Chemotherapy plus immunotherapy as first line combination in older patients with extensive stage small cell lung cancer: A systematic review and meta-analysis.

Abstract

Background: Small-cell lung cancer (SCLC) accounts for 10%-15% of all lung cancers. At diagnosis, nearly two thirds of patients with SCLC have extensive stage (ES), with a median overall survival (OS) less than 12 months. The combination of protein-death-1/protein-death-ligand-1 (PD-1/PD-L1) immune checkpoint inhibitors (ICIs) with first-line platinum plus etoposide chemotherapy has changed the therapeutic landscape for ES-SCLC. Older adults represent most of the cancers diagnosed and deaths by age group, with an expected increase over the next decade. In the real-world setting, about 30%-40% of patients with a diagnosis of SCLC are reported to be over 70-years-old at the time of diagnosis. However, this subgroup of patients is underrepresented in clinical trials. Based on this evidence, we performed this systematic review to define the activity of ICIs plus chemotherapy in older patients with previously untreated ES-SCLC.

Methods: This systematic review was carried out in accordance with the statement in the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic search on multiple electronic databases was conducted from inception to the end of April to identify randomized trials that prospectively evaluated chemotherapy ± PD-1/PD-L1 ICIs. When more than one report of the same study was available, the most recent data (with longer follow-up and/or higher number of patients) was considered. The primary endpoint of the study was efficacy, in terms of overall survival, progression-free survival, and disease control rate.

Results: We selected six randomized clinical trials that enrolled 3396 patients in the meta-analysis. In the experimental arm, 670 patients were 65 years of age and older compared to 504 in the control arm. In the subgroup of patients ≥65 years, adding ICIs to chemotherapy led to a significant benefit in OS [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.72-0.90). There was moderate but not-significant heterogenity among the trials (I² = 47%, P = 0.07).

Conclusion: This systematic review found that the combination of chemotherapy plus ICIs improved OS among older patients with ES-SCLC. Biomarker and comprehensive geriatric assessment are needed to improve the identification and selection of patients with cancer that are uniformly defined as older.