818P - Analysis of regional differences in the phase 3 METEOR study of cabozantinib (cabo) versus everolimus (eve) in advanced renal cell carcinoma (RCC)

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Renal Cell Cancer
Presenter Nizar Tannir
Citation Annals of Oncology (2016) 27 (6): 266-295. 10.1093/annonc/mdw373
Authors N. Tannir1, T. Powles2, R.J. Motzer3, F. Rolland4, G. Gravis5, M. Staehler6, M. Rink7, M. Retz8, T. Csoszi9, J. McCaffrey10, U. De Giorgi11, C. Caserta12, S. Cheporov13, E. Esteban Gonzalez14, I. Duran15, J.G. Larkin16, W. Berg17, D. Clary17, B. Escudier18, T.K. Choueiri19
  • 1Department Of Genitourinary Medical Oncology, MD Anderson Cancer Center, 77030-3721 - Houston/US
  • 2Experimental Cancer Medicine, Barts Cancer Institute-Queen Mary University of London, EC1M 6BQ - London/GB
  • 3Medical Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 4Department Of Medical Oncology, ICO Institut de Cancerologie de l'Ouest René Gauducheau, 44805 - St. Herblain/FR
  • 5Urology, Medical Outpatient, Institute Paoli Calmettes, 13273 - Marseille/FR
  • 6Klinikum Der Ludwig/urology Dept, Maximilians-Universität München, 81377 - München/DE
  • 7Department Of Urology, University Medical Center Hamburg-Eppendorf, 20246 - Hamburg/DE
  • 8Department Of Urology, Klinikum Rechts der Isar de Technische, 81675 - München/DE
  • 9Medical Oncology, Hematology, Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelőintéze, 5004 - Szolnok/HU
  • 10Oncology, Medical Oncology, Mater Private Hospital, Dublin 7 - Dublin/IE
  • 11Medical Oncology, Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumor, 47014 - Meldola/IT
  • 12Oncology Dept., Azienda Ospedaliera Sta Maria, 05100 - Terni/IT
  • 13Clinical Oncology, Regional Clinical Oncology Hospital, 150054 - Yaroslavl/RU
  • 14Oncology, Clinica, Edificio de Consultas Externas, 33011 - Oviedo/ES
  • 15Medical Oncology, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 16Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, SW3 6JJ - London/GB
  • 17Medical Affairs, Exelixis, Inc., 94080 - South San Francisco/US
  • 18Immunotherapy And Innovative Therapy Unit, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 19Department Of Genitourinary Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, 02215 - Boston/US

Abstract

Background

In the METEOR study (NCT01865747), patients (pts) with advanced RCC and prior treatment with an antiangiogenic therapy were randomized to receive cabo or eve. Improved progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were demonstrated in the cabo arm vs the eve arm (Choueiri 2016 JCO suppl abstr 4506). Baseline characteristics and clinical outcomes were evaluated in pts enrolled in three regions: Europe (EU; 19 countries), North America (NA; US, Canada) and Asia Pacific (AP; Australia, South Korea, Taiwan).

Methods

658 pts were randomized 1:1 to receive cabo (60 mg qd) or eve (10 mg qd). Stratification factors were MSKCC risk group and number of prior vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs).

Results

Of pts enrolled in METEOR, 320, 240 and 86 came from EU, NA and AP, respectively. Baseline demographic characteristics other than race were similar between regions. Pts with 2 or more prior TKIs were more frequent in EU and NA (31% and 33%) than AP (17%). Prior use of axitinib was rare in AP (1%) compared to EU and NA (17% and 22%). PFS and OS in the cabo arm were prolonged vs eve in all regions, with PFS hazard ratios (HR) of 0.54, 0.50 and 0.43 and OS HRs of 0.67, 0.79 and 0.49 for EU, NA and AP, respectively. The cabo arm ORRs (% [95% CI]) for EU, NA and AP regions were 15% (10–21), 16% (10–24) and 28% (15–45). Adverse event (AE) rates were generally similar across regions. Subsequent treatment with VEGFR-TKI and anti-PD-1/L1 agents was most frequent in NA and least frequent in AP, and at higher frequency in the eve arm versus the cabo arm. Posttrial use of eve in the cabo arm was similar across regions (Table).

Subsequent Therapies Europe Europe North America North America Asia Pacific Asia Pacific
cabo (n = 167) eve (n = 153) cabo (n = 118) eve (n = 122) cabo (n = 39) eve (n = 47)
Any VEGFR TKI, % 25 50 29 57 5 21
Axitinib, % 17 28 22 38 3 2
Sorafenib, % 4 14 3 6 0 6
Sunitinib, % 4 11 8 9 3 11
Pazopanib, % 2 8 2 7 0 4
Cabo, % 0 1 0 6 0 0
Anti-PD-1/PD-L1, % 2 2 9 13 3 0
Eve, % 30 4 28 4 33 9

Conclusions

Improvements in PFS, OS and ORR for cabo vs eve were measured across all regions in the METEOR trial despite differences in subsequent treatment. No differences in safety were reported.

Clinical trial identification

NCT01865747

Legal entity responsible for the study

Exelixis, Inc.

Funding

Exelixis, Inc.

Disclosure

N. Tannir: Honoraria: Novartis, BMS, GSK, Pfizer, Exelixis, Nektar Consulting/Advisory: Novartis, BMS, GSK, Pfizer, Exelixis, Nektar Travel, Accomodations, expenses: Novartis, BMS, GSK, Pfizer, Exelixis, Nektar Research Funding: Novartis, BMS, Exelixis, Epizyme. T. Powles: Honoraria: Roche/Genentech, Novartis Consulting or Advisory Role: Roche/Genentech, BMS Research Funding: AZ/MedImmune, Roche/Genentech, GSK. R.J. Motzer: Consulting or Advisory Role: Pfizer, Novartis, Eisai Inc. Research Funding: Exelixis, BMS, Novartis, Pfizer, Genentech/Roche. F. Rolland: Honoraria: Novartis Consulting/Advisory Role: Novartis. G. Gravis: Consulting/Advisory Role: Novartis, Pfizer. M. Staehler: Consulting/Advisory Role: Bayer, Pfizer, GSK, Novartis, BMS, Roche Speakers' Bureau: Bayer, Pfizer, GSK, Novartis, BMS, Roche Research Funding: Bayer, Pfizer, GSK, Novartis, BMS, Roche, Exelixis. U. De Giorgi: Advisory/Consulting Role: Pfizer, Novartis, Bayer. C. Caserta: Speakers' Bureau: Pfizer Travel, Accommodations and Expenses: Astellas, Merck Serona, Roche Pharma AG, Sanofi. I. Duran: Advisory/Consulting Role: Sanofi-Aventis, Bayer, BMS, Astellas, Roche/Genentech, Jansen, Pierre Fabre Research Funding: Jansen, Sanofi-Aventis Travel, Accomodations, Expenses: Astellas J.G. Larkin: Research Funding: Pfizer, Novartis, BMS, MSD. W. Berg: Employee and Stock Ownership: Exelixis, Inc. D. Clary: Employee: Exelixis, Inc. Stock Ownership: Exelixis, Inc. B. Escudier: Honoraria: Exelixis, Novartis, Pfizer, BMS, Roche. T.K. Choueiri: Consulting/Advisory Role: Pfizer, GSK, Novartis, Merck, Bayer, Eisai, Roche, Prometheus Labs Inc, BMS, Foundation Medicine Inc. Research Funding: Pfizer, GSK, Novartis, BMS, Merck, Exelixis, Roche, AstraZeneca, Tracon, Peloton. All other authors have declared no conflicts of interest.