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Ann Oncol. 2017 Jun 1;28(6):1339-1345. doi: 10.1093/annonc/mdx075.

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.

Author information

1
Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
2
PUCRS School of Medicine, Porto Alegre, Brazil.
3
Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
4
Crescent City Research Consortium, Marrero, USA.
5
Internal Medicine, Siriraj Hospital, Mahidol University, Mahidol, Thailand.
6
Medical Oncology, The Queen Elizabeth Hospital, Woodville, Australia.
7
AOU Policlinico di Modena, Modena, Italy.
8
Yonsei Cancer Center, Seoul, South Korea.
9
University of Colorado School of Medicine, Aurora.
10
The Center for Cancer and Blood Disorders, Fort Worth.
11
Highlands Oncology Group, Fayetteville, USA.
12
Department of Oncology, Queen Elizabeth Hospital, Hong Kong, China.
13
Saskatoon Cancer Center, University of Saskatchewan, Saskatoon, Canada.
14
Academic Division of Clinical Oncology, University of Nottingham, Nottingham, UK.
15
Department of Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre Lès Nancy.
16
Novartis Pharma SAS, Rueil-Malmaison, France.
17
Novartis Oncology, East Hanover.
18
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.

Abstract

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.

Patients and 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.

Clinical Trials number:

ClinicalTrials.gov identifier, NCT00903175.

KEYWORDS:

everolimus; renal cell carcinoma; sequential targeted therapy; sunitinib

PMID:
28327953
PMCID:
PMC5452072
DOI:
10.1093/annonc/mdx075
[Indexed for MEDLINE]
Free PMC Article

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