LBA30_PR - CABOzantinib versus SUNitinib (CABOSUN) as initial targeted therapy for patients with metastatic renal cell carcinoma (mRCC) of poor and intermedia...

Date 10 October 2016
Event ESMO 2016 Congress
Session Presidential Symposium 3
Topics Cytotoxic agents
Renal Cell Cancer
Therapy
Biological therapy
Presenter Toni Choueiri
Citation Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435
Authors T.K. Choueiri1, S. Halabi2, B. Sanford2, O. Hahn3, M..D. Michaelson4, M. Walsh1, T. Olencki5, J. Picus6, E.J. Small7, S. Dakhil8, D. George9, M.J. Morris10
  • 1Kidney Cancer Center, Dana-Farber Cancer Institute, MA 02215 - Boston/US
  • 2Biostatistics & Bioinformatics, Duke University, 27710 - Durham/US
  • 3Medical Oncology, The University of Chicago Medical Centre, 60637 - Chicago/US
  • 4Medical Oncology, Massachusetts General Hospital, Boston/US
  • 5Medical Oncology, Ohio State Univ Medical Center, 43210 - Columbus/US
  • 6Medical Oncology, Washington University School of Medicine, 63110 - St Louis/US
  • 7Medical Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco/US
  • 8Hematology, Cancer Center of Kansas, Wichita/US
  • 9Medical Oncology, Duke University, 27710 - Durham/US
  • 10Medical Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York, NY/US

Abstract

Background

Cabozantinib (Cabo) is an oral, potent inhibitor of MET, AXL and VEGFR2 that increases progression free-survival (PFS) and overall survival (OS) in mRCC patients (pts) after VEGF-targeted therapy. This randomized phase II multicenter trial compared the PFS of Cabo to Sunitinib (Sun) as front-line targeted therapy in pts with mRCC.

Methods

Eligible pts had untreated clear-cell mRCC, ECOG performance status 0-2, and were intermediate or poor risk, per the International mRCC Database Consortium Criteria (IMDC, Heng JCO 2009). Pts were randomized 1:1 to Cabo (60 mg QD) or Sun (50 mg QD, 4 weeks on/2 weeks off). Pts were stratified by IMDC risk groups (intermediate vs. poor risk) and bone metastasis (yes, no). With 123 events (progression or deaths), the log-rank statistic has 85% power to detect a hazard ratio of 0.67 for PFS assuming a one-sided type I error of 0.12.

Results

From July 2013 to April 2015, 157 pts were randomized (79 to Cabo and 78 to Sun). Median follow up was 20.8 months (mo). 13 (16.46%) pts remained on therapy in the Cabo arm vs. 2 (2.56%) pts in the Sun arm. 80.9% of pts were IMDC intermediate risk and 36.3% had bone metastases and were equally distributed across arms. Median PFS was significantly increased at 8.2 mo (95% CI = 6.2-8.8) for Cabo vs. 5.6 mo (95% CI = 3.4-8.2) for Sun, with 31% reduction in rate of progression or death (adjusted HR 0.69, 95% CI 0.48 to 0.98, one-sided P = 0.012). ORR was 46% (95% CI 34-57%) for Cabo vs. 18% (95% CI 10-28%) for Sun. Median OS was 26.4 mo. for Cabo vs. 23.5 mo for Sun (adjusted HR 0.87, 95% CI 0.55-1.4). All-causality grade 3 or higher adverse events were 70.5% for Cabo and for 72.2% for Sun, and included diarrhea (Cabo 10%, Sun 11%), fatigue (Cabo 6%, Sun 15%), hypertension (Cabo 28%, Sun 22%), palmar-plantar erythrodysesthesia (Cabo 8%, Sun 4%) and hematological (Cabo 2.6%, Sun 22.2%). In each arm, 16 pts ended treatment due to toxicity.

Conclusions

Cabozantinib demonstrated a significant benefit in PFS and ORR over standard sunitinib in untreated intermediate and poor risk mRCC pts.

Clinical trial identification

NCT01835158

Legal entity responsible for the study

Alliance/CTEP

Funding

Exelixis

Disclosure

T.K. Choueiri: Institutional funds from Exelixis and Pfizer. Advisory board compensation from Pfizer. All other authors have declared no conflicts of interest.