Emerging drugs for small cell lung cancer: a focused review on immune checkpoint inhibitors

ABSTRACT

Introduction

Small cell lung cancer (SCLC) is an aggressive malignancy that accounts for 15% of all lung cancers. It is characterized by initial responsiveness to therapy followed by rapid disease progression that is relatively resistant to further treatment. Recently, the addition of an immune checkpoint inhibitor (ICI) to chemotherapy has improved survival in patients with advanced disease, the first advance in systemic therapy in SCLC in over 30 years.

Areas covered

In this review, we present an overview of SCLC with a focus on the scope of the problem and standard treatment, followed by a critical assessment of scientific rationale for immunotherapy in SCLC and the clinical trials that have been performed with ICIs in SCLC. Finally, we address ongoing hurdles for the development of ICIs in SCLC and potential avenues for further study.

Expert opinion

Despite solid biological rationale, the results of clinical trials of ICIs in SCLC have yielded modest benefits. A small subset of patients does achieve long-term benefit, but further development of ICIs in SCLC will depend on the identification of predictive biomarkers and the design of combination regimens that take advantage of the molecular alterations that drive the immune-avoidance mechanisms and survival of SCLC cells.

KEYWORDS:

• Small cell lung cancer
• immunotherapy
• nivolumab
• pembrolizumab
• atezolizumab
• durvalumab
• ipilimumab

Declaration of interest

GP Kalemkerian receives research grant funding from Merck, Abbvie, Takeda, and Ascentage. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed research grants to their institution from BMS, Merck, Palobiofarma, Genentech and Abbvie and is on the Consulting/Advisory board for AstraZeneca. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.