Phase 2 trial of second-line everolimus in patients with metastatic renal cell carcinoma (RECORD-4)

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.

Patients with clear cell mRCC were enrolled into 1 of 3 cohorts based on first-line therapy with sunitinib, other anti-VEGF agents, or cytokines. Patients were treated with everolimus 10 mg/d until progression (RECIST, v1. 0) or intolerance. The primary end point was progression-free survival (PFS) per investigator review. Data cutoff was September 1, 2014, for the primary analysis and June 26, 2015, for the final overall survival (OS) analysis.

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% 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) 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-not estimable [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).

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.

Everolimus as Second-line Therapy in Metastatic Renal Cell Carcinoma (RECORD-4), ClinicalTrials. gov identifier, NCT01491672.

Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2015 Dec 17 [Epub ahead of print]

R J Motzer, A Alyasova, D Ye, A Karpenko, H Li, B Alekseev, L Xie, G Kurteva, R Kowalyszyn, O Karyakin, Y Neron, T Cosgriff, L Collins, T Brechenmacher, C Lin, L Morgan, L Yang

Memorial Sloan Kettering Cancer Center, New York, New York, USA. , Prevoljskiy Region Medical Centre, Novgorod, Russia. , Fudan University Shanghai Cancer Center, Shanghai, China. , Leningrad Regional Oncologic Dispensary, Saint-Petersburg, Russia. , Peking Union Medical College Hospital, Beijing, China. , Moscow Hertzen Oncology Institute, Moscow, Russia. , First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, China. , Center of Oncology, Sofia, Bulgaria. , Centro de Investigaciones Clinicas Clinica Viedma, Viedma, Argentina. , Medical Radiological Research Center, Oncology Department, Obninsk, Russia. , Centro de Pesquisas Oncológicas-CEPON, Florianopolis-SC, Brazil. , Crescent City Research Consortium, Marrero, Louisiana. , Novartis Oncology, East Hanover, New Jersey, USA. , Novartis Pharma S. A. S. , Rueil-Malmaison, France. , Novartis Oncology, East Hanover, New Jersey, USA. , Novartis Oncology, East Hanover, New Jersey, USA. , Cancer Institute and Hospital, Chinese Academy of Medical Science, Beijing, China.

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