Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC.
BACKGROUND
RECORD-3 compared everolimus and sunitinib as first-line therapy, and the sequence of everolimus followed by sunitinib at progression compared with the opposite (standard) sequence in patients with metastatic renal cell carcinoma (mRCC). This final overall survival (OS) analysis evaluated mature data for secondary end points.


METHODS
Patients received either first-line everolimus followed by second-line sunitinib at progression (n = 238) or first-line sunitinib followed by second-line everolimus (n = 233). Secondary end points were combined first- and second-line progression-free survival (PFS), OS, and safety. The impacts of neutrophil lymphocyte ratio (NLR) and baseline levels of soluble biomarkers on OS were explored.


RESULTS
At final analysis, median duration of exposure was 5.6 months for everolimus and 8.3 months for sunitinib. Median combined PFS was 21.7 months [95% confidence interval (CI) 15.1-26.7] with everolimus-sunitinib and 22.2 months (95% CI 16.0-29.8) with sunitinib-everolimus [hazard ratio (HR)EVE-SUN/SUN-EVE, 1.2; 95% CI 0.9-1.6]. Median OS was 22.4 months (95% CI 18.6-33.3) for everolimus-sunitinib and 29.5 months (95% CI 22.8-33.1) for sunitinib-everolimus (HREVE-SUN/SUN-EVE, 1.1; 95% CI 0.9-1.4). The rates of grade 3 and 4 adverse events suspected to be related to second-line therapy were 47% with everolimus and 57% with sunitinib. Higher NLR and 12 soluble biomarker levels were identified as prognostic markers for poor OS with the association being largely independent of treatment sequences.


CONCLUSIONS
Results of this final OS analysis support the sequence of sunitinib followed by everolimus at progression in patients with mRCC. The safety profiles of everolimus and sunitinib were consistent with those previously reported, and there were no unexpected safety signals.


BACKGROUND
ClinicalTrials.gov identifier, NCT00903175.
Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
J J
JJ
Knox
PUCRS School of Medicine, Porto Alegre, Brazil.
C H
CH
Barrios
Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
T M
TM
Kim
Crescent City Research Consortium, Marrero, USA.
T
T
Cosgriff
Internal Medicine, Siriraj Hospital, Mahidol University, Mahidol, Thailand.
V
V
Srimuninnimit
Medical Oncology, The Queen Elizabeth Hospital, Woodville, Australia.
K
K
Pittman
AOU Policlinico di Modena, Modena, Italy.
R
R
Sabbatini
Yonsei Cancer Center, Seoul, South Korea.
S Y
SY
Rha
University of Colorado School of Medicine, Aurora.
T W
TW
Flaig
The Center for Cancer and Blood Disorders, Fort Worth.
R D
RD
Page
Highlands Oncology Group, Fayetteville, USA.
J T
JT
Beck
Department of Oncology, Queen Elizabeth Hospital, Hong Kong, China.
F
F
Cheung
Saskatoon Cancer Center, University of Saskatchewan, Saskatoon, Canada.
S
S
Yadav
Academic Division of Clinical Oncology, University of Nottingham, Nottingham, UK.
P
P
Patel
Department of Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre Lès Nancy.
L
L
Geoffrois
Novartis Pharma SAS, Rueil-Malmaison, France.
J
J
Niolat
Novartis Oncology, East Hanover.
N
N
Berkowitz
Novartis Oncology, East Hanover.
M
M
Marker
Novartis Oncology, East Hanover.
D
D
Chen
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
R J
RJ
Motzer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018592:Cross-Over Studies; D000068338:Everolimus / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011758:Pyrroles / Q000008:administration & dosage; D000077210:Sunitinib; D016019:Survival Analysis; D055815:Young Adult
D007211:Indoles; D011758:Pyrroles; D000068338:Everolimus; D000077210:Sunitinib
everolimus; renal cell carcinoma; sequential targeted therapy; sunitinib