In this phase 3, randomized, double-blind trial, we assigned adults with resectable stage IIA to IIIB NSCLC to receive neoadjuvant nivolumab plus chemotherapy or neoadjuvant chemotherapy plus placebo every 3 weeks for 4 cycles, followed by surgery and adjuvant nivolumab or placebo every 4 weeks for 1 year. The primary outcome was event-free survival according to blinded independent review. Secondary outcomes were pathological complete response and major pathological response according to blinded independent review, overall survival, and safety. RESULTS: At this prespecified interim analysis (median follow-up, 25.4 months), the percentage of patients with 18-month event-free survival was 70.2% in the nivolumab group and 50.0% in the chemotherapy group (hazard ratio for disease progression or recurrence, abandoned surgery, or death, 0.58; 97.36% confidence interval [CI], 0.42 to 0.81; P<0.001). A pathological complete response occurred in 25.3% of the patients in the nivolumab group and in 4.7% of those in the chemotherapy group (odds ratio, 6.64; 95% CI, 3.40 to 12.97); a major pathological response occurred in 35.4% and 12.1%, respectively (odds ratio, 4.01; 95% CI, 2.48 to 6.49). Grade 3 or 4 treatment-related adverse events occurred in 32.5% of the patients in the nivolumab group and in 25.2% of those in the chemotherapy group. CONCLUSIONS: Perioperative treatment with nivolumab resulted in significantly longer event-free survival than chemotherapy in patients with resectable NSCLC. No new safety signals were observed. (Funded by Bristol Myers Squibb; CheckMate 77T ClinicalTrials.gov number, NCT04025879.).

Novel therapeutic targets in non-small cell lung cancer.

The development of personalized medicine with a focus on novel targeted therapies has supplanted the one-size-fits-all approach to the treatment of many cancers, including non-small cell lung cancer. Targeted therapies, if given to a patient subpopulation enriched by the presence of relevant molecular targets, can often abrogate cell signaling that perpetuates cancer progression. Critical targets activating procancer pathways include, but are not limited to, epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (MET), vascular endothelial growth factor (VEGF), VEGF receptor, GTPase KRAS (KRAS), receptor tyrosine protein kinase erbB-2 (HER2), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA), serine/threonine-protein kinase B-raf (BRAF), and insulin-like growth factor 1 receptor (IGF-1R). Some target-directed therapies, such as epidermal growth factor receptor tyrosine kinase inhibitors and anti-VEGF monoclonal antibody, have already been approved for clinical use. Others, such as those targeted to MET, VEGFR, HER2, PIK3CA, and IGF-1R, are in clinical testing. This review describes molecular targets in non-small cell lung cancer that are in development or being clinically applied and their implications for developing novel anticancer therapies for this previously refractory malignancy.