Abstract
e21511 Background: There remain unmet needs to identify novel immune checkpoint inhibitors to improve the benefit-risk profile of immunotherapy for advanced melanoma. The comparison between LAG3-PD1 inhibition and CTLA4-PD1 inhibition was lacked. To compare the inhibition of lymphocyte-activation gene 3 (LAG3) plus programmed cell death 1 (PD-1) versus the inhibition of cytotoxic T-lymphocyte antigen 4 (CTLA-4) plus PD-1 in patients with previously untreated advanced melanoma. Methods: The individual participant data (IPD) data were extracted from the KM plots using a graphical reconstructive algorithm through eligible. Log-rank, Cox proportional hazard model, Bayesian hierarchical model with time-varying hazard ratio (HR) effect, and restricted mean survival time (RMST) were performed to estimate survival benefits. The primary endpoint was progression-free survival. Results: The CheckMate-067 (N = 630) and RELATIVITY-047 (N = 714) trials were included for analysis. The graphical reconstructive algorithm showed that IPD had similar HRs and log-rank values as the original plots. The HR of nivolumab-relatlimab (LAG3 inhibitor) versus nivolumab-ipilimumab (CTLA4 inhibitor) was 1.19 (95% confidence interval [CI] 0.96 to1.48). The 24-months RMST of nivolumab-relatlimab versus nivolumab alone was 2.35 (95% CI 0.77 to 3.94) months, compared with 1.87 (95% CI 0.25-3.49) months for nivolumab-ipilimumab versus nivolumab. The Bayesian hierarchical model showed that patients treated with nivolumab-relatlimab had earlier PFS benefits than those with nivolumab-ipilimumab. Grade 3 or 4 treatment-related adverse events occurred in 18.9% of patients using nivolumab-relatlimab and 55.0% of patients using nivolumab-ipilimumab. Conclusions: These findings suggest that the PFS of LAG3-PD1 and CTLA4-PD1 inhibition were similar and that LAG3-PD1 inhibition tended to exhibit earlier survival benefit and lesser TRAEs.
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