Deciding on the optimal second-line (2L) treatment for metastatic clear-cell renal cell carcinoma (ccRCC) remains challenging due to the limited information comparing each of the available options and the influence of the newly expanding first-line (1L) agents.
We identified phase II/III randomized controlled trials (RCTs) evaluating 2L treatments in metastatic ccRCC. This Network Meta-analysis (NMA) evaluates the overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and severe adverse events (SAE). We used normal likelihood model to incorporate log hazard ratios (HRs), odds ratios (OR), and 95%-confidence-intervals (CI). Treatment p-scores were used for ranking. Data was analyzed in a fixed-effects model using the netmeta package in R v.1.5-0.
All therapies demonstrated some benefits over placebo. Lenvatinib + everolimus ranked first for OS (HR = 0.44; 95%CI = 0.24-0.82; p-score = 0.92), PFS (HR = 0.13; 95%CI = 0.07-0.24, p-score = 0.98), and ORR (OR = 35.95; 95%CI = 11.55-111.87; p-score = 0.93) compared to placebo, though with a higher SAE (OR = 5.27; p-score = 0.23). Cabozantinib ranked second for OS (HR = 0.57, p-score = 0.80), PFS (HR = 0.19; p-score = 0.86), and ORR (OR = 27.24, p-score = 0.84). Nivolumab was third for ORR (p-score = 0.79), fourth for OS (p-score = 0.69), fifth for PFS (p-score = 0.61), and last for SAE (p-score = 0.83). Lenvatinib monotherapy ranked worst SAE (OR = 5.89, p-score = 0.17) and third for OS and PFS. The latest drug, tivozanib, was sixth for PFS, OS, and ORR. The NMA matrix revealed no differential OS benefit between cabozantinib, lenvatinib + everolimus, and nivolumab. Other regimens had no significant OS benefit when compared to placebo.
Based on OS and PFS, the lenvtatinib + everolimus combination yielded superior, followed by cabozantinib and Lenvatinib monotherapies; all were limited by a worse SAE profile. Nivolumab and pazopanib had the lowest odds of SAEs.
Urologic oncology. 2024 Jan 11 [Epub ahead of print]
Mavis Obeng-Kusi, Jordyn J Kreutzfeldt, Ricardo J Estrada-Mendizabal, Briana M Choi, Ivo Abraham, Alejandro Recio-Boiles
Center for Health Outcomes and Pharmacoeconomic Research, Department of Pharmacy Practice and Science, University of Arizona R. Ken Coit College of Pharmacy, Tucson, AZ., University of Arizona Internal Medicine Residency Program, Tucson, AZ. Electronic address: ., Tecnologico de Monterrey School of Medicine and Health Science, Monterrey, Nuevo León, Mexico., Center for Health Outcomes and Pharmacoeconomic Research, Department of Pharmacy Practice and Science, University of Arizona R. Ken Coit College of Pharmacy, Tucson, AZ; The University of Arizona Cancer Center, Tucson, AZ., The University of Arizona Cancer Center, Tucson, AZ.