Medline ® Abstract for Reference 3
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.
Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ
J Clin Oncol. 2014 Sep;32(25):2765-72. Epub 2014 Jul 21.
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 everolimusor 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.
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. firstname.lastname@example.org.