Cabozantinib versus everolimus, nivolumab, axitinib, sorafenib and best supportive care: A network meta-analysis of progression-free survival and overall survival in second line treatment of advanced renal cell carcinoma

Abstract

BackgroundRelative effect of therapies indicated for the treatment of advanced renal cell carcinoma (aRCC) after failure of first line treatment is currently not known. The objective of the present study is to evaluate progression-free survival (PFS) and overall survival (OS) of cabozantinib compared to everolimus, nivolumab, axitinib, sorafenib, and best supportive care (BSC) in aRCC patients who progressed after previous VEGFR tyrosine-kinase inhibitor (TKI) treatment.Methodology & findingsSystematic literature search identified 5 studies for inclusion in this analysis. The assessment of the proportional hazard (PH) assumption between the survival curves for different treatment arms in the identified studies showed that survival curves in two of the studies did not fulfil the PH assumption, making comparisons of constant hazard ratios (HRs) inappropriate. Consequently, a parametric survival network meta-analysis model was implemented with five families of functions being jointly fitted in a Bayesian framework to PFS, then OS, data on all treatments. The comparison relied on data digitized from the Kaplan-Meier curves of published studies, except for cabozantinib and its comparator everolimus where patient level data were available. This analysis applied a Bayesian fixed-effects network meta-analysis model to compare PFS and OS of cabozantinib versus its comparators. The log-normal fixed-effects model displayed the best fit of data for both PFS and OS, and showed that patients on cabozantinib had a higher probability of longer PFS and OS than patients exposed to comparators. The survival advantage of cabozantinib increased over time for OS. For PFS the survival advantage reached its maximum at the end of the first year’s treatment and then decreased over time to zero.ConclusionWith all five families of distributions, cabozantinib was superior to all its comparators with a higher probability of longer PFS and OS during the analyzed 3 years, except with the Gompertz model, where nivolumab was preferred after 24 months.

Targeted therapies for previously treated advanced or metastatic renal cell carcinoma: systematic review and network meta-analysis

“…Two NMAs of different subsets of treatments for previously treated amRCC have recently been published 39 40. Unlike these studies, this review provides an alternative approach and a comparison between all recently approved treatments.…”

Non-Clear Cell Renal Cell Carcinoma - Pathology and Treatment Options

“…Recently, therapy options with cabozantinib or immune checkpoint inhibitors such as nivolumab alone or in combination with ipilimumab have shown an OS advantage in 2nd and 1st line therapy of ccRCC versus sorafenib [8] or sunitib [9]. Checkpoint inhibitors might be a new and very interesting option for metastatic nccRCC for which the therapeutic options are limited.…”

Does an Alternative Sunitinib Dosing Schedule Really Improve Survival Outcomes Over a Conventional Dosing Schedule in Patients with Metastatic Renal Cell Carcinoma? An Updated Systematic Review and Meta-Analysis

“…Therefore, for these types of studies, adjusted findings are usually preferred for meta-analysis [26]. In addition, we believe that this conflicting OS result may depend not only on statistical limitations, but also on the response to the drugs following sunitinib, such as axitinib, cabozantinib, and immune checkpoint inhibitors [27,28]. The currently included studies did not specify drug schedules after sunitinib, thus it is difficult to investigate adequate drug sequencing after sunitinib.…”