Phase II trial of second-line everolimus in patients with metastatic renal cell carcinoma (RECORD-4) Journal Article


Authors: Motzer, R. J.; Alyasova, A.; Ye, D.; Karpenko, A.; Li, H.; Alekseev, B.; Xie, L.; Kurteva, G.; Kowalyszyn, R.; Karyakin, O.; Neron, Y.; Cosgriff, T.; Collins, L.; Brechenmacher, T.; Lin, C.; Morgan, L.; Yang, L.
Article Title: Phase II trial of second-line everolimus in patients with metastatic renal cell carcinoma (RECORD-4)
Abstract: Background: RECORD-1 demonstrated clinical benefit of everolimus in patients with metastatic renal cell carcinoma (mRCC) previously treated with sunitinib, sorafenib, or both; prior treatment with cytokines, bevacizumab, and chemotherapy was also permitted. RECORD-4 prospectively assessed everolimus in a purely second-line setting. Methods: Patients with clear-cell mRCC were enrolled into one of three cohorts based on first-line therapy with sunitinib, other anti-VEGF agents, or cytokines. Patients were treated with everolimus 10 mg/day until progression (RECIST, v1.0) or intolerance. The primary end point was progression-free survival (PFS) per investigator review. Data cutoffwas 1 September 2014, for the primary analysis and 26 June 2015, for the final overall survival (OS) analysis. Results: Enrolled patients (N ≥ 134) previously received sunitinib (n ≥ 58), other anti-VEGF therapy (n ≥ 62; sorafenib, 23; bevacizumab, 16; pazopanib, 13; tivozanib, 5; and axitinib, 3), or cytokines (n ≥ 14). Overall median age was 59 years, and most patients were men (68%) and of favorable/intermediate MSKCC risk (52/37%). Overall median PFS was 7.8 months [95% confidence interval (CI) 5.7-11.0]; in the cohorts, it was 5.7 months (95% CI 3.7-11.3) with previous sunitinib, 7.8 months (95% CI 5.7-11.0) with other previous anti-VEGF therapy, and 12.9 months [95% CI 2.6-not estimable (NE)] with previous cytokines. Overall, 67% of patients achieved stable disease as their best objective response. At final OS analysis, total median OS was 23.8 months (95% CI 17.0-NE) and, in the cohorts, it was 23.8 months (95% CI 13.7-NE) with previous sunitinib, 17.2 months (95% CI 11.9-NE) with other previous anti-VEGF therapy, and NE (95% CI 15.9-NE) with previous cytokine-based therapy. Overall, 56% of patients experienced grade 3 or 4 adverse events (regardless of relationship to study drug). Conclusions: These results confirm the PFS benefit of second-line everolimus after first-line sunitinib or other anti-VEGF therapies. The safety profile of everolimus was consistent with previous experience. Clinical trial name and identifier: Everolimus as Second-line Therapy in Metastatic Renal Cell Carcinoma (RECORD-4), ClinicalTrials.gov identifier, NCT01491672. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Keywords: prospective study; everolimus; metastatic renal cell carcinoma; second-line; sequential targeted therapy
Journal Title: Annals of Oncology
Volume: 27
Issue: 3
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2016-03-01
Start Page: 441
End Page: 448
Language: English
DOI: 10.1093/annonc/mdv612
PROVIDER: scopus
PUBMED: 26681676
PMCID: PMC5006123
DOI/URL:
Notes: Article -- Export Date: 4 April 2016 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Robert Motzer
    761 Motzer