A Systematic Review Comparing Sex-Specific Outcomes of Prospective Clinical Trials and Subsequent Real-World Data...

Sex-based differences in enrollment rates in clinical trials and in cancer outcomes are evident. Real-world (RW) results might differ from phase II/III trials. The aim was to compare sex-specific outcomes of RW studies and randomized controlled trials (RCT) in locally advanced or metastasized renal cell cancer (la/mRCC).

A systematic search in EMBASE, PubMed, MEDLINE, and Scopus on systemic therapies for la/mRCC was performed. Phase II/III trials, RCT, non-interventional prospective studies, retrospective studies, or case series were included. Data on overall survival (OS) and PFS (DFS for adjuvant therapies), enrollment rates, and adverse events were retrieved.

Seventy studies were included. Females were underrepresented in RCTs. Some RW analyses exceeded the epidemiological benchmark. Outcome analyses exclusively revealed advantages for males: better OS/PFS for cabozantinib (RW), better OS for nivolumab (CheckMate 025), better PFS for tivozanib (TIVO-3), better PFS for nivolumab + ipilimumab (RW), better OS for nivolumab + cabozantinib (CheckMate 9ER), better DFS for adjuvant pembrolizumab (Keynote-564). No sex-specific toxicity analyses were published in RW studies or RCT.

This systematic review enlightens sex-specific gaps in enrollment and cancer outcome, as well as the lack of sex-specific toxicity analyses. Balanced enrollment rates and reporting of sex-specific toxicity should be obligatory in evaluations of la/mRCC treatments.