Clinical impact of first-line chemotherapy combined with immune checkpoint inhibitors for limited-stage small cell lung cancer patients: a real-world propensity score matching study

Abstract

Background: Findings from the ADRIATIC clinical trial revealed that adjuvant treatment with durvalumab following chemoradiotherapy (CRT) in limited-stage small cell lung cancer (LS-SCLC) significantly improved both overall survival (OS) and progression-free survival (PFS). However, the clinical impact remains uncertain in real-world clinical practice.

Materials and methods: We gathered data of LS-SCLC patients at the First Affiliated Hospital of Zhengzhou University and conducted propensity score-matched analysis (PSM), Kaplan-Meier (K-M) method and Cox proportional hazards regression.

Results: Prior to PSM, survival results demonstrated the mOS of the chemotherapy group was 20.34 months (95% confidence interval (CI): 18.80 - 23.57 months), whereas that of the chemotherapy + ICIs group was 26.38 months (95% CI: 22.97 - 38.90 months); the hazard ratio (HR) was 0.603 (95% CI: 0.413 - 0.880, P = 0.008, sample size: 102 vs 66). Simultaneously, the mPFS of the chemotherapy + ICIs group was also greater than that of the chemotherapy group, being 10.37 months (95% CI: 9.03 - 12.90 months) and 7.87 months (6.63 - 9.73 months), HR = 0.651 (95% CI: 0.457 - 0.927). After 1:1 matching for basic variables in the chemotherapy group (sample size: 66), its mOS was at 20.22 months, and mPFS was longer at 8.50 months. The multivariate analysis presented that radiotherapy, systemic immune-inflammation index (SII) > 666.29, and platelet-to-lymphocyte ratio (PLR) > 261.39 were independent prognostic factors for OS.

Conclusion: These results offer reliable references for clinicians when formulating treatment strategies for LS-SCLC patients and also provide support for future clinical trials.

Keywords: Cox proportional hazards; ICIs; LS-SCLC; PSM; chemotherapy; prognostic.

Figure 1

Diagram of the patient’s selection process. LS-SCLC, limited-stage small cell lung cancer; ICIs, immune checkpoint inhibitors.

Figure 2

Survival outcomes of chemotherapy/chemotherapy +ICIs. (A) K-M curves of OS stratified by chemotherapy/chemotherapy +ICIs; (B) K-M curves of PFS stratified by chemotherapy/chemotherapy +ICIs; (C) Forest plot of subgroup analysis of OS; (D) Forest plot of subgroup analysis of PFS; OS, overall survival; PFS, progression free survival; ICIs, immune checkpoint inhibitors. HR, hazard ratio; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; PCI prophylactic cranial irradiation.

Figure 3

Survival outcomes of chemotherapy/chemotherapy +ICIs after PSM. (A) K-M curves of OS stratified by chemotherapy/chemotherapy +ICIs after PSM; (B) K-M curves of PFS stratified by chemotherapy/chemotherapy +ICIs after PSM; OS, overall survival; PFS, progression free survival; PSM, propensity score matching; ICIs, immune checkpoint inhibitors. HR, hazard ratio; CI, confidence interval.

Figure 4

Tumor response and treatment-related AEs in all LS-SCLC patients. (A) Tumor response in all LS-SCLC patients. (B) Treatment-related AEs in all LS-SCLC patients. AEs, adverse events; LS-SCLC, limited-stage small cell lung cancer; ICIs, immune checkpoint inhibitors; PR, partial response; SD, stable disease; ORR, objective response rate; DCR, disease control rate; PD-1, programmed cell death protein 1; PD -L1, programmed cell death ligand 1.

Figure 5

Survival outcomes of different ICIs (PD-1/PD-L1). (A) K-M curves of OS stratified by different ICIs (PD-1/PD-L1); (B) K-M curves of PFS stratified by different ICIs (PD-1/PD-L1); OS, overall survival; PFS, progression free survival; ICIs, immune checkpoint inhibitors. HR, hazard ratio; CI, confidence interval; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1.