Efficacy and safety of first-line PD-L1/PD-1 inhibitors in limited-stage small cell lung cancer: a multicenter propensity score matched retrospective study

Jingyuan Xie; Ke Xu; Zijing Cai; Mo Chen; Yuxin Jiang; Jinjun Ye; Xinqing Lin; Tangfeng Lv; Ping Zhan

doi:10.21037/tlcr-24-24

Efficacy and safety of first-line PD-L1/PD-1 inhibitors in limited-stage small cell lung cancer: a multicenter propensity score matched retrospective study

Transl Lung Cancer Res. 2024 Mar 29;13(3):526-539. doi: 10.21037/tlcr-24-24. Epub 2024 Mar 27.

Authors

Jingyuan Xie^#^{1

2}, Ke Xu^#², Zijing Cai^#³, Mo Chen³, Yuxin Jiang⁴, Jinjun Ye⁵, Xinqing Lin⁶, Tangfeng Lv^{2

3}, Ping Zhan^{2

3}

Affiliations

¹ Department of Respiratory and Critical Care Medicine, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, China.
² Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, China.
³ Department of Respiratory and Critical Care Medicine, Jinling Hospital, Jinling Clinical College of Nanjing Medical University, Nanjing, China.
⁴ Department of Respiratory and Critical Care Medicine, Jinling Hospital, School of Medicine, Southeast University, Nanjing, China.
⁵ Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China.
⁶ State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

^# Contributed equally.

Abstract

Background: The prognosis of small cell lung cancer (SCLC) patients is poor, and the standard first-line treatment for limited-stage small cell lung cancer (LS-SCLC) is still chemotherapy and thoracic radiotherapy. The primary objectives of our study were to confirm the superior efficacy of first-line immune checkpoint inhibitors (ICIs) plus etoposide and platinum (EP) for LS-SCLC and find crucial biomarkers.

Methods: We analyzed LS-SCLC patients from three medical centers, employing propensity score matching for group comparability. Survival outcomes were estimated by Kaplan-Meier and Cox regression analyses. Additionally, we conducted univariate and multivariate analyses to investigate potential predictive factors.

Results: Among 150 patients in our study, we successfully matched 41 pairs. The median overall survival (OS) was 29.5 months in the EP + ICIs group and 20.0 months in the EP group {hazard ratio (HR) =0.64 [95% confidence interval (CI): 0.41-1.02], P=0.059}. The median progression-free survival (PFS) was significantly extended in the EP + ICIs group (14.6 months), compared to the EP group (8.6 months) [HR =0.42 (95% CI: 0.28-0.63), P<0.001]. After matching, patients receiving chemo-immunotherapy had a median OS of 36.1 months, significantly surpassing those receiving chemotherapy alone (19.0 months) [HR =0.51 (95% CI: 0.28-0.93), P=0.02]. And the patients in the EP + ICIs group also had longer PFS after matching [HR =0.42 (95% CI: 0.25-0.71), P=0.001]. No significant difference in the objective response rate (ORR) and treatment-related adverse events (trAEs) between the two groups was found (ORR: EP: 81.0%, EP + ICIs: 90.0%, P=0.14; trAEs: EP: grade 1-2, 49.3%; grade 3-4, 42.5%; EP + ICIs: grade 1-2, 40.0%; grade 3-4, 49.1%, P=0.62). The multivariate analysis presented that the history of immunotherapy [EP + PD-1 inhibitors: HR =0.33 (95% CI: 0.17-0.62), P=0.001; EP + PD-L1 inhibitors: HR =0.18 (95% CI: 0.06-0.60), P=0.005] and baseline lung immune prognostic index (LIPI) [intermediate: HR =2.22 (95% CI: 1.20-4.13), P=0.01; poor: HR =2.03 (95% CI: 0.71-5.77), P=0.18] were independent prognostic factors for PFS among all LS-SCLC cases. However, no independent prognostic factor was identified for OS.

Conclusions: Our real-world data showed promising clinical efficacy and tolerable safety of first-line programmed cell death protein 1 (PD-1) inhibitors or programmed cell death ligand 1 (PD-L1) inhibitors in cases with LS-SCLC. Additionally, LIPI may serve as a valuable prognostic factor.

Keywords: Limited-stage small cell lung cancer (LS-SCLC); lung immune prognostic index (LIPI); programmed cell death ligand 1 inhibitors (PD-L1 inhibitors); programmed cell death protein 1 inhibitors (PD-1 inhibitors).