Heterogeneity between subgroups of first-line chemoimmunotherapy for extensive-stage small cell lung cancer patients: a meta-analysis and systematic review

Objectives: Differences in clinicopathological characteristics of extensive-stage small cell lung cancer (ES-SCLC) patients may influence the immune response. This study aims to evaluate the heterogeneity of response to first-line chemoimmunotherapy between subgroups in ES-SCLC to screen out suitable populations.

Materials and methods: We searched the PubMed, EMBASE, and Cochrane Library databases from inception to December 3, 2022 for randomized controlled trials (RCTs) of ES-SCLC chemoimmunotherapy. We also reviewed main conferences from January 1, 2021 to October 1, 2023. A trial-specific hazard ratio (HR) ratio for each subgroup was calculated, and these ratios were then pooled using the deft approach.

Results: A total of 9 RCTs with 4099 patients were finally included. The pooled ratios were 0.92 (95% CI = 0.77 to 1.09) for OS-HRs and 0.79 (95% CI = 0.55 to 1.13) for PFS-HRs in women versus men. The pooled ratios of OS-HRs and PFS-HRs in patients with positive versus negative PD-L1 expression were 1.26 (95% CI = 0.91 to 1.73) and 1.08 (95% CI = 0.77 to 1.52), respectively. The pooled ratios of OS-HRs and PFS-HRs in patients without versus with brain metastasis were 0.77 (95% CI = 0.59 to 1.01) and 0.71 (95% CI = 0.44 to 1.12). No statistically significant differences were also found in terms of subgroups for age, liver metastasis, smoking status, ECOG PS, LDH level, type of platinum salt and race.

Conclusion: Women or patients with negative PD-L1 expression or with LDH ≤ ULN or without brain metastasis tend to benefit more from first-line chemoimmunotherapy in ES-SCLC. More trials are needed to prospectively validate the therapeutic heterogeneity among clinicopathological characteristics.

Systematic review registration: https://inplasy.com/inplasy-2023-3-0064/ identifier, INPLASY202330064.