Immunotherapy in Small-Cell Lung Cancer: Biomarker Strategies Remain Elusive
This review covers the clinical development of immune checkpoint inhibitors in small-cell lung cancer, where atezolizumab plus chemotherapy has achieved the first overall survival improvement in three decades. However, PD-L1 expression is typically low or absent in SCLC, precluding its use as a predictive biomarker, and blood-based tumour mutational burden has also failed to predict benefit. The lack of validated biomarkers to select patients remains the central challenge for labs supporting SCLC immunotherapy decisions.
The original study
Immunotherapeutic approaches for small-cell lung cancer.
- Authors
- Iams WT, Porter J, Horn L
- Journal
- Nature reviews. Clinical oncology
- Type
- Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review
- PMID
- 32055013
Original abstract
Immune-checkpoint inhibitors (ICIs) are approved in the first-line and third-line settings for patients with extensive-stage or relapsed small-cell lung cancer (SCLC), respectively. In the first-line setting, the addition of the anti-programmed cell death 1 ligand 1 (PD-L1) antibody atezolizumab to chemotherapy improves overall survival (OS). In patients with relapsed disease, data from nonrandomized trials have revealed promising responses, although a significant improvement in OS over that obtained with conventional chemotherapy was not achieved in a randomized trial in this setting. Substantial research interest exists in identifying predictive biomarkers that could guide the use of ICIs in patients with SCLC. PD-L1 expression is typically low or absent in SCLC, which has precluded its use as a predictive biomarker. Tumour mutational burden might have some predictive value, although blood-based measures of tumour mutational burden did not have predictive value in patients receiving atezolizumab plus chemotherapy in the first-line setting. After three decades, ICIs have finally enabled an improvement in OS for patients with SCLC; however, a substantial amount of research remains to be done, including identifying the optimal therapeutic strategy and predictive biomarkers. In this Review, we describe the available data on clinical efficacy, the emerging evidence regarding biomarkers and ongoing clinical trials using ICIs and other immunotherapies in patients with SCLC.