Immune checkpoint inhibitors as first line in advanced melanoma: Evaluating progression‐free survival based on reconstructed individual patient data

Abstract

Abstract Background In patients with advanced melanoma, immune‐checkpoint inhibitors (ICIs) represent the mainstay for first line treatment. Recently, relatlimab+nivolumab was proposed as a new combination therapy. This review was aimed at summarizing the current data of effectiveness for ICIs. Progression‐free survival (PFS) was the endpoint of our analysis. Methods After a standard literature search, Phase II/III studies comparing different ICI regimens in previously untreated advanced melanoma patients were analyzed. Patient‐level data were reconstructed from Kaplan–Meier curves by application of the IPDfromKM method. These reconstructed datasets were used to perform indirect comparisons between treatments. Standard statistical testing was used, including hazard ratio and medians. A secondary analysis employed the restricted mean survival time. Results Six trials were included in our analysis. Information on PFS from these trials was pooled according to the following treatments: nivolumab or pembrolizumab as monotherapy, or in combination with ipilimumab, and relatlimab + nivolumab. Pembrolizumab+ipilimumab showed significantly better PFS compared with the other treatments; nivolumab+ipilimumab ranked second; the other treatments showed a similar survival pattern. Conclusions The picture of comparative effectiveness resulting from our analysis is complex. The IPDfromKM method is advantageous because it accounts for the length of follow‐up but loses the balance between treatment group and controls determined by randomization. Based on indirect comparisons, the combination of pembrolizumab+ipilimumab showed a particularly high efficacy, and so deserves further investigation. While the effect of between‐trial differences in inclusion criteria plays an important role, our results do not support the proposal of relatlimab+nivolumab as a new standard of care.

Keywords

• advanced melanoma
• individual patient data
• IPDfromKM method
• ipilimumab
• nivolumab
• patient data reconstruction