The use of third-line targeted therapy (TTT) in metastatic renal cell carcinoma (mRCC) is not well characterized and varies due to the lack of robust data to guide treatment decisions. This study examined the use of third-line therapy in a large international population.
To evaluate the use and efficacy of targeted therapy in a third-line setting.
Twenty-five international cancer centers provided consecutive data on 4824 mRCC patients who were treated with an approved targeted therapy. One thousand and twelve patients (21%) received TTT and were included in the analysis.
Patients were analyzed for overall survival (OS) and progression-free survival using Kaplan-Meier curves, and were evaluated for overall response. Cox regression analyses were used to determine the statistical association between OS and the six factors included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. Subgroup analysis was performed on patients stratified by their IMDC prognostic risk status.
Everolimus was the most prevalent third-line therapy (27.5%), but sunitinib, sorafenib, pazopanib, temsirolimus, and axitinib were all utilized in over ≥9% of patients. Patients receiving any TTT had an OS of 12.4 mo, a progression-free survival of 3.9 mo, and 61.1% of patients experienced an overall response of stable disease or better. Patients not receiving TTT had an OS of 2.1 mo. Patients with favorable- (7.2%) or intermediate-risk (65.3%) disease had the highest OS with TTT, 29.9 mo and 15.5 mo, respectively, while poor-risk (27.5%) patients survived 5.5 mo. Results are limited by the retrospective nature of the study.
TTT remains highly heterogeneous. The IMDC prognostic criteria can be used to stratify third-line patients. TTT use in favorable- and intermediate-risk patients was associated with the greatest OS.
Patients with favorable- and intermediate-prognostic criteria disease treated with third-line targeted therapy have an associated longer overall survival compared with those with poor risk disease.
European urology. 2016 Jun 15 [Epub ahead of print]
J Connor Wells, Igor Stukalin, Craig Norton, Sandy Srinivas, Jae Lyun Lee, Frede Donskov, Georg A Bjarnason, Haru Yamamoto, Benoit Beuselinck, Brian I Rini, Jennifer J Knox, Neeraj Agarwal, D Scott Ernst, Sumanta K Pal, Lori A Wood, Aristotelis Bamias, Ajjai S Alva, Ravindran Kanesvaran, Toni K Choueiri, Daniel Y C Heng
Tom Baker Cancer Center, Calgary, AB, Canada; Queen's School of Medicine, Kingston, ON, Canada., Tom Baker Cancer Center, Calgary, AB, Canada., Dana Farber Cancer Institute, Boston, MA, USA., Division of Oncology, Stanford Medical Centre, Stanford, CA, USA., Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea., Department of Oncology, Aarhus University Hospital, Aarhus, Denmark., Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada., University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium., Cleveland Clinic, Taussig Cancer Center, Cleveland, OH, USA., Department of Medical Oncology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada., University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA., London Regional Cancer Centre, London, ON, Canada., City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada., Department of Clinical Therapeutics, National and Kapodistrian University, Athens, Greece., University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA., National Cancer Centre Singapore, Singapore, Singapore., Dana Farber Cancer Institute, Boston, MA, USA., Tom Baker Cancer Center, Calgary, AB, Canada. Electronic address: .