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(s): Motzer RJ(1), Barrios CH(2), Kim TM(2), Falcon S(2), Cosgriff T(2), Harker WG(2),
Srimuninnimit V(2), Pittman K(2), Sabbatini R(2), Rha SY(2), Flaig TW(2), Page
R(2), Bavbek S(2), Beck JT(2), Patel P(2), Cheung FY(2), Yadav S(2), Schiff
EM(2), Wang X(2), Niolat J(2), Sellami D(2), Anak O(2), Knox JJ(2).
Affiliation(s): 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.
Publication date & source: 2014, J Clin Oncol. , 32(25):2765-72
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.
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