Sunitinib for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis of Real-World and Clinical Trials Data

Abstract

Background Randomized controlled trials (RCTs) have stringent inclusion criteria and may not fully represent patients seen in everyday clinical practice. Real-world data (RWD) can provide supportive evidence for the effectiveness of medical interventions in more heterogeneous populations than RCTs. Sunitinib is a widely used first-line treatment for patients with metastatic renal cell carcinoma (mRCC). Objective This is the first comprehensive meta-analysis to evaluate the efficacy of sunitinib using the novel approach of combining RCTs and RWD. Methods RCTs and RWD studies published between 2000 and 2017 were identified from PubMed, Ovid, MEDLINE, and EMBASE. Eligible studies contained a cohort of ≥ 50 adult patients with mRCC receiving first-line sunitinib treatment. The meta-analysis combined RWD and RCT treatment groups, adjusting for data type (RCT or RWD). Recorded outcomes were median progression-free survival (mPFS), median overall survival (mOS), and objective response rate (ORR). Publication bias was assessed via review of funnel plots for each outcome measure. A random effects model to account for study heterogeneity was applied to each endpoint. Sensitivity analyses evaluated the robustness of the overall estimates. Results Of the 3611 studies identified through medical database searches, 22 (15 RWD studies, 7 RCTs) met eligibility criteria and were analyzed. mPFS (18 studies), mOS (19 studies), and ORR (15 studies) were reported for aggregate measures based on 4815, 5321, and 4183 patients, respectively. Reported mPFS (RWD, 7.5-11.0 months; RCTs, 5.6-15.1 months) and ORR data (RWD, 14.0-34.6%; RCTs, 18.8-46.9%) were consistent with the overall confidence estimates (95% confidence interval [CI]) of 9.3 (8.6-10.2) months and 27.9% (24.2-32.0), respectively. Reported mOS showed greater variation in RWD (6.8-33.2 months) compared with RCTs (21.8-31.5 months), with an overall confidence estimate (95% CI) of 23.0 (19.2-27.6) months. Inspection of funnel plots and sensitivity analyses indicated that there was no publication bias for any efficacy endpoint. Sensitivity analyses showed no evidence of lack of robustness for mPFS, mOS, or ORR. Interpretation of these results is limited by differences in trial design, cohort characteristics, and missing data. Conclusions This novel, comprehensive meta-analysis validates sunitinib as an effective first-line treatment for patients with mRCC in both RCTs and everyday clinical practice. The methodology provides a framework for future analyses combining data from RCTs and RWD.

Vorolanib, an oral VEGFR/PDGFR dual tyrosine kinase inhibitor for treatment of patients with advanced solid tumors: An open-label, phase I dose escalation and dose expansion trial

“…The duration of exposure in 200 mg group and 100 mg group was 265 (range, 39−367) d and 114 (range, 56−367) d, respectively. The ORR of 22.2% and the median PFS of 9.9 months in patients treated with 200 mg of vorolanib were comparable with the results of a recent meta-analysis that reported a pooled ORR of 27.9% (95% CI: 24.2−32.0) and median PFS of 9.3 (8.6−10.2) months for sunitinib in patients with metastatic RCC ( 24 ). Notably, this study enrolled patients with advanced solid tumors who had not responded well to standard therapy; 91% of these patients had been previously treated with systemic therapy and 59% were previously treated with anti-angiogenic therapy.…”

Modernizing Regulatory Evidence with Trials and Real-World Studies

“…In fact, we know little about risks and benefits when these products are first on the market due, in part, to the increased complexities of treatment regimens and the lack of transparency and generalizability of clinical trial results [15,16]. Delivery of care is complex and a diversity of approaches to generating evidence should be embraced to maximize what can be learned and how it can inform healthcare and regulatory decisions [17]. Given the complexities of health systems, delivery of health care, and the high degree of variation in human responses to treatment, we should expect that results from RWE may differ from RCTs yet still be correct, as the Friends results illustrate.…”

Does sunitinib still have a place in the current recommendations for the systemic treatment of advanced renal cell carcinoma?

“…в РКИ соответственно). Авторы заключили, что эффективность сунитиниба, продемонстрированная в РКИ, подтверждается рутинной практикой [23].…”