The Optimal First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer Based on Liver Metastasis Status: A Network...

Area of Science:

• Oncology
• Immunotherapy
• Pharmacology

Background:

• Extensive-stage small-cell lung cancer (ES-SCLC) presents a significant therapeutic challenge.
• First-line treatment strategies are evolving with the advent of immune checkpoint inhibitors.
• The presence of liver metastases (LM) may influence treatment efficacy in ES-SCLC.

Purpose of the Study:

• To compare the effectiveness of first-line programmed cell death (ligand) [PD-(L)1] blockade-based regimens in ES-SCLC patients.
• To evaluate treatment efficacy in ES-SCLC patients with and without liver metastases (LM).
• To identify optimal first-line treatment strategies for ES-SCLC based on PD-(L)1 blockade.

Main Methods:

• A network meta-analysis of randomized controlled trials (RCTs) was conducted.
• Studies compared chemo-immunotherapy (CIT) against chemotherapy (CT) in ES-SCLC patients, stratified by LM status.
• Overall survival (OS) and progression-free survival (PFS) were assessed using hazard ratios (HRs) and 95% confidence intervals (CIs).

Main Results:

• Seven RCTs involving 3658 ES-SCLC patients were analyzed.
• In patients with LM, anti-PD-1 + CT (HR, 0.67) and anti-PD-L1 + CT + anti-angiogenesis (HR, 0.84) significantly improved OS versus CT alone.
• The anti-PD-1 + CT regimen showed the highest cumulative probability (91.6%) for OS improvement in LM patients. For non-LM patients, anti-angiogenesis + anti-PD-L1 + CT ranked highest (95.5% cumulative probability for OS).

Conclusions:

• Chemo-immunotherapy (CIT) demonstrates efficacy in ES-SCLC patients irrespective of liver metastasis (LM) status.
• For ES-SCLC patients with LM, combining PD-1 blockade with chemotherapy represents the optimal first-line strategy.
• For ES-SCLC patients without LM, the combination of anti-angiogenesis, PD-L1 blockade, and chemotherapy is the most beneficial regimen.