PEMBROLIZUMAB, a highly selective, humanised monoclonal antibody targeting programmed cell death 1 (PD-1), has a superior safety profile and improved survival rates compared with chemotherapy when used as second-line treatment for advanced urothelial carcinoma, results from a recent Phase III trial revealed.
This open-label, international trial featured 542 patients with advanced urothelial cancer that had either recurred or progressed after platinum-based chemotherapy. The patients were randomly assigned to receive either pembrolizumab at a dose of 200 mg every 3 weeks, or chemotherapy with paclitaxel, docetaxel, or vinflunine at the discretion of the study investigators.
The investigators found that median overall survival in the pembrolizumab study arm was 10.3 months, which compared favourably with 7.4 months in the chemotherapy arm. Furthermore, the risk of death in pembrolizumab-treated patients was greatly reduced by 27%. Considering the findings in greater detail, it was shown that median overall survival in patients with a tumour PD-1 ligand combined positive score of ≥10% was higher in the pembrolizumab arm compared with chemotherapy arm, at 8.0 months and 5.2 months, respectively; this was a 43% reduced risk of death in the pembrolizumab arm. Furthermore, pembrolizumab appeared to have an enhanced safety profile, with 60.9% of those treated with pembrolizumab reporting treatment-related adverse events compared with 90.2% of those on the chemotherapy regimen. Finally, the duration of progression-free survival was not found to be significantly different between the two study arms in either the total population of patients with a tumour PD-1 ligand combined positive score of ≥10%.
In an editorial accompanying the results of the study, Dr Guru Sonpavde, Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA, discussed the benefits of these findings, explaining: “The longer survival and lower rates of toxic effects with pembrolizumab than with chemotherapy confer an improved therapeutic index in these generally elderly patients with coexisting conditions.” He went on to comment about the future of treatments, noting: “As we celebrate the major advance that is provided by pembrolizumab, it is important to remember that this remains an incremental advance overall, although the responses were remarkably durable.”