Subgroup analyses of METEOR, a randomized phase 3 trial of cabozantinib versus everolimus in patients (pts) with advanced renal cell carcinoma (RCC).

Genitourinary Cancer
Session Type and Session Title: 
Poster Session C: Renal Cell Cancer
General Session 9: Clear and Non–Clear Cell Renal Cancer
Abstract Number: 


Poster Board Number: 
Poster Session C Board #D4
J Clin Oncol 34, 2016 (suppl 2S; abstr 499)
Bernard J. Escudier, Robert J. Motzer, Thomas Powles, Nizar M. Tannir, Ian D. Davis, Frede Donskov, Viktor Grünwald, Daniel Yick Chin Heng, Thomas Hutson, Bohuslav Melichar, Dimitry Nosov, Brian I. Rini, Pamela Salman, Cora N. Sternberg, Cezary Szczylik, Pascal Wolter, Alan M Arroyo, Milan Mangeshkar, Neeraj Agarwal, Toni K. Choueiri; Institut Gustave Roussy, Villejuif, France; Memorial Sloan Kettering Cancer Center, New York, NY; Barts Cancer Institute, Barts Health, and The Royal Free London NHS Foundation Trust, London, United Kingdom; The University of Texas MD Anderson Cancer Center, Houston, TX; Monash University Eastern Health Clinical School, Box Hill, Australia; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany; Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada; Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas, TX; Onkologicka Klinika, Lekarska Fakulta Univerzity Palackeho a Fakultni Nemocnice, Olomouc, Czech Republic; N.N. Blokhin Oncology Research Center, Moscow, Russia; Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Fundación Arturo López Pérez, Santiago, Chile; San Camillo Forlanini Hospitals, Rome, Italy; Department of Oncology, Military Institute of Medicine, Warsaw, Poland; University Hospitals Leuven, Department of General Medical Oncology, Leuven, Belgium; Exelixis, South San Francisco, CA; Exelixis, Inc, South San Francisco, CA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Dana-Farber Cancer Institute, Boston, MA

Abstract Disclosures


Background: Cabozantinib (C) inhibits tyrosine kinases including VEGFRs, MET, and AXL. The METEOR phase 3 trial (NCT01865747) met its primary endpoint of significant improvement in PFS with C versus everolimus (E) in pts with advanced clear cell RCC and prior exposure to VEGFR TKIs (7.4 mo median PFS [C] vs 3.8 mo [E], HR = 0.58, 95% CI, 0.45 to 0.75; p < 0.001). The improvement in PFS was accompanied by a significant improvement in ORR and a trend for improved OS at an interim analysis. Safety profiles of C and E in this trial were similar to prior experience with each drug in this pt population. This analysis further evaluates PFS and ORR across pt subgroups. Methods: Pts had advanced RCC with clear cell component, measurable disease per RECIST 1.1, KPS ≥ 70%, and were stratified by MSKCC prognostic criteria and number of prior VEGFR TKIs. Pts must have progressed during treatment or within 6 months of the last dose of their most recent VEGFR TKI. 658 pts were randomized 1:1 to receive C (60 mg QD) or E (10 mg QD). The primary endpoint was PFS among the first 375 pts randomized. ORR was a secondary endpoint. Results: In the PFS group, 187 pts were randomized to C and 188 to E. 73% pts had 1 and 27% pts ≥ 2 prior VEGFR TKIs; 43% pts had favorable, 41% intermediate, and 15% poor risk by MSKCC criteria. Across multiple subgroups defined by baseline characteristics, PFS HRs favored C over E. PFS HRs were similar for subgroups defined by prior number of TKIs (HR = 0.56 [1 prior] and 0.67 [ ≥ 2 prior]), and showed higher activity of C over E in pts with fewer MSKCC risk factors (HR = 0.54 [0 factors], 0.56 [1 factor], 0.84 [ ≥ 2 factors]) or with metastases in various organs (HR = 0.47 [lung mets], 0.53 [liver mets], 0.50 [bone mets]). Detailed analysis of the clinical activity of C and E (PFS and ORR) across pt subgroups will be presented, including treatment duration with first VEGFR TKI ( < or ≥ 6mo), receipt of prior anti-PD1/PDL1 agents, time to progression after most recent TKI ( < or ≥ 3mo), and frequency/location of metastases. Conclusions: The METEOR trial met its primary endpoint of improved PFS, and subgroup analyses of the endpoints PFS and ORR generally favored C over E in patients with advanced RCC. Clinical trial information: NCT01865747