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Published on: September 25, 2018
Efficacy and safety of first-line PD-1/PD-L1 inhibitor combinations for extensive-stage small-cell lung cancer: a
Huijuan Li1,2, Hedong Han2, Chuling Li3
1Department of Respiratory and Critical Care Medicine, Jinling Hospital, the First School of Clinical Medicine, Southern Medical University (Guangzhou), Nanjing, China.
Objectives:
Several randomized controlled trials (RCTs) indicated that first-line programmed cell death protein-1/death-ligand 1 inhibitors plus chemotherapy (PD-1/PD-L1 + chemo) led to survival benefits in extensive-stage small-cell lung cancer (ES-SCLC) compared with platinum-based chemotherapy. This study aims to identify the optimal PD-1/PD-L1 + chemo combination strategy.
Methods:
We included RCTs comparing PD-1/ PD-L1 + chemo versus chemo alone in ES-SCLC. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade ⩾3 treatment-related adverse events were considered. Odds ratios (ORs), hazard ratios (HRs), and their 95% confidence intervals (CIs) were extracted.
Results:
Six RCTs with 2600 patients were analyzed in this Bayesian network meta-analysis. Results showed that adding PD-1/PD-L1 inhibitors to chemotherapy led to significant benefits in OS (HR = 0.72, 95% CI: 0.66-0.79), PFS (HR = 0.69, 95% CI: 0.63-0.75), and ORR (OR = 1.32, 95% CI: 1.12-1.56), and no differences in toxicity were found (OR = 1.09, 95% CI: 0.92-1.30). Serplulimab plus chemotherapy was found to provide the best OS (HR = 0.63, 95% CI: 0.49-0.82), the best PFS (HR = 0.47, 95% CI: 0.38-0.59), and the best ORR (OR = 1.7, 95% CI: 1.15-2.53). Moreover, although there were no difference between PD-L1 + chemo and PD-1 + chemo regarding OS (HR = 0.99, 95% CI: 0.91-1.08) and ORR (OR = 1.27, 95% CI: 0.91-1.78), PD-1 + chemo showed a significant benefit in PFS (HR = 0.82, 95% CI: 0.68-0.98) compared with PD-L1 + chemo.
Conclusions:
Serplulimab plus chemotherapy seems to be superior first-line immunotherapy combination for patients with ES-SCLC. PD-1 + chemo seems to outperform PD-L1 + chemo in PFS.
Insights
First-line programmed cell death protein-1/death-ligand 1 inhibitors plus chemotherapy significantly improve survival in extensive-stage small-cell lung cancer. Serplulimab plus chemotherapy offers superior outcomes, outperforming PD-L1 inhibitors in progression-free survival.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- First-line programmed cell death protein-1/death-ligand 1 inhibitors plus chemotherapy (PD-1/PD-L1 + chemo) demonstrate survival benefits in extensive-stage small-cell lung cancer (ES-SCLC) compared to traditional chemotherapy.
- Identifying the optimal PD-1/PD-L1 + chemo combination strategy is crucial for improving patient outcomes.
Purpose of the Study:
- To conduct a Bayesian network meta-analysis of randomized controlled trials (RCTs).
- To compare the efficacy and safety of different first-line PD-1/PD-L1 + chemo strategies in ES-SCLC.
- To identify the most effective PD-1/PD-L1 + chemo combination for ES-SCLC patients.
Main Methods:
- Systematic search and inclusion of RCTs comparing PD-1/PD-L1 + chemo versus chemotherapy alone in ES-SCLC.
- Extraction of data on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events.
- Bayesian network meta-analysis to synthesize evidence and rank treatment strategies.
Main Results:
- Six RCTs involving 2600 patients were analyzed.
- PD-1/PD-L1 + chemo significantly improved OS, PFS, and ORR compared to chemotherapy alone, with no significant difference in toxicity.
- Serplulimab + chemo demonstrated superior OS, PFS, and ORR. PD-1 + chemo showed a significant PFS benefit over PD-L1 + chemo.
Conclusions:
- Serplulimab plus chemotherapy emerges as a superior first-line immunotherapy combination for ES-SCLC.
- The findings suggest PD-1 + chemo may offer better PFS outcomes than PD-L1 + chemo in this patient population.
