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J Clin Oncol. 2014 Sep 1;32(25):2765-72. doi: 10.1200/JCO.2013.54.6911. Epub 2014 Jul 21.

Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma.

Author information

1
Robert J. Motzer, Memorial Sloan-Kettering Cancer Center, New York, NY; Carlos H. Barrios, PUCRS School of Medicine, Porto Alegre, Brazil; Tae Min Kim, Seoul National University Hospital; and Sun Young Rha, Severance Hospital, Yonsei Cancer Center, Seoul, Korea; Silvia Falcon, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru; Thomas Cosgriff, Hematology and Oncology Specialists, Metairie, LA; Graydon Harker, Utah Cancer Specialists, Salt Lake City, UT; Vichien Srimuninnimit, Siriraj Hospital, Mahidol, Thailand; Ken Pittman, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; Roberto Sabbatini, Azienda Ospedaliero Universitaria Policlinico di Modena, Italy; Thomas W. Flaig, University of Colorado Cancer Center, Aurora, CO; Ray Page, Center for Cancer and Blood Disorders, Fort Worth, TX; Sevil E. Bavbek, American Hospital, Istanbul, Turkey; J. Thaddeus Beck, Highlands Oncology Group, Fayetteville, AR; Poulam Patel, University of Nottingham, United Kingdom; Foon-yiu Cheung, Queen Elizabeth Hospital, Kowloon, Hong Kong; Sunil Yadav, Saskatoon Cancer Centre, Saskatoon, Saskatchewan; and Jennifer J. Knox, Princess Margaret Cancer Center, University of Toronto, Toronto, Ontario, Canada; Edward M. Schiff, Dalila Sellami, and Xufang Wang, Novartis Oncology, East Hanover, NJ; Julie Niolat, Novartis Pharma SAS, Rueil-Malmaison, France; and Oezlem Anak, Novartis Pharma AG, Basel, Switzerland. motzerr@mskcc.org.
2
Robert J. Motzer, Memorial Sloan-Kettering Cancer Center, New York, NY; Carlos H. Barrios, PUCRS School of Medicine, Porto Alegre, Brazil; Tae Min Kim, Seoul National University Hospital; and Sun Young Rha, Severance Hospital, Yonsei Cancer Center, Seoul, Korea; Silvia Falcon, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru; Thomas Cosgriff, Hematology and Oncology Specialists, Metairie, LA; Graydon Harker, Utah Cancer Specialists, Salt Lake City, UT; Vichien Srimuninnimit, Siriraj Hospital, Mahidol, Thailand; Ken Pittman, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; Roberto Sabbatini, Azienda Ospedaliero Universitaria Policlinico di Modena, Italy; Thomas W. Flaig, University of Colorado Cancer Center, Aurora, CO; Ray Page, Center for Cancer and Blood Disorders, Fort Worth, TX; Sevil E. Bavbek, American Hospital, Istanbul, Turkey; J. Thaddeus Beck, Highlands Oncology Group, Fayetteville, AR; Poulam Patel, University of Nottingham, United Kingdom; Foon-yiu Cheung, Queen Elizabeth Hospital, Kowloon, Hong Kong; Sunil Yadav, Saskatoon Cancer Centre, Saskatoon, Saskatchewan; and Jennifer J. Knox, Princess Margaret Cancer Center, University of Toronto, Toronto, Ontario, Canada; Edward M. Schiff, Dalila Sellami, and Xufang Wang, Novartis Oncology, East Hanover, NJ; Julie Niolat, Novartis Pharma SAS, Rueil-Malmaison, France; and Oezlem Anak, Novartis Pharma AG, Basel, Switzerland.

Abstract

PURPOSE:

A multicenter, randomized phase II trial, RECORD-3, was conducted to compare first-line everolimus followed by sunitinib at progression with the standard sequence of first-line sunitinib followed by everolimus in patients with metastatic renal cell carcinoma.

PATIENTS AND METHODS:

RECORD-3 used a crossover treatment design. The primary objective was to assess progression-free survival (PFS) noninferiority of first-line everolimus compared with first-line sunitinib. Secondary end points included combined PFS for each sequence, overall survival (OS), and safety.

RESULTS:

Of 471 enrolled patients, 238 were randomly assigned to first-line everolimus followed by sunitinib, and 233 were randomly assigned to first-line sunitinib followed by everolimus. The primary end point was not met; the median PFS was 7.9 months for first-line everolimus and 10.7 months for first-line sunitinib (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.8). Among patients who discontinued first-line, 108 (45%) crossed over from everolimus to second-line sunitinib, and 99 (43%) crossed over from sunitinib to second-line everolimus. The median combined PFS was 21.1 months for sequential everolimus then sunitinib and was 25.8 months for sequential sunitinib then everolimus (HR, 1.3; 95% CI, 0.9 to 1.7). The median OS was 22.4 months for sequential everolimus and then sunitinib and 32.0 months for sequential sunitinib and then everolimus (HR, 1.2; 95% CI, 0.9 to 1.6). Common treatment-emergent adverse events during first-line everolimus or sunitinib were stomatitis (53% and 57%, respectively), fatigue (45% and 51%, respectively), and diarrhea (38% and 57%, respectively).

CONCLUSION:

Everolimus did not demonstrate noninferiority compared with sunitinib as a first-line therapy. The trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00903175.

PMID:
25049330
PMCID:
PMC5569681
DOI:
10.1200/JCO.2013.54.6911
[Indexed for MEDLINE]
Free PMC Article

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