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The association of clinical outcome to first-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients

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Abstract

There are many active drugs to treat metastatic renal cell carcinoma (mRCC) patients who progress through their first-line vascular endothelial growth factor (VEGF) inhibitor. Many clinicians choose a second-line VEGF inhibitor based on the type of response to first-line VEGF inhibitor, without data supporting this practice. This study was conducted to determine the association of response to second-line VEGF inhibitor with response to first-line VEGF inhibitor. All mRCC patients in participating centers of the International mRCC Database Consortium who were treated from January 2004 through June 2011 with a second-line VEGF inhibitor after failure of a different first-line VEGF inhibitor were retrospectively identified. The primary outcome is objective response rate (ORR) and the secondary outcome is progression-free survival (PFS) in each line of therapy. Of 1,602 total database patients, 464 patients received a first- and second-line VEGF inhibitor. The ORR to first-line therapy was 22 %, and the ORR to second-line therapy was 11 %. The ORR to second-line therapy was not different among patients achieving partial response versus stable disease versus progressive disease to first-line therapy (14 % vs. 10 % vs. 11 %, respectively; chi-squared trend test p = 0.17). The median PFS on first-line VEGF-targeted therapy was 7.5 months (95 % CI, 6.6–8.1), and the median PFS on second-line VEGF inhibitor was 3.9 months (95 % CI, 3.6–4.5). There was no correlation between first-line and second-line PFS (Pearson correlation coefficient 0.025; p = 0.59). The clinical response to a second-line VEGF inhibitor is not dependent on response to the first-line VEGF-inhibitor. Further studies are needed to define clinical parameters that predict response to second-line therapy to optimize the sequence of VEGF-targeted therapy in metastatic RCC patients.

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Conflict of interest

This study received no direct or indirect industry or pharmaceutical company support. The following authors have indicated a financial interest that is relevant to this study or to the subject matter under consideration in this article (consultant or advisory role (C), Honoraria (H), research funding (R))—Brian I. Rini: Bayer/Onyx, Roche (C) and GSK, Pfizer (C, R). Lori Wood: Pfizer and Novartis (C, R). Georg A. Bjarnason: Pfizer Canada (C, H, and R), Novartis (C, H), GSK (C, H). Lauren C. Harshman: Novartis, Pfizer (C on advisory board); BMS, Genentech, Novartis (R). Ulka Vaishampayan: Pfizer, Novartis and GSK (H & R). Jennifer J. Knox: AVEO (C), Novartis (R), Pfizer (C, R), Bayer (R). Daniel Heng: Pfizer, Novartis, Bayer (C, H). All remaining authors have declared no conflicts of interest.

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Correspondence to Daniel Y. Heng.

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This study was presented at ASCO on June 7th, 2011 in Chicago, IL, USA.

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Al-Marrawi, M.Y., Rini, B.I., Harshman, L.C. et al. The association of clinical outcome to first-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients. Targ Oncol 8, 203–209 (2013). https://doi.org/10.1007/s11523-012-0252-7

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  • DOI: https://doi.org/10.1007/s11523-012-0252-7

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