LBA38 - Progression-free survival (PFS) by independent review and updated overall survival (OS) results from Alliance A031203 trial (CABOSUN): cabozantinib...

Date 10 September 2017
Event ESMO 2017 Congress
Session Genitourinary tumours, non-prostate
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Genitourinary Cancers
Presenter Toni Choueiri
Citation Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440
Authors T.K. Choueiri1, C. Hessel2, S. Halabi3, B. Sanford3, O. Hahn4, M.D. Michaelson5, M. Walsh6, T. Olencki7, J. Picus8, E.J. Small9, S. Dakhil10, C. Scheffold11, D.J. George12, M.J. Morris13
  • 1Genitourinary Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 2Biostatistics And Clinical Data Management, Exelixis, Inc, South San Francisco/US
  • 3Alliance Statistics And Data Center, Duke University, Durham/US
  • 4Alliance Protocol Operations Office, Alliance for Clinical Trials in Oncology, Chicago/US
  • 5Genitourinary Cancer Center, Massachusetts General Hospital, Boston/US
  • 6Genitourinary Oncology, Dana-Farber Cancer Institute, Boston/US
  • 7Internal Medicine, Ohio State University Comprehensive Cancer Center, Columbus/US
  • 8Siteman Cancer Center, Washington University School of Medicine, St Louis/US
  • 9Hellen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco/US
  • 10School Of Medicine, University of Kansas Wichita, Wichita/US
  • 11Clinical Development, Exelixis, Inc, South San Francisco/US
  • 12Duke Cancer Institute, Duke University Medical Center, 27710 - Durham/US
  • 13Medical Oncology, Memorial Sloan Kettering Cancer Center, New York/US

Abstract

Background

Cabozantinib (Cabo), an oral, potent inhibitor of MET, AXL, and VEGFR2, improved investigator-assessed PFS (primary endpoint) compared with sunitinib (Sun) as initial targeted therapy in pts with mRCC of poor or intermediate risk (Choueiri, JCO 2016). Median PFS per investigator was 8.2 months (mo) vs 5.6 mo (HR 0.66, 95% CI 0.46 to 0.95; one-sided p = 0.012) for Cabo vs Sun.

Methods

Eligible pts had untreated clear-cell mRCC, ECOG performance status 0-2, and poor or intermediate risk disease per the International mRCC Database Consortium (IMDC) criteria (Heng, JCO 2009). 157 pts were randomized 1:1 to receive Cabo (60 mg QD) or Sun (50 mg QD, 4 weeks on/2 weeks off), stratified by IMDC risk group and the presence of bone metastases (yes vs no). We present PFS analyses per blinded independent radiology committee (IRC), subset analyses by stratification factors and MET expression based on immunohistochemistry (IHC), and an update of OS with a data cutoff of July 1, 2017.

Results

Radiographic images for 156 of 157 enrolled pts were available for assessment by the IRC. PFS per IRC was significantly increased for Cabo compared with Sun (median of 8.6 vs 5.3 mo; HR 0.48, 95% CI 0.31 to 0.74; two-sided p = 0.0008). Subgroup analyses of PFS per IRC based on the stratification factors and tumor MET levels were consistent with results for the overall population. Updated OS analysis with a median follow-up of 30.8 mo and a total of 90 deaths showed a median OS of 26.6 mo for Cabo vs 21.2 mo for Sun (HR 0.79, 95% CI 0.53 to 1.2; two-sided p = 0.27). Safety profiles were consistent with those previously reported. The incidence of all-causality grade 3 or 4 AEs was 68% with Cabo and 65% with Sun. Discontinuations due to AEs occurred for 16 pts in each treatment arm.

Conclusions

Cabo significantly increased PFS per IRC compared with Sun as initial targeted therapy in pts with mRCC. Subgroup analyses were consistent with the overall population results. Previously reported results for PFS per investigator were consistent with results reported here.

Clinical trial identification

NCT01835158

Legal entity responsible for the study

Alliance for Clinical Trials in Oncology

Funding

NCI, CTEP, Alliance

Disclosure

T.K. Choueiri: Consulting/Advisory: Pfizer, Bayer, Novartis, Merck, BMS, Genentech, Eisai, Prometheus, Cerulean, AstraZeneca, Peloton, Exelixis; Research Funding (Inst): Pfizer, Novartis, Merck, Exelixis, Tracon, BMS, AstraZeneca, Peloton, Genentech, Celldex, Takeda. C. Hessel, C. Scheffold: Employment/Stock Ownership: Exelixis. S. Halabi: Consulting/Advisory: Bayer, Genentech. O. Hahn: Honoraria: Cardinal Health (relative), Via Oncology; Advisory: Pfizer. M.D. Michaelson: Employment: Jounce Therapeutics (relative); Consulting/Advisory: Novartis, Medivation, Pfizer, Exelixis, Eisai; Research Funding (Inst): Pfizer, Eisai, Argos Therapeutics, Millennium, Novartis, Tracon. T. Olencki: Research Funding (Inst): BMS, Pfizer, Tracon. J. Picus: Consulting/Advisory: Novo Nordisk; Research Funding: Novartis, Bioclin, Altor BioScience, Agensys, Oncogenex, Mirati Therapeutics, Astex. E.J. Small: Stock Ownership: Fortis Therapeutics, Harpoon Therapeutics; Consulting/Advisory: Gilead, Dendreon. D.J. George: Consulting/Advisory/Research Funding: Exelixis, Novartis, Pfizer, GSK, Astellas, Innocrin, Genentech, BMS; Consulting/Advisory: Bayer, Dendreon, Medivation, BIND, Sanofi, Progenics, Clovis, Merck; Research Funding: Janssen, Progenics, Astellas, Millennium M.J. Morris: Consulting/Advisory: Bayer, Millennium Pharmaceuticals, Progenics: Research Funding (Inst): Bayer, Sanofi, Janssen, Endocyte All other authors have declared no conflicts of interest.