First-line Mammalian target of rapamycin inhibition in metastatic renal cell carcinoma: an analysis of practice patterns from the International Metastatic Renal Cell Carcinoma Database Consortium.
BACKGROUND
Approval of the mTOR inhibitors for the treatment of mRCC was based on efficacy in poor-risk patients in the first-line setting for temsirolimus and in vascular endothelial growth factor inhibitor-refractory patients for everolimus. We strove to characterize temsirolimus and everolimus use and effectiveness in the first-line setting.


METHODS
We performed a retrospective database analysis of mRCC patients who received mTOR inhibitors as first-line targeted therapy. The Kaplan-Meier product-limit method was used to estimate the distribution of progression-free survival (PFS) and overall survival (OS).


RESULTS
We identified 127 mRCC patients who had received a first-line mTOR inhibitor. Temsirolimus was administered in 93 patients (73%) and everolimus in 34 patients (27%). The main reasons for choice of temsirolimus were poor-risk disease (38%), non-clear cell histology (27%), and clinical trial availability (15%), whereas clinical trial (82%) and non-clear cell histology (6%) drove everolimus selection. Of the temsirolimus and everolimus patients, 58% and 32% were poor-risk according to the International mRCC Database Consortium criteria, respectively. The median PFS and OS were 3.4 and 12.5 months and 4.8 and 15.9 months with temsirolimus and everolimus, respectively. Although limited by small numbers, this study characterizes a real-world, international experience with the use of mTOR inhibition in treatment-naive mRCC patients.


CONCLUSIONS
Poor-risk RCC, non-clear cell histology, and clinical trials were the predominant reasons for mTOR inhibitor selection in the front-line setting. Because of the different patient populations in which they were administered, direct comparisons of the front-line efficacy of temsirolimus and everolimus cannot be made.
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Stanford Cancer Institute, Stanford, CA. Electronic address: LaurenC_Harshman@dfci.harvard.edu.
Lauren C
LC
Harshman
Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Nils
N
Kroeger
Yonsei Cancer Center/Yonsei University College of Medicine, Seoul, South Korea.
Sun Young
SY
Rha
Aarhus University Hospital, Aarhus, Denmark.
Frede
F
Donskov
Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
Lori
L
Wood
University of Utah, Huntsman Cancer Institute, Salt Lake City, UT.
Srinivas K
SK
Tantravahi
Karmanos Cancer Institute, Wayne State University, Detroit, MI.
Ulka
U
Vaishampayan
Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
Brian I
BI
Rini
Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Jennifer
J
Knox
Cross Cancer Institute, Edmonton, Alberta, Canada.
Scott
S
North
London Regional Cancer Program, London, Ontario, Canada.
Scott
S
Ernst
The Cancer Institute Hospital of JFCR, Tokyo, Japan.
Takeshi
T
Yuasa
Stanford Cancer Institute, Stanford, CA.
Sandy
S
Srinivas
City of Hope, Duarte, CA.
Sumanta
S
Pal
Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Daniel Y
DY
Heng
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Toni K
TK
Choueiri
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D016208:Databases, Factual; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010818:Practice Patterns, Physicians'; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
Everolimus; Targeted therapy; Temsirolimus; Treatment-naive; mTOR inhibitor