OBJECTIVES: Despite the initial sensitivity of SCLC to first-line chemotherapy, relapse almost always occurs. There is currently no established treatment beyond second-line therapy; only a few patients receive third-line therapy. To better understand the unmet clinical need of relapsed SCLC, we conducted an SLR of clinical trials that evaluated the efficacy and safety of 3L+ SCLC treatments.

METHODS: Following methodological guidance of the Centre for Reviews and Dissemination and PRISMA, databases (MEDLINE, Embase, and Cochrane Library) were searched for journal articles published from 1986 to April 2022 and were supplemented by hand searching of conference abstracts (2018 to April 2022). Two independent reviewers conducted screening, with data abstraction conducted by one reviewer and validated by a second. Quality assessment was performed using standardised tools. Efficacy data (overall survival (OS), progression-free survival (PFS), objective response rate (ORR)) and grade ≥3 treatment-related adverse events (TRAE) were summarised.

RESULTS: Database searches returned 9,988 records, of which 18 records (reporting on 14 unique trials) met the final inclusion criteria. Most trials reported on Asian populations (n=8). All but one trial were based on a single-arm study design with small patient populations (only 3 trials included >100 3L+ patients). Overall, 12 monotherapies and 4 combination therapies were evaluated, none of which are recommended by the European Society for Medical Oncology treatment guidelines for recurrent SCLC. Across all treatments, median OS ranged from 5.0 to 7.7 months, and median PFS from 1.2 to 4.1 months. ORR ranged from 4.5% to 20.8%. No therapy was clearly associated with improved clinical outcomes. Grade ≥3 TRAE were observed in 9.6% to 52% of patients.

CONCLUSIONS: Therapies in 3L+ SCLC clinical trials demonstrated limited efficacy with a propensity for a TRAE, leaving patients with a dismal prognosis. No RCT was identified in this SLR that establishes a standard of care treatment for 3L+ SCLC.