Baseline PD-L1 expression on circulating immune cells as a predictor of survival and immune-related adverse events in extensive-stage small-cell lung cancer patients treated with durvalumab and carboplatin-etoposide (NCT04712903 Trial).

INTRODUCTION

Despite improved efficacy with first-line immune checkpoint inhibitors plus platinum-based chemotherapy for extensive-stage small cell lung cancer (ES-SCLC), long-term survival remains limited. There is currently no available predictive biomarker to identify which patients would benefit most from this treatment. We hypothesized that pre-treatment PD-L1 expression on circulating immune cells might predict survival outcomes and toxicity. MATERIAL AND

METHODS

This prospective, multi-center observational study included patients with untreated ES-SCLC treated with first-line durvalumab plus platinum-based chemotherapy. The percentages of circulating PD-L1+ immune cells at baseline were analysed by flow cytometry to assess their association with survival outcomes and the development of immune-related adverse events (irAEs).

RESULTS

Among 41 patients with ES-SCLC, 65.9% were male, 73.2% had an ECOG-PS 1, 9.8% had central nervous system (CNS) metastases and 31.7% had liver metastases. Sixteen patients (39%) experienced irAEs. Median PFS was longer in patients with high percentages of circulating PD-L1+ monocytes compared to those with low percentages: 8.97 months (95% CI NR to NR) vs. 5.97 months (95% CI 4.65 to 7.28), p = 0.007. There was a trend toward longer median OS in patients with ES-SCLC and high percentages of circulating PD-L1+ monocytes versus low percentages: NR (95% CI NR-NR) vs. 9.13 months (95% CI 6.34 to 11.92), p = 0.092. Patients with higher circulating PD-L1+ neutrophils correlated with the development of irAES (p = 0.007).

CONCLUSIONS

Our results showed a statistically significant longer PFS in patients with ES-SCLC and high percentages of circulating PD-L1+ monocytes. This suggests PD-L1 expression on monocytes might be established as a predictive biomarker for patients with ES-SCLC treated with upfront chemo-immunotherapy. TRIAL REGISTRATION: NCT04712903 Trial. Last registered 1 December 2025, https://www.clinicaltrials.gov/study/NCT04712903 .