Immunotherapy in Extensive Stage Small-Cell Lung Cancer in First-Line and Second-Line Setting: A Systematic Review...

Area of Science:

• Oncology
• Immunotherapy
• Clinical Trials

Background:

• Small-cell lung cancer (SCLC) exhibits high relapse rates and poor prognosis despite initial chemotherapy response.
• Extended stage SCLC (ES-SCLC) treatment remains challenging, necessitating novel therapeutic strategies.
• Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic class in various cancers.

Purpose of the Study:

• To systematically review and meta-analyze the efficacy and safety of ICIs in ES-SCLC treatment.
• To evaluate the role of ICIs across different lines of therapy in ES-SCLC.
• To identify potential benefits and risks associated with ICI use in ES-SCLC patients.

Main Methods:

• Systematic review and meta-analysis of randomized controlled trials (RCTs) published between 2010 and 2025.
• Databases searched include Medline (PubMed), EMBASE, and Cochrane Library, supplemented by conference proceedings.
• Primary endpoints: overall survival (OS) and progression-free survival (PFS); secondary endpoints: objective response rate (ORR) and adverse events.

Main Results:

• ICIs significantly decreased the risk of death by 19% (HR: 0.81) and disease progression by 22% (HR: 0.78) in first-line ES-SCLC.
• OS and PFS benefits were observed only in the first-line setting, with a detrimental effect on PFS in the second-line.
• ICIs improved ORR but were associated with a significant increase in grade 3+ diarrhea.

Conclusions:

• ICIs demonstrate efficacy and an acceptable safety profile in first-line ES-SCLC treatment.
• Second-line ICI monotherapy in ES-SCLC is not recommended due to lack of benefit and potential harm.
• Development of predictive biomarkers is crucial for optimizing long-term outcomes with ICIs in ES-SCLC.