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 Article
| Authors: | 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.; Niolat, J.; Sellami, D.; Anak, O.; Knox, J. J. |
| Article 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. Copyright © 2014 American Society of Clinical Oncology. All rights reserved. |
| Keywords: | adult; cancer survival; controlled study; aged; major clinical study; overall survival; constipation; disease course; fatigue; neutropenia; sunitinib; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; side effect; progression free survival; drug eruption; phase 2 clinical trial; anemia; nausea; randomized controlled trial; stomatitis; thrombocytopenia; vomiting; dehydration; weight reduction; creatinine; creatinine blood level; abdominal pain; arthralgia; asthenia; backache; coughing; dizziness; dyspnea; fever; hyperglycemia; pneumonia; pruritus; drug induced headache; insomnia; karnofsky performance status; multicenter study; peripheral edema; limb pain; open study; skin discoloration; hypothyroidism; gastroesophageal reflux; crossover procedure; dyspepsia; hand foot syndrome; dry skin; epistaxis; kidney metastasis; everolimus; upper respiratory tract infection; dysgeusia; decreased appetite; upper abdominal pain; cancer prognosis; noncardiac chest pain; very elderly; human; male; female; priority journal; article |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 32 |
| Issue: | 25 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2014-09-01 |
| Start Page: | 2765 |
| End Page: | 2772 |
| Language: | English |
| DOI: | 10.1200/jco.2013.54.6911 |
| PROVIDER: | scopus |
| PUBMED: | 25049330 |
| PMCID: | PMC5569681 |
| DOI/URL: | |
| Notes: | Export Date: 1 October 2014 -- Source: Scopus |
