Combined Therapies for Small-Cell Lung Cancer


Small cell lung cancer is a rapidly progressive
cancer with a median survival of approximately 10 months after first line treatment with
platinum-based chemotherapy and etoposide. The tumor has a high mutation rate suggesting
potential susceptibility to immune checkpoint inhibitors. Atezolizumab is a humanized monoclonal IgG
antibody that binds to PD-L1 on tumor cells and blocks binding to PD-1 allowing T cells
to respond to and kill tumor cells. This study was a randomized, double
blind, placebo-controlled phase 3 trial that evaluated adding atezolizumab to first line chemotherapy
in patients with extensive stage small cell lung cancer. The co-primary endpoints were overall survival
and progression-free survival. 403 patients were randomized to receive 4
cycles of carboplatin and etoposide with either 1200 mg of atezolizumab or placebo. After a median follow up of 13.9 months, those
randomized to atezolizumab had a significantly longer median overall survival (12.3 months)
than those assigned to placebo (10.3 months). Progression-free survival was also improved
in the atezolizuzumab group with a median of 5.2 months as compared with 4.3 months in the
placebo group. Grade 3 or 4 treatment-related adverse events
occurred in most patients in both groups and commonly included anemia and neutropenia. Immune -related adverse events were reported
in 39.9% of patients receiving atezolizumab and 24.5% of patients receiving placebo. The authors conclude that in patients with
extensive stage small cell lung cancer, overall survival and progression-free survival were improved
by adding atezolizumab to chemotherapy. Full trial results are available at NEJM.org.