239O - RECORD-4: Multicenter phase 2 trial of second-line everolimus (EVE) in patients (pts) with metastatic renal cell carcinoma (mRCC): Asian versus non...

Date 19 December 2015
Event ESMO Asia 2015 Congress
Session Genitourinary tumours
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Presenter Lin Yang
Citation Annals of Oncology (2015) 26 (suppl_9): 71-79. 10.1093/annonc/mdv524
Authors L. Yang1, A. Alyasova2, D. Ye3, A. Karpenko4, H. Li5, B. Alekseev6, L. Xie7, G. Kurteva8, R.D. Kowalyszyn9, O. Karyakin10, Y.V. Nerón11, T.M. Cosgriff12, L. Collins13, T. Brechenmacher14, J.C. Lin13, L. Morgan13, R. Motzer15
  • 1Medical Department Of Cancer Hospital, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), 100021 - Beijing/CN
  • 2Federal Budget Medical Institution, Prevoljskiy Region Medical Centre, Nizhny Novgorod/RU
  • 3Department Of Urological Surgery, Fudan University Shanghai Cancer Center (FUSCC), 200032 - Shanghai/CN
  • 4Surgical Department #3, Leningrad Regional Oncologic Dispensary, Saint Petersburg/RU
  • 5Department Of Urology, Peking Union Medical College Hospital, Shanghai/CN
  • 6Federal State Institution, Moscow Hertzen Oncology Institute, Moscow/RU
  • 7Department Of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhenjiang/CN
  • 8Chemotherapy Clinic, National Center of Oncology-SBALO EAD, 1756 - Sofia/BG
  • 9Centro De Investigaciones Clinicas, Clinica Viedma, 8500 - Viedma/AR
  • 10Department Of Urology, Medical Radiological Research Center RAMS, Obninsk/RU
  • 11Medical Oncology, Centro de Pesquisas Oncologicas, Florianopolis/BR
  • 12Crescent City Research Consortium, Hematology And Oncology Specialists, East Jefferson General Hospital, Metairie/US
  • 13Oncology Global Medical Affairs, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 14Biometrics Data Management, Bios, Novartis Pharma S.A.S., Rueil-Malmaison/FR
  • 15Department Of Medicine - Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York/US

Abstract

Aim/Background

RECORD-4 prospectively evaluated efficacy and safety of EVE in pts with mRCC who progressed on first-line treatment with an anti-VEGF or a cytokine agent. Here we present outcomes in Asian versus (vs) non-Asian pts.

Methods

Adult pts (≥ 18 years) with clear cell mRCC were enrolled into 1 of 3 cohorts based on prior first-line therapy: sunitinib, other anti-VEGF (sorafenib, bevacizumab, pazopanib, other), or cytokines. Pts received EVE 10 mg/d until progression of disease (RECIST, v1.0) or intolerance. The primary endpoint was PFS by investigator review. Data cutoff: Sept 1, 2014.

Results

Among Asian (n = 55) vs non-Asian (n = 79) pts, 98% vs 84% had good/intermediate MSKCC prognosis; 73% vs 65% were men, and 85% vs 73% were <65 years of age. All (100%) Asian pts were of Chinese ethnicity. Median duration of exposure was 5.5 mo for Asian and 6.0 mo for non-Asian pts. Among Asian vs non-Asian pts, median PFS (mo, 95% CI) was 7.4 (5.5-11.0) vs 7.8 (5.3-12.9) overall, 7.4 (3.7-12.8) vs 4.0 (2.5-12.9) with prior sunitinib, 5.7 (3.6-11.0) vs 9.2 (5.5-18.0) with prior other anti-VEGFs, and 16.5 (1.9-not estimable [NE]) vs 12.9 (2.6-NE) with prior cytokines. Clinical benefit rate was similar between populations: 74.5% (95% CI, 61.0-85.3) for Asian pts and 74.7% (95% CI, 63.6-83.8) for non-Asian pts. Most pts achieved stable disease as best overall response (Asian, 63.6%; non-Asian, 69.6%). Overall rate of grade 3/4 adverse events (AEs) appeared similar for Asian (58%) and non-Asian pts (54%). Most frequently reported grade 3/4 AEs (incidences ≥5% in the overall population) for Asian vs non-Asian pts were stomatitis/mouth ulceration (11% vs 5%), anemia (7% vs 17%), hypertriglyceridemia (5% vs 4%), decreased hemoglobin (5% vs 0), proteinuria (5% vs 1%), respiratory failure (5% vs 1%), and hyperglycemia (4% vs 5%).

Conclusions

Second-line EVE demonstrated comparable efficacy and AE profiles in Asian and non-Asian pts. Efficacy and safety outcomes by prior therapy should be interpreted with caution because of small pt numbers in some subpopulations.

Clinical trial identification

NCT01491672

Disclosure

A. Alyasova: consulting physician for Novartis and compensation from Novartis for consulting and research support and business travel. D. Ye: Novartis Investigator but no compensation received. B. Alekseev: research funding by Astellas, Johnson and Johnson and Novartis; compensation from Sanofi, Johnson and Johnson and Novartis for consulting or advisory role. L. Xie: clinical trial principle investigator for Ipsen Pharma Biotech. R.D. Kowalyszyn: compensation from Novartis, Eli Lilly, Glaxo Smith Kline, Roche and Elea for research funding; compensation from Merck Sharp Dohme and Novartis for consulting and speaker's bureau. O. Karyakin: employed by Medical Radiological Research Center. Y.V. Nerón: research funding from Active Biotech, Amgen, Astellas, Blau Farmacêutica, Genentech, Glaxo Smith Kline, Novartis, Roche, Tesaro. T.M. Cosgriff: Stockholder in Enanta and Alexion. Employed by Lakeside Hospice. L. Collins: A Novartis Pharmaceutical Corporation employee. T. Brechenmacher, J.C. Lin, L. Morgan: Novartis employee. R. Motzer: grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Pfizer, grants and personal fees from GlaxoSmithKline, grants from Genentech, grants from GlaxoSmithKline, outside the submitted work. All other authors have declared no conflicts of interest.