OBJECTIVES : Metastatic renal cell carcinoma (mRCC) is the most common type of kidney cancers. Disease-specific survival for mRCC has been significantly improved with the introduction of new targeted agents since 2005. However, there is a lack of head-to-head clinical trials comparing the efficacy between therapies. This study compared indirectly progression-free survival (PFS) and overall survival (OS) among first-line and second-line therapies in patients with mRCC using network meta-analysis (NMA).

METHODS : The PubMed, MEDLINE, Cochrane Library, and Web of Science were searched to identify phase II or III randomized controlled trials (RCTs) of targeted and biological therapies in patients with mRCC published between January 2000 and November 2018. The Bayesian fixed effect NMA was performed to evaluate relative PFS and OS of first-line and second-line therapies of axitinib, bevacizumab, cabozantinib, everolimus, lenvatinib, nivolumab, ipilimumab, pazopanib, sorafenib, sunitinib, temsirolimus, tivozanib. Endpoints were compared using hazard ratio (HR) and 95% credible interval (CrI). The surface under the cumulative ranking curve (SUCRA) was estimated to assess the probability of being the best treatment.

RESULTS : In total, 26 RCTs (First-line: 18, Second-line: 10) with 12,344 patients were included in the NMA. For the first-line therapy, cabozantinib had a high likelihood of being preferred treatment (SUCRA: 96%) for PFS and a lowest relative risk of disease progression or death compared to placebo (HR=0.26, 95% CrI=0.14-0.44). Nivolumab+ipilimumab showed 94% SUCRA for OS (HR=0.48, 95% CrI=0.18-1.01). For the second-line therapy, cabozantinib had the lowest risk (HR=0.17, 95% CrI=0.12-0.24) on PFS. Axitinib had 78% SUCRA of being a first rank option in the second-line therapy regarding OS (HR=0.55, 95% CrI=0.41-0.72).

CONCLUSIONS : With respect to PFS and OS improvement, cabozantinib and nivolumab+ipilimumab are likely to be the preferred options for the first-line therapy and cabozantinib and axitinib for the second-line therapy in the mRCC management.