Immune Checkpoint Inhibitors in Small Cell Lung Cancer: A Partially Realized Potential

Abstract

Small cell lung cancer (SCLC) is a highly lethal subtype of lung cancer that has seen few therapeutic advances, despite ongoing concerted efforts. Immunotherapy has been an effective option in other carcinogen-related cancers and has shown modest activity in SCLC. Monotherapy with the anti-PD-1 antibody nivolumab in patients with at least two prior lines of therapy was associated with a response rate of 11.9% and a median duration of response of 17.9 months, leading to accelerated approval by the Food and Drug Administration (FDA) as third-line therapy for SCLC. Second-line checkpoint inhibitors have not performed well enough to change the standard of care, and maintenance immunotherapy has not shown significant benefit. However, the incorporation of concurrent immunotherapy in the first-line treatment of SCLC has improved outcomes. The addition of the anti-PD-L1 antibody atezolizumab to standard carboplatin plus etoposide led to an improvement in progression free survival (PFS) and overall survival, the first such improvement in over 30 years leading to the approval of atezolizumab as part of first-line therapy for advanced SCLC. While these landmark approvals offer promising novel treatment options for this recalcitrant disease, more work is needed to optimize their delivery and to build upon these important advances.

Keywords: Atezolizumab; Checkpoint inhibitors; Immunotherapy; Nivolumab; SCLC.