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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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| Authors: | Mhd Y Al-Marrawi Brian I Rini Lauren C Harshman Georg Bjarnason Lori Wood Ulka Vaishampayan Mary MacKenzie Jennifer J Knox Neeraj Agarwal Hulayel Al-Harbi Christian Kollmannsberger Min-Han Tan Sun Young Rha Frede N Donskov Scott North Toni K Choueiri Daniel Y Heng |
| Institution: | 1. Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH, USA 3. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute/Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA 4. Sunnybrook Odette Cancer Centre, Toronto, ON, Canada 5. Queen Elizabeth II Health Sciences Center, Halifax, NS, Canada 6. Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA 7. London Health Sciences Center, London, ON, Canada 8. Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada 9. Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA 10. University of Calgary, Calgary, AB, Canada 11. Vancouver Cancer Center, British Columbia Cancer Agency, Vancouver, BC, Canada 12. Institute of Bioengineering and Nanotechnology, National Cancer Centre Singapore, Singapore, Singapore 14. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea 15. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark 16. Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada 17. Tom Baker Cancer Centre, University of Calgary, 1331 29th St NW, Calgary, AB, T2N 4N2, Canada |
| 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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