Chemo-immunotherapy as first-line treatment for small-cell lung cancer

Abstract

Small-cell lung cancer (SCLC) is a highly lethal subtype of lung cancer. Despite concerted efforts over the past several decades, there have been limited therapeutic advances. Traditional chemotherapy offers a high response rate and rapid symptomatic improvement, but its benefit is fleeting, and relapse is quick and unforgiving. Immunotherapy has delivered improved outcomes for patients with many cancers and there was compelling rationale for development in SCLC. While initial efforts with cytotoxic T-lymphocyte protein-4 inhibitors failed to improve upon chemotherapy alone, the addition of programmed death ligand-1 (PD-L1) inhibitors to first-line chemotherapy finally provided long-awaited gains in survival. Atezolizumab, when added to carboplatin and etoposide, improved both progression-free survival and overall survival. Durvalumab, when added to platinum plus etoposide, similarly improved OS. Biomarker development has stalled as PD-L1 expression and tumor mutational burden have not been useful predictive biomarkers. However, based on the significant survival improvements, both atezolizumab and durvalumab were approved by the US Food and Drug Administration to be given with first-line chemotherapy, and these regimens represent the new standards of care for SCLC.