Third-line Targeted Therapy in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.
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.
Tom Baker Cancer Center, Calgary, AB, Canada; Queen's School of Medicine, Kingston, ON, Canada.
J Connor
JC
Wells
Tom Baker Cancer Center, Calgary, AB, Canada.
Igor
I
Stukalin
Dana Farber Cancer Institute, Boston, MA, USA.
Craig
C
Norton
Division of Oncology, Stanford Medical Centre, Stanford, CA, USA.
Sandy
S
Srinivas
Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Jae Lyun
JL
Lee
Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
Frede
F
Donskov
Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.
Georg A
GA
Bjarnason
University of Texas Southwestern Medical Center, Dallas, TX, USA.
Haru
H
Yamamoto
Department of General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Benoit
B
Beuselinck
Cleveland Clinic, Taussig Cancer Center, Cleveland, OH, USA.
Brian I
BI
Rini
Department of Medical Oncology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada.
Jennifer J
JJ
Knox
University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
Neeraj
N
Agarwal
London Regional Cancer Centre, London, ON, Canada.
D Scott
DS
Ernst
City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Sumanta K
SK
Pal
Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada.
Lori A
LA
Wood
Department of Clinical Therapeutics, National and Kapodistrian University, Athens, Greece.
Aristotelis
A
Bamias
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
Ajjai S
AS
Alva
National Cancer Centre Singapore, Singapore, Singapore.
Ravindran
R
Kanesvaran
Dana Farber Cancer Institute, Boston, MA, USA.
Toni K
TK
Choueiri
Tom Baker Cancer Center, Calgary, AB, Canada. Electronic address: daniel.heng@albertahealthservices.ca.
Daniel Y C
DY
Heng
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D016208:Databases, Factual; D005260:Female; D006801:Humans; D038622:Internationality; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis
D000970:Antineoplastic Agents
Metastatic renal cell carcinoma; Targeted therapy; Third line therapy