Effect of Sex on the Oncological Outcomes in Response to Immunotherapy and Antibody-drug Conjugates in Patients with Urothelial and Kidney Cancer: A Systematic Review and a Network Meta-analysis.

BACKGROUND AND OBJECTIVE

Immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) herald a transformative era in metastatic renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) treatment, amid acknowledged sex-based disparities in these cancers. We conducted a systematic review and network meta-analysis (NMA) to identify sex-specific differences in the efficacy of ICI/ADC monotherapy or combination therapies for RCC and TCC survival, in metastatic and adjuvant settings.

METHODS

A systematic search was conducted up to October 2023 for English articles on ICIs and ADCs as systemic therapies (ICIs in first-line and adjuvant treatment for RCC, ICIs and ADCs in first- and second-line treatment for TCC). Randomised clinical trials were considered. The primary objective was overall survival (OS) of ICIs and ADCs between males and females. The secondary outcomes included progression-free survival, overall response rate, disease-free survival, and recurrence-free survival. Treatment efficacy was evaluated by sex via odds ratios (ORs) and confidence intervals compared with controls. Log ORs were used for creating a frequentist NMA. This meta-analysis was registered on PROSPERO (CRD42023468632).

KEY FINDINGS AND LIMITATIONS

Eighteen articles met the inclusion criteria. Females had an advantage for RCC-adjuvant treatment for atezolizumab (log OR [SE] = -0.57 ± 0.25, p = 0.024) in OS. Males showed a survival advantage in TCC second-line treatment for ADC-Nectin 4 (log OR [SE] = 0.65 ± 0.28, p = 0.02). No other significant results were shown.

CONCLUSIONS AND CLINICAL IMPLICATIONS

The NMA revealed gender-specific variations in ICI and ADC responses for RCC and TCC, offering insights for personalised cancer care and addressing disparities in cancer care and outcomes.

PATIENT SUMMARY

In this systematic review, we looked at the sex differences for metastatic renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) for antibody-drug conjugates and immune checkpoint inhibitors. In our analysis, female and male sex has better overall survival for adjuvant and second-line therapies for RCC and TCC, respectively. Urgent research on gender-specific cancer therapies is imperative.