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

Robert J. Motzer, Carlos H. Barrios, Tae Min Kim, Silvia Falcon, Thomas Cosgriff, W. Graydon Harker, Vichien Srimuninnimit, Ken Pittman, Roberto Sabbatini, Sun Young Rha, Thomas W. Flaig, Ray Page, Sevil Bavbek, J. Thaddeus Beck, Poulam Patel, Foon Yiu Cheung, Sunil Yadav, Edward M. Schiff, Xufang Wang, Julie NiolatDalila Sellami, Oezlem Anak, Jennifer J. Knox

Research output: Contribution to journalArticle

225 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2765-2772
Number of pages8
JournalJournal of Clinical Oncology
Volume32
Issue number25
DOIs
Publication statusPublished - 2014 Sep 1

Fingerprint

Renal Cell Carcinoma
Disease-Free Survival
Everolimus
sunitinib
Stomatitis
Survival
Therapeutics
Cross-Over Studies
Fatigue
Diarrhea

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Motzer, Robert J. ; Barrios, Carlos H. ; Kim, Tae Min ; Falcon, Silvia ; Cosgriff, Thomas ; Harker, W. Graydon ; Srimuninnimit, Vichien ; Pittman, Ken ; Sabbatini, Roberto ; Rha, Sun Young ; Flaig, Thomas W. ; Page, Ray ; Bavbek, Sevil ; Beck, J. Thaddeus ; Patel, Poulam ; Cheung, Foon Yiu ; Yadav, Sunil ; Schiff, Edward M. ; Wang, Xufang ; Niolat, Julie ; Sellami, Dalila ; Anak, Oezlem ; Knox, Jennifer J. / 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. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 25. pp. 2765-2772.
@article{de367edf14e241ae8da1594209dac5a6,
title = "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",
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.",
author = "Motzer, {Robert J.} and Barrios, {Carlos H.} and Kim, {Tae Min} and Silvia Falcon and Thomas Cosgriff and Harker, {W. Graydon} and Vichien Srimuninnimit and Ken Pittman and Roberto Sabbatini and Rha, {Sun Young} and Flaig, {Thomas W.} and Ray Page and Sevil Bavbek and Beck, {J. Thaddeus} and Poulam Patel and Cheung, {Foon Yiu} and Sunil Yadav and Schiff, {Edward M.} and Xufang Wang and Julie Niolat and Dalila Sellami and Oezlem Anak and Knox, {Jennifer J.}",
year = "2014",
month = "9",
day = "1",
doi = "10.1200/JCO.2013.54.6911",
language = "English",
volume = "32",
pages = "2765--2772",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "25",

}

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 2014, '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', Journal of Clinical Oncology, vol. 32, no. 25, pp. 2765-2772. https://doi.org/10.1200/JCO.2013.54.6911

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, Robert J.; Barrios, Carlos H.; Kim, Tae Min; Falcon, Silvia; Cosgriff, Thomas; Harker, W. Graydon; Srimuninnimit, Vichien; Pittman, Ken; Sabbatini, Roberto; Rha, Sun Young; Flaig, Thomas W.; Page, Ray; Bavbek, Sevil; Beck, J. Thaddeus; Patel, Poulam; Cheung, Foon Yiu; Yadav, Sunil; Schiff, Edward M.; Wang, Xufang; Niolat, Julie; Sellami, Dalila; Anak, Oezlem; Knox, Jennifer J.

In: Journal of Clinical Oncology, Vol. 32, No. 25, 01.09.2014, p. 2765-2772.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Motzer, Robert J.

AU - Barrios, Carlos H.

AU - Kim, Tae Min

AU - Falcon, Silvia

AU - Cosgriff, Thomas

AU - Harker, W. Graydon

AU - Srimuninnimit, Vichien

AU - Pittman, Ken

AU - Sabbatini, Roberto

AU - Rha, Sun Young

AU - Flaig, Thomas W.

AU - Page, Ray

AU - Bavbek, Sevil

AU - Beck, J. Thaddeus

AU - Patel, Poulam

AU - Cheung, Foon Yiu

AU - Yadav, Sunil

AU - Schiff, Edward M.

AU - Wang, Xufang

AU - Niolat, Julie

AU - Sellami, Dalila

AU - Anak, Oezlem

AU - Knox, Jennifer J.

PY - 2014/9/1

Y1 - 2014/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84906815674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906815674&partnerID=8YFLogxK

U2 - 10.1200/JCO.2013.54.6911

DO - 10.1200/JCO.2013.54.6911

M3 - Article

C2 - 25049330

AN - SCOPUS:84906815674

VL - 32

SP - 2765

EP - 2772

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 25

ER -