Advances in Treatment of Recurrent Small Cell Lung Cancer (SCLC): Insights for Optimizing Patient Outcomes from an Expert Roundtable Discussion

Abstract

Second-line treatment options for patients with relapsed, extensive-stage small cell lung cancer (ES-SCLC) are limited, and even with currently available treatments, prognosis remains poor. Until recently, topotecan (a topoisomerase I inhibitor) was the only drug approved by the United States (US) Food and Drug Administration (FDA) for the management of ES-SCLC following progression after first-line treatment with etoposide plus a platinum derivative (EP; carboplatin preferred). With the most recent approval of EP plus a programmed death ligand 1 (PD-L1) inhibitor, there are now more therapeutic options for managing ES-SCLC. A number of novel agents have emerging data for activity in relapsed ES-SCLC, and single-agent lurbinectedin (an alkylating drug and selective inhibitor of oncogenic transcription and DNA repair machinery in tumor cells) has conditional FDA approval for use in this patient population. Trilaciclib, a short-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor, has also been recently approved as a supportive intervention for use prior to an EP or a topotecan-containing regimen to diminish the incidence of chemotherapy-induced myelosuppression. The current review is based on a recent expert roundtable discussion and summarizes current therapeutic agents and emerging data on newer agents and biomarkers. It also provides evidence-based clinical considerations and a treatment decision tool for oncologists treating patients with relapsed ES-SCLC. This paper discusses the importance of various factors to consider when selecting a second-line treatment option, including prior first-line treatment, available second-line treatment options, tumor platinum sensitivity, and patient characteristics (such as performance status, comorbidities, and patient-expressed and perceived values).

Keywords: Atezolizumab; Biomarkers; Durvalumab; Etoposide/platinum; Extensive-stage; Immunotherapy; Lurbinectedin; Relapsed; Small cell lung cancer; Topotecan.

Fig. 1

A practical management guide for ES-SCLC. ^aEP + immunotherapy is the preferred first-line standard of care for all patients with extensive-stage-small-cell lung cancer (ES-SCLC). In the case of a patient who previously received EP alone and remains platinum sensitive, EP rechallenge with immunotherapy may be considered. ^bPlatinum-sensitive is defined as either chemotherapy naive or relapse > 90 days after cessation of prior chemotherapy and platinum-resistant as relapse ≤ 90 days after prior chemotherapy. ^cTopotecan and irinotecan remain possible second-line options