Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study.
OBJECTIVE
There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) -targeted therapy.


METHODS
Baseline characteristics and outcomes on 645 patients with anti-VEGF therapy-naïve metastatic RCC were collected from three US and four Canadian cancer centers. Cox proportional hazards regression, followed by bootstrap validation, was used to identify independent prognostic factors for OS.


RESULTS
The median OS for the whole cohort was 22 months (95% CI, 20.2 to 26.5 months), and the median follow-up was 24.5 months. Overall, 396, 200, and 49 patients were treated with sunitinib, sorafenib, and bevacizumab, respectively. Four of the five adverse prognostic factors according to the Memorial Sloan-Kettering Cancer Center (MSKCC) were independent predictors of short survival: hemoglobin less than the lower limit of normal (P < .0001), corrected calcium greater than the upper limit of normal (ULN; P = .0006), Karnofsky performance status less than 80% (P < .0001), and time from diagnosis to treatment of less than 1 year (P = .01). In addition, neutrophils greater than the ULN (P < .0001) and platelets greater than the ULN (P = .01) were independent adverse prognostic factors. Patients were segregated into three risk categories: the favorable-risk group (no prognostic factors; n = 133), in which median OS (mOS) was not reached and 2-year OS (2y OS) was 75%; the intermediate-risk group (one or two prognostic factors; n = 301), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (three to six prognostic factors; n = 152), in which mOS was 8.8 months and 2y OS was 7% (log-rank P < .0001). The C-index was 0.73.


CONCLUSIONS
This model validates components of the MSKCC model with the addition of platelet and neutrophil counts and can be incorporated into patient care and into clinical trials that use VEGF-targeted agents.
Heng
Daniel Y C
DY
FRCPC, Department of Medical Oncology, Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, Canada. daniel.heng@cancerboard.ab.ca
Xie
Wanling
W
Regan
Meredith M
MM
Warren
Mark A
MA
Golshayan
Ali Reza
AR
Sahi
Chakshu
C
Eigl
Bernhard J
BJ
Ruether
J Dean
JD
Cheng
Tina
T
North
Scott
S
Venner
Peter
P
Knox
Jennifer J
JJ
Chi
Kim N
KN
Kollmannsberger
Christian
C
McDermott
David F
DF
Oh
William K
WK
Atkins
Michael B
MB
Bukowski
Ronald M
RM
Rini
Brian I
BI
Choueiri
Toni K
TK
D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000401:mortality* / Q000556:secondary*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011379:Prognosis; D011725:Pyridines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D000077157:Sorafenib; D000077210:Sunitinib; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib; D000077210:Sunitinib