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Research Articles

Comparative effectiveness of second-line targeted therapies for metastatic renal cell carcinoma: synthesis of findings from two multi-practice chart reviews in the United States

, , , , , , , , , & show all
Pages 2343-2353 | Accepted 24 Jul 2014, Published online: 27 Aug 2014
 

Abstract

Background:

Second-line targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors (TKIs). This study compares the effectiveness of these therapies in a multi-practice chart review and synthesizes the findings with those of a similarly designed study.

Methods:

Medical oncologists/hematologists (N = 36) were recruited to review charts for patients aged ≥18 years, received a first-line TKI and initiated second-line targeted therapy in 2010 or later. The primary outcome was time from second-line initiation to treatment failure (TTF; discontinuation, physician-assessed progression, or death, whichever occurred first). TTF was compared among patients receiving second-line everolimus (EVE), temsirolimus (TEM), or TKI as a class, using a Cox proportional hazards model adjusting for type of initial TKI and response, histological subtype, performance status, and sites of metastasis. Hazard ratios (HRs) for TTF were pooled, in a meta-analysis, with previously reported HRs for progression-free survival from a chart review with a similar design.

Results:

A total of 138, 64 and 79 patients received second-line therapy with EVE, TEM or a TKI, respectively. Adjusting for baseline characteristics, EVE was associated with numerical, but not statistically significant, reductions of 28% (HR = 0.72; 95% CI [0.45–1.16]) and 26% (HR = 0.74; 95% CI [0.48–1.15]) in the hazard of TTF compared to TEM and TKI, respectively. After pooling the HRs from both studies, EVE was associated with significantly reduced hazards of TTF compared to TEM and TKI (HR = 0.73; 95% CI [0.57–0.93]; and HR = 0.75; 95% CI [0.57–0.98], respectively).

Limitations:

Limitations include retrospective analyses with possible missing or erroneous chart data, confounding of unobserved factors due to non-randomization, and limited data for axitinib during the study period.

Conclusions:

In pooled results from two independent multi-practice chart reviews of second-line mRCC treatment, EVE was associated with significantly reduced hazards of treatment failure compared to TEM and to TKIs as a class.

Transparency

Declaration of funding

Research was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

All authors participated in the design of the study and contributed to the manuscript development. J.E.S. and P.L.L. conducted analyses.

Declaration of financial/other relationships

J.E.S. and P.L.L. have disclosed that they are employees of Analysis Group Inc., a company that received funding from Novartis Pharmaceuticals Corporation to conduct this study. Z.L., X.W., and K.C. have disclosed that they are employees of Novartis Pharmaceuticals Corporation. S.K.P. has disclosed that he has been a consultant for Novartis, Pfizer, Aveo, Denelneon, and Myriad; and has spoken at Novartis, Pfizer and Medivation. N.J.V. has disclosed that he has been a consultant for Novartis, Amgen, Celgene, Medivation, Eisai, Exelixis, Roche; has spoken at Novartis, Astellas, Johnson and Johnson, Pfizer, Dendreon, Bayer/Algeta, GSK, and Veridex/Janssen; and has received research support from Novartis, Bayer, Exelixis, Progenics, Bavarian Nordic, and Viamet. D.J.G. has disclosed that he has been a consultant for Bayer, Exelixis, GSK, and Aveo as well as received grant funding from Novartis, Pfizer, GSK, Genentech, Exelixis, and BMS; and spoken at Novartis and Pfizer. E.J. has disclosed that he has been a consultant for Novartis, GSK, and Pfizer, as well as has received grant funding from Exelixis, GSK, Novartis, and Pfizer. M.K.W. and J.A.S. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Ana Bozas PhD, an employee of Analysis Group Inc., for helping with the drafting and subsequent revision of the manuscript.

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