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

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237 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

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Motzer, R. J., Barrios, C. H., Kim, T. M., Falcon, S., Cosgriff, T., Harker, W. G., Srimuninnimit, V., Pittman, K., Sabbatini, R., Rha, S. Y., Flaig, T. W., Page, R., Bavbek, S., Beck, J. T., Patel, P., Cheung, F. Y., Yadav, S., Schiff, E. M., Wang, X., ... Knox, J. J. (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, 32(25), 2765-2772. https://doi.org/10.1200/JCO.2013.54.6911