A significant subgroup of metastatic renal cell carcinoma (mRCC) patients discontinue vascular endothelial growth factor-targeted therapies (VEGF-TT) because of toxicity. Whether clinical outcomes differ in patients who receive second-line (2L) targeted therapy on the basis of reason for discontinuation of first-line (1L) therapy is unknown.
Patients from 15 International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) centers who started 2L targeted therapy were included and the reason for discontinuation of 1L therapy retrospectively collected. Treatment outcomes of 2L, including response, time to treatment failure, and overall survival (OS) were assessed.
In total, 1124 patients were identified: 866 patients (77%) discontinued 1L VEGF-TT because of disease progression, and 208 patients (19%) because of toxicity. The reason for discontinuation of 1L therapy did not differ according to IMDC risk group. Compared with patients who stopped 1L VEGF-TT because of disease progression, patients who stopped because of toxicity had greater clinical benefit (nonprogressive disease as best response) in 2L treatment (68% vs. 56%; adjusted odds ratio, 1.58; 95% confidence interval [CI], 1.07-2.35; P = .023) and longer OS (17.4 vs. 11.2 months; adjusted hazard ratio, 0.69; 95% CI, 0.56-0.84; P = .0002) adjusted for type of therapy, time to initiation of 2L treatment, IMDC risk group, and number of metastases at initiation of 2L treatment.
mRCC patients who discontinue 1L VEGF-TT because of toxicity have better outcomes with 2L therapy than patients who stop therapy because of disease progression. These findings should be taken into consideration when designing clinical trials for 2L therapies in mRCC.
Clinical genitourinary cancer. 2017 Jan 12 [Epub]
Guillermo De Velasco, Wanling Xie, Frede Donskov, Laurence Albiges, Benoit Beuselinck, Sandy Srinivas, Neeraj Agarwal, Jae Lyun Lee, James Brugarolas, Lori A Wood, Sun-Young Rha, Christian Kollmannsberger, Scott North, Ravindran Kanesvaran, Brian I Rini, Reuben Broom, Haru Yamamoto, Marina D Kaymakcalan, Daniel Y C Heng, Toni K Choueiri
Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA; Department of Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain., Deparment of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, MA., Department of Oncology, Aarhus University Hospital, Aarhus, Denmark., Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France., Department of General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven, Belgium., Division of Oncology, Stanford Medical Center, Stanford, CA., Division of Oncology, University of Utah Huntsman Cancer Institute, Salt Lake City, UT., Department of Oncology, University of Ulsan College of Medicine, Seoul, South Korea., Hematology-Oncology Division, University of Texas Southwestern Medical Center, Dallas, TX., Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada., Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea., British Columbia Cancer Agency-Vancouver Cancer Center, University of British Columbia, Vancouver, British Columbia, Canada., Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada., Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore., Department of Hematology and Oncology, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH., Department of Medical Oncology, Auckland City Hospital, Auckland, New Zealand., Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA., Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada., Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA. Electronic address: .