4.6 Article

LAG3-PD1 or CTLA4-PD1 Inhibition in Advanced Melanoma: Indirect Cross Comparisons of the CheckMate-067 and RELATIVITY-047 Trials

期刊

CANCERS
卷 14, 期 20, 页码 -

出版社

MDPI
DOI: 10.3390/cancers14204975

关键词

PD-1; CTLA4; LAG3; melanoma; immunotherapy

类别

资金

  1. National Science Foundation of China [82103586]
  2. China Postdoctoral Science Foundation [2021M703728]
  3. Guangdong Provincial Natural Science Foundation [2021A1515012369]
  4. Beijing Xisike Clinical Oncology Research Foundation [Y-tongshu2021/qn-0227]

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The efficacy of LAG3-PD1 and CTLA4-PD1 inhibition in previously untreated advanced melanoma patients is similar, but LAG3-PD1 inhibition appears to have earlier survival benefits and fewer adverse events.
Simple Summary In the past few decades, targeted therapy and immunotherapy have transformed tremendously the chances of survival. Checkpoint inhibitors that block programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways hold the most promise. However, more than half of the patients treated with CTLA-4-PD1 inhibition suffered from grade 3 or 4 treatment-related adverse events (TRAEs). Recently, Tawbi et al. reported the initial results of the phase 2-3 RELATIVITY-047 trial which evaluated LAG3-PD1 inhibition of relatlimab plus nivolumab in patients with previously untreated advanced melanoma. Here, we performed an indirect cross-comparison of LAG3-PD1 and CTLA4-PD1 inhibition in patients with previously untreated advanced melanoma by deriving individual patient survival data and safety profiles. We found that the PFS of LAG3-PD1 and CTLA4-PD1 inhibition were similar. Compared with CTLA4-PD1-inhibition, LAG3-PD1 inhibition tended to exhibit earlier survival benefit and lesser TRAEs. Objective: To compare the inhibition of LAG3-PD1 versus the inhibition of CTLA-4-PD1 in patients with previously untreated advanced melanoma. Methods: The individual participant data (IPD) were extracted from the KM plots using a graphical reconstructive algorithm. 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. 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 plus relatlimab (LAG3 inhibitor) versus nivolumab plus ipilimumab (CTLA4 inhibitor) was 1.19 (95% confidence interval [CI] 0.96 to1.48). The 24-months RMST of nivolumab plus relatlimab versus nivolumab was 2.35 (95% CI 0.77-3.94) months, compared with 1.87 (95% CI, 0.25-3.49) months for nivolumab plus ipilimumab versus nivolumab. The Bayesian hierarchical model showed that patients treated with nivolumab plus relatlimab had earlier PFS benefits than those with nivolumab plus ipilimumab. Grade 3 or 4 treatment-related adverse events occurred in 18.9% of patients using nivolumab plus relatlimab and 55.0% of patients using nivolumab plus ipilimumab. Conclusions: These findings suggest that the PFS of LAG3-PD1 and CTLA4-PD1 inhibition were similar and LAG3-PD1 inhibition exhibited earlier survival benefit and lesser TRAEs.

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