Aims
To determine the safety and effectiveness of immunotherapy in addition to platinum-doublet chemotherapy for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the first-line setting.
Methods
Electronic databases (Cochrane Central Register for Controlled Trials, Medline, Embase) and conference proceedings were systematically searched for relevant studies published until 21 August 2020. Phase III randomised controlled trials of patients with ES-SCLC where immunotherapy plus chemotherapy (experimental group) was compared to chemotherapy alone (control group) as first-line therapy were included. Data was extracted and risk of bias assessed by two reviewers based on PRISMA guidelines. The effect estimate was expressed as a hazard ratio (HR) to pool time-to-event data for survival analysis.
Results
Four eligible studies with 2347 participants were included for analysis. Four different immune checkpoint inhibitors were evaluated including two PD-L1 inhibitors (atezolizumab and durvalumab), one PD-1 inhibitor (pembrolizumab), and one CTLA-4 inhibitor (ipilimumab). A low risk of bias was seen in all studies. Data was pooled using a random-effects model to evaluate overall survival (OS) and progression free survival (PFS). There was a statistically significant improvement in median OS (HR 0.81, 95% CI 0.70-0.93, p=0.003) and PFS (HR 0.80, 95% CI 0.74-0.87, p<0.00001). In subgroup analyses, the addition of immunotherapy did not result in an OS benefit in patients with brain metastases (HR 1.18, 95% CI 0.82-1.70). In terms of safety, there was no statistically significant difference between both groups for grade 3 or 4 adverse events (RR 1.02, 95% CI 0.96-1.09).
Conclusion
Current literature suggests that combination treatment with immunotherapy provides a small but statistically significant OS benefit in comparison with chemotherapy alone as first line therapy in patients with advanced SCLC. However, patients with brain metastases may not derive as much benefit.