Choosing the best first-line therapy for extensive-stage small-cell lung cancer: anti-PD-1 or anti-PD-L1 inhibitors?

BACKGROUND

This study addresses the lack of a comprehensive meta-analysis comparing the efficacy and safety of first-line anti-blocking the programmed cell death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1) therapies in patients with extensive-stage small-cell lung cancer, using reconstructed individual patient data.

METHODS

Through systematic review, we extracted relevant studies from PubMed and EMBASE databases, spanning January 1, 2010 to November 28, 2024. Only phase III randomized controlled trials assessing anti-PD-1 inhibitors plus chemotherapy (CT) versus anti-PD-L1 inhibitors plus CT were selected. To compare survival outcomes, we employed WebPlotDigitizer and R software for survival curve reconstruction, aiming to elucidate the comparative effectiveness and safety of the 2 therapies.

RESULTS

Our analysis of 7 randomized controlled trials, involving 3339 patients, revealed no significant difference in progression-free survival (PFS) or overall survival (OS) between anti-PD-1 inhibitors plus CT and anti-PD-L1 inhibitors plus CT. The combined 6-, 12-, and 18-month PFS rates were 42.4% versus 43.3%, 19.9% versus 17.0%, and 14.6% versus 13.6% for the anti-PD-1 and anti-PD-L1 groups, respectively (hazard ratio: 0.98, 95% confidence interval: 0.88-1.09, P = .691). The combined 6-, 12-, 18-, and 24-month OS rates were 86.6% versus 85.5%, 58.7% versus 56.9%, 38.8% versus 36.8%, and 28.9% versus 25.4% for the anti-PD-1 and anti-PD-L1 groups, respectively (hazard ratio: 0.94, 95% confidence interval: 0.84-1.06, P = .305). The analysis showed a slightly lower incidence of grade ≥3 adverse events (AEs), serious AEs, any-grade immune-related adverse events, grade ≥3 immune-related adverse events, and events leading to death or treatment discontinuation in the anti-PD-L1 group compared to the anti-PD-1 group (P < .001). However, no significant differences were observed in the risk of any-grade AEs.

CONCLUSION

This research provides detailed analyses of PFS, OS, and treatment safety for these 2 treatment regimens, making it a valuable resource for clinicians in routine care. Our results demonstrate that both anti-PD-1 and anti-PD-L1 therapies, when combined with chemotherapy, are equally effective. However, anti-PD-L1 therapies appear to offer a safer first-line treatment option for extensive-stage small-cell lung cancer.