Combinations of immunotherapies in the first-line treatment of urothelial cancer: systematic review and meta-analysis of individual patient data

Oncology

Platinum-based chemotherapy represents the standard of care for the first-line treatment of advanced urothelial carcinoma (mUC). The benefit of adding immune checkpoint inhibitors (ICIs) to platinum-based chemotherapy has recently been investigated. The authors conducted a meta-analysis of individual patient data (IPD) from phase 3 clinical trials comparing ICI-based therapies.

A systematic literature search was performed in the MEDLINE and CENTRAL databases. Results were filtered by including only reports of clinical trials or randomised clinical trials from 2018 to 2023, including 3047 patients from four clinical trials (EV302, CHECKMATE-901, IMVIGOR130, KEYNOTE-361). A meta-analysis of individual patient data was performed using Kaplan-Meier curve reconstruction. The primary endpoints were overall survival and progression-free survival of Pembrolizumab + EV compared with the experimental arms of the other immunotherapy + chemotherapy trials.

Analysis of overall survival showed an advantage of IPD in the EV302 trial over all other trials. For EV302 vs KEYNOTE-361, the HR was 0.51; for EV302 vs IMVIGOR130, the HR was 0.47; and for EV302 vs CHECKMATE-901, the HR was 0.66 (95% CI 0.51-0.85). In the analysis of progression-free survival, the EV302 group showed a statistically significant advantage over CHECKMATE-901 (HR 0.66) and over IMVIGOR130 (HR 0.51).

LIMITATIONS: Using reconstructed DPI curves, it was not possible to adjust covariates at the patient level, and the heterogeneity of the included population may have affected the pooled results.

CONCLUSIONS: The EV302 experimental arm showed better overall and progression-free survival compared with the other immunochemotherapy combinations. An immunochemotherapy combination strategy at the start of treatment for advanced urothelial carcinoma appears to be superior in terms of overall and progression-free survival compared with platinum-based chemotherapy alone. EV-Pembrolizumab showed better results than avelumab, rather than other immunochemotherapy combinations. However, given the heterogeneity of these studies, longer follow-up and prospective trials are needed to confirm these data.

Source(s) :
Di Civita MA; Torchia A; Santini D; Marinelli D; Magro V; Cerro M; Pappalardo L; Maltese G; Santamaria F; Zacco L; Buccilli D; Dehghanpour A; Speranza I; Sciarra A; Panebianco V; Roberto M ;

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