First-line therapy for elderly patients with advanced renal cell carcinoma in the immuno-oncology era: a network meta-analysis

Background: Tyrosine kinase inhibitors (TKI) or immune checkpoint blockade (ICB), either alone or in combination, confers a significant overall survival (OS) benefit for metastatic RCC in the first-line setting. However, guidance for optimal treatment selection in elderly patients remains limited. Methods: A database search was performed to identify eligible randomized controlled trials (RCTs) evaluating first-line regimens for patients with advanced RCC older than 65 years old. The primary outcomes were progression-free survival (PFS) and OS. Indirect comparisons of available regimens were estimated using a random-effects network meta-analysis. Results: A total of 14 and five RCTs were eligible for PFS and OS analyses. Compared with sunitinib, pembrolizumab plus axitinib (HR 0.68, 95% CI 0.48–0.97) and pembrolizumab plus lenvatinib (HR 0.61, 95% CI 0.4–0.94) were associated with improved OS. Pembrolizumab plus lenvatinib, nivolumab plus cabozantinib, pembrolizumab plus axitinib, and cabozantinib alone each showed improved PFS over sunitinib. Among these, pembrolizumab plus lenvatinib showed better PFS than pembrolizumab plus axitinib (HR 0.58, 95% CI 0.37–0.91), but no PFS difference compared to nivolumab plus cabozantinib (HR 0.63, 95% CI 0.39–1.03) and cabozantinib alone (HR 0.84, 95% CI 0.40–1.77). Network ranking showed pembrolizumab plus lenvatinib provided the favored OS and PFS benefit for elderly patients. Conclusions: The combination of ICB with TKI such as pembrolizumab plus lenvatinib needs to be considered over monotherapy in the elderly population, but further validation using real-world data or prospective trials is necessary to confirm the efficacy and safety of first-line regimens for the geriatric population with advanced RCC.