Date of Award

January 2015

Document Type


Degree Name

Medical Doctor (MD)



First Advisor

Simon P. Kim

Second Advisor

Toby C. Chai

Subject Area(s)



INTRODUCTION: Although most randomized controlled trials (RCT’s) commonly report progression-free survival (PFS) as the primary endpoint, it is essential to assess overall survival (OS) and quality of life (QOL) to critically evaluate comparative effectiveness of targeted therapy for metastatic renal cell carcinoma (mRCC). Thus, we performed a systematic review and meta-analysis of RCT’s that compared first-line use of targeted agents to immunotherapy or placebo for OS and QOL for mRCC.

METHODS: A search of MEDLINE, Embase, and Cochrane Library identified phase II, phase III, and RCT’s of targeted therapy agents for mRCC. The primary outcomes were OS, PFS, complete or partial response, and QOL. Generic inverse variance with fixed effects models were used to determine pooled estimates of HR for each outcome.

RESULTS: From 2,844 studies, 19 were eligible. Pooled HR’s favored targeted therapy for OS (HR = 0.81; 95% CI, 0.74 to 0.89) and PFS (HR = 0.63; 95% CI, 0.58 to 0.68) compared to placebo or immunotherapy. Although targeted therapy was associated with higher partial response rates (31.1% vs. 8.6%; p=0.05), complete response rates were similar between targeted therapy and immunotherapy or placebo. (1.5% vs. 1.1%; p=0.62). However, only ten studies reported QOL using a variety of validated measurements showing modest trends in improved QOL.

CONCLUSIONS: Targeted agents were associated with improved OS, PFS, and partial response over IFN or placebo for first-line treatment of mRCC. Only a small fraction of patients achieved a complete response with targeted therapy. While few clinical trials examined QOL, there was significant heterogeneity in the types of validated instruments used to assess QOL.


This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.