Utilization and efficacy of second-line targeted therapy in metastatic renal cell carcinoma: data from a national registry

Abstract

BackgroundIt is well known that patient characteristics and survival outcomes in randomized trials may not necessarily be similar to those in real-life clinical practice. The aim of the present study was to analyse second line treatment strategies in the real-world practice and to estimate the outcomes of patients treated with second-line targeted therapy for metastatic renal cell carcinoma (mRCC).MethodsThis is a retrospective, registry-based study using data from the national registry of targeted therapies for mRCC. The RENIS registry contains data on 3049 patients who started the therapy with at least one targeted agent before 31 December, 2014. Of these patients, 1029 had a record of at least two different targeted therapies and sufficient data for analysis. Survival analysis was carried out using the Kaplan-Meier method. Statistical significance of differences in survival between subgroups was assessed using the log-rank test.ResultsThe median overall survival from the start of second-line treatment was 17.0 months (95% confidence interval [CI] 14.5–19.5 months), 17.1 months (95% CI 14.5–19.8), and 15.4 months (95% CI 11.0–19.7) for second-line everolimus, sorafenib, and sunitinib, respectively. Patients receiving second-line everolimus were older at the start of second-line treatment, more likely to have metachronous disease, and less likely to be previously treated with cytokines or to continue to third-line treatment than patients treated with second-line sunitinib or sorafenib. Progression-free survival (PFS) correlated with PFS on first-line treatment only for everolimus.ConclusionsIn this retrospective study, no significant differences in survival were observed between the cohorts treated with different second-line agents including everolimus, sorafenib, and sunitinib.

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

“…Five of these studies have been excluded from this review because of the update of the scope excluding sunitinib as it is not recommended at second line in the most up-to-date ESMO guidance for RCC 12. Five new studies, one RCT and four retrospective chart reviews were identified in the update and extension searches (including terms for lenvatinib with everolimus) run in January 2018, making a total of 12 included studies 13–15 19 20 27–33…”

“…Twelve studies (n=5144) met the inclusion criteria (table 1): five RCTs (one double-blind28 and four open-label13 15 20 28) and seven observational studies19 27 29–33 (retrospective cohort studies). Sample sizes varied from 101 (HOPE 205)15 to 821 (CheckMate 025)14 participants.…”

“…AXIS20 also included people who had not received prior anti-VEGF treatment, but OS and PFS data were available for the subset who had. In eight of the included studies, people had only received one prior VEGF-targeted treatment14 19 29–34; the remaining five studies allowed one or more prior treatments 13 14 27 35. Populations were predominantly male and Caucasian, and mean age was generally between 55 and 65 years.…”

“…Overall ROBINS-I ratings were at best moderate, for OS,19 29 31 and serious risk of bias for PFS. One study was at critical risk of bias for both PFS and OS,33 which was excluded from the sensitivity analyses. In all studies the potential for inadequate control for confounding was thought to increase the risk of bias.…”

“…One of the observational studies was publicly funded,33 two studies did not report their funding source27 32 and the remaining observational studies and all RCTs were sponsored by various pharmaceutical companies. Risk of bias assessments for all included studies are provided in the online supplementary tables 3 and 4.…”