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Meta-Analysis
. 2023 Jul;41(7):1763-1774.
doi: 10.1007/s00345-023-04412-0. Epub 2023 May 20.

Impact of sex on the efficacy of immune checkpoint inhibitors in kidney and urothelial cancers: a systematic review and meta-analysis

Takafumi Yanagisawa  1   2 , Tatsushi Kawada  1   3 , Fahad Quhal  1   4 , Kensuke Bekku  1   3 , Ekaterina Laukhtina  1   5 , Pawel Rajwa  1   6 , Markus von Deimling  1   7 , Muhammad Majdoub  1   8 , Marcin Chlosta  1   9 , Benjamin Pradere  1   10 , Keiichiro Mori  2 , Takahiro Kimura  2 , Manuela Schmidinger  1 , Pierre I Karakiewicz  11 , Shahrokh F Shariat  12   13   14   15   16   17
Affiliations
Meta-Analysis

Impact of sex on the efficacy of immune checkpoint inhibitors in kidney and urothelial cancers: a systematic review and meta-analysis

Takafumi Yanagisawa et al. World J Urol. 2023 Jul.

Abstract

Purpose: To analyze and summarize the efficacy of immune checkpoint inhibitor (ICI) alone or in combination therapy for renal cell carcinoma (RCC) and urothelial carcinoma (UC) stratified by sex.

Methods: Three databases were queried in October 2022 for randomized controlled trials (RCTs) analyzing RCC and UC patients treated with ICIs. We analyzed the association between sex and the efficacy of ICIs in RCC and UC patients across several clinical settings. The outcomes of interest were overall survival (OS) and progression-free survival for the metastatic setting and disease-free survival (DFS) for the adjuvant setting.

Results: Overall, 16 RCTs were included for meta-analyses and network meta-analyses. In the first-line treatment of metastatic RCC (mRCC) and UC (mUC) patients, ICI-based combination therapies significantly improved OS compared to the current standard of care, regardless of sex. Adjuvant ICI monotherapy reduced the risk of disease recurrence in female patients with locally advanced RCC (pooled hazard ratio [HR]: 0.71, 95% confidence interval [CI] 0.55-0.93) but not in male patients, and, conversely, in male patients with muscle-invasive UC (pooled HR: 0.80, 95%CI 0.68-0.94) but not in female patients. Treatment ranking analyses in the first-line treatment of mRCC and mUC showed different results between sexes. Of note, regarding adjuvant treatment for RCC, pembrolizumab (99%) had the highest likelihood of improved DFS in males, whereas atezolizumab (84%) in females.

Conclusions: OS benefit of first-line ICI-based combination therapy was seen in mRCC and mUC patients regardless of sex. Sex-based recommendations for ICI-based regimens according to the clinical setting may help guide clinical decision-making.

Keywords: Adjuvant; Advanced; Gender; Immune checkpoint inhibitors; Metastatic; Renal cell carcinoma; Sex; Urothelial carcinoma.

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Conflict of interest statement

Takahiro Kimura is a paid consultant/advisor of Astellas, Bayer, Janssen and Sanofi. Shahrokh F. Shariat received follows: Honoraria: Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Roche, Takeda Consulting or Advisory Role: Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Pierre Fabre, Roche, Takeda Speakers Bureau: Astellas, Astra Zeneca, Bayer, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Richard Wolf, Roche, Takeda, The other authors declare no conflicts of interest associated with this manuscript.

Figures

Fig. 1
Fig. 1
Forest plots showing association of survival outcomes and ICI therapy for RCC stratified by sex; OS A and PFS B for 1st-line ICI-based systemic combination therapy, and C DFS for adjuvant ICI therapy for locally advanced RCC
Fig. 1
Fig. 1
Forest plots showing association of survival outcomes and ICI therapy for RCC stratified by sex; OS A and PFS B for 1st-line ICI-based systemic combination therapy, and C DFS for adjuvant ICI therapy for locally advanced RCC
Fig. 2
Fig. 2
Forest plots and SUCRA graph from NMAs for A OS in mRCC patients treated with 1st-line systemic treatment and B DFS in locally advanced RCC patients treated with adjuvant ICI therapy
Fig. 3
Fig. 3
Forest plots showing association of survival outcomes and ICI therapy for UC stratified by sex; A OS for 1st-line ICI-based systemic combination therapy and B DFS for adjuvant ICI therapy for locally advanced UC
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