Small cell lung cancer patients treated with immune checkpoint inhibitor: a systematic literature review of treatment efficacy, safety and quality of life

Background: This systematic literature review examines the current immune checkpoint inhibitors treatment paradigms, treatment gaps and unmet needs for treating SCLC with respect to efficacy, safety, health related quality of life (HRQoL) and cost-effectiveness.

Methods: A search strategy was developed and executed using the National Library of Medicine bibliographic database (PubMed), Cochrane Library, Embase and Google Scholar. Data regarding efficacy, safety, cost-effectiveness and HRQoL were extracted and entered in a data extraction sheet created a priori.

Results: A total of 4961 patients were comprised in all the 12 studies combined. All the studies focus on extensive stage SCLC (ES-SCLC) and not limited stage SCLC (LS-SCLC). All studies used an ICI as the intervention arm and chemotherapy as the control arm. A statistically significant increase in overall survival (OS) and progression free survival (PFS) was observed when ICIs were added to chemotherapy, especially atezolizumab and durvalumab. ICIs in SCLC resulted in immune-related toxicities that have been well-documented in prior immunotherapy trials; their addition to cytotoxic chemotherapy did not worsen chemotherapy-related toxicities. Out of 12 studies, only 3 (25%) included measures to assess the impact of immunotherapy on SCLC patients' HRQoL. Although domain level scores were limited, the addition of ICIs did not seem to worsen symptoms. Two studies conducted a cost-effectiveness analysis of the combination of atezolizumab plus chemotherapy vs. chemotherapy. The addition of atezolizumab to chemotherapy was not found to be cost-effective in either study.

Conclusion: Combining ICIs with chemotherapy enhanced OS and PFS as well as not worsening HRQoL. Among all ICIs, PD-L1 inhibitors showed better effectiveness. Future studies should focus on real-world settings and more clinical trials using ICIs for not only ES-SCLC but also LS-SCLC.