Early Checkpoint Inhibition With Cytotoxic Chemotherapy Improves OS, PFS in Extensive-Stage SCLC

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Researchers evaluated the combined effect of chemotherapy and atezolizumab in treating extensive-stage SCLC.
Researchers evaluated the combined effect of chemotherapy and atezolizumab in treating extensive-stage SCLC.

A combination of checkpoint inhibition with cytotoxic chemotherapy as a first-line treatment for extensive-stage small cell lung cancer (SCLC) resulted in increased overall survival (OS) and progression-free survival (PFS) compared with chemotherapy alone, a study published in the New England Journal of Medicine has shown.

Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1) signaling was previously shown to be a promising treatment for extensive-stage small cell lung cancer. In this study, researchers evaluated the combined effect of chemotherapy and atezolizumab, a drug that inhibits PD-L1 signaling and restores tumor-specific T cell immunity, in treating extensive-stage small cell lung cancer.

The study was a double-blind, placebo-controlled, phase 3 trial. Patients with extensive-stage small cell lung cancer who had not previously been treated were randomly assigned into 2 groups. A total of 201 patients received carboplatin and etoposide with atezolizumab, and 202 patients received carboplatin and etoposide with a placebo, for four 21-day cycles, followed by a maintenance phase in which they received only atezolizumab or the placebo. The maintenance phase continued until unacceptable toxic effects were observed, disease progression was noted, or no additional clinical benefit was determined.

The median overall survival at the 13.9 month follow-up for the atezolizumab group was 12.3 months, compared with 10.3 months in the placebo group. Progression-free survival for the atezolizumab group was 5.2 months vs 4.3 months for the placebo group. “This suggests that combining checkpoint inhibition with cytotoxic therapy during induction may be beneficial and potentially necessary to improve overall survival beyond that seen with the current standard of care and thus it may be a preferred treatment approach over maintenance checkpoint-inhibitor therapy alone.” concluded the authors. “Further studies directly comparing the 2 treatment approaches are needed.”

Reference

Horn L, Mansfield AS, Szczęsna A, et. al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer [published online September 25, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1809064

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