814P - Efficacy of cabozantinib (cabo) vs everolimus (eve) by metastatic site and tumor burden in patients (pts) with advanced renal cell carcinoma (RCC)...

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Renal Cell Cancer
Presenter Thomas Powles
Citation Annals of Oncology (2016) 27 (6): 266-295. 10.1093/annonc/mdw373
Authors T.B. Powles1, B. Escudier2, P. de Souza3, S. Chowdhury4, D. Pook5, U. Harmenberg6, N. Basappa7, D. Geynisman8, J. Merchan9, B.G. Redman10, C. Ryan11, O. Goodman12, T. Ho13, P. Singh14, J. Lougheed15, M. Patel16, J.J. Knox17, R.J. Motzer18, T.K. Choueiri19
  • 1Department Of Medical Oncology, Barts Cancer Institute-Queen Mary University of London, EC1M 6BQ - London/GB
  • 2Medical Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 3Medical Oncology, St George Hospital Cancer Care Centre, Kogarah/AU
  • 4Oncology, Guy's and St. Thomas' Hospital NHS Trust, SE1 9RT - London/GB
  • 5Medical Oncology, Monash Cancer Centre, Bentleigh East/AU
  • 6Oncology, Karolinska University Hospital-Radiumhemmet, Stockholm/SE
  • 7Medical Oncology, University of Alberta Cross Cancer Institute, Edmonton/CA
  • 8Medical Oncology, Fox Chase Cancer Center, Philadelphia/US
  • 9Medical Oncology, University of Miami Sylvester Comprehensive Cancer Center, Miami/US
  • 10Hematology And Oncology, University of Michigan, Ann Arbor/US
  • 11Medicine/hematology Oncology, Oregon Health Science University, Portland/US
  • 12Hematology And Medical Oncology, US Oncology Research c/o Comprehensive Cancer Crts of NV, Las Vegas/US
  • 13Hematology And Oncology, Mayo Clinic Arizona, Phoenix/US
  • 14Hematology And Medical Oncology, University of Arizona, Tucson/US
  • 15Medical Affairs, Exelixis, Inc, South San Francisco/US
  • 16Regulatory Affairs, Exelixis, Inc, South San Francisco/US
  • 17Medical Oncology And Hematology, Princess Margaret Hospital, Toronto/CA
  • 18Medical Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 19Medical Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US

Abstract

Background

High tumor burden (TB) in pts with RCC is associated with poor prognosis (Iacovelli BJU Int 2012). In the Phase 3 METEOR trial (NCT01865747) in advanced RCC after prior vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) therapy (Choueiri NEJM 2015/ASCO 2016 abstr 4506), cabo significantly improved progression-free survival (PFS; HR 0.58, 95% CI 0.45–0.74; P 

Methods

658 pts were randomized 1:1 to cabo (60 mg qd) or eve (10 mg qd). Stratification factors were MSKCC risk group and number of prior VEGFR TKIs. Endpoints included PFS, OS and ORR. Subgroup analyses by metastatic site and low and high TB (< median and ≥ median sum of target lesion diameters [SoD] at baseline) are presented.

Results

At baseline, 74% of pts had visceral (lung or liver) metastases (mets); 63% had lung mets and 29% had liver mets. Median SoD at baseline was 65 mm (range 0–291) in the cabo arm and 65 mm (0–258) in the eve arm. Subgroups by metastatic site and TB generally had similar baseline characteristics on both arms. High compared to low TB was associated with fewer favorable (34% vs 57%) and more intermediate (47% vs 36%) and poor risk (19% vs 7%) pts per MSKCC criteria. For pts with visceral mets, the HRs favored cabo (PFS HR 0.48, 95% CI 0.38–0.60; OS HR 0.66, 95% CI 0.52–0.85). These benefits with cabo were consistent across the metastatic sites analyzed (liver and lung). For pts with low TB, HRs for cabo vs eve were 0.63 (95% CI 0.47–0.84) for PFS and 0.76 (95% CI 0.54–1.08) for OS vs 0.41 (95% CI 0.31–0.54) for PFS and 0.60 (95% CI 0.45–0.80) for OS for pts with high TB. Median OS with cabo was 22.0 mo for low TB and 18.1 mo for high TB pts vs 19.3 mo and 12.2 mo with eve, respectively. The most common grade 3 or 4 adverse events in these subgroups were consistent with the safety profile in the overall study population.

Conclusions

Treatment with cabo was associated with improved PFS and OS compared to eve in pts irrespective of tumor burden or metastatic sites. Pts with high tumor burden appeared to have a stronger relative benefit with cabo compared to eve for both OS and PFS.

Clinical trial identification

NCT01865747

Legal entity responsible for the study

Exelixis, Inc

Funding

Exelixis, Inc

Disclosure

T.B. Powles: Honoraria- Roche, Genentech, Novartis Consulting/Advisory- Roche, Genentech, Bristol Meyers Squibb Research Funding- AZ/Medimmune, Roche, Genentech, GlaxoSmithKline B. Escudier: Honoraria- Exelixis, Novartis, Pfizer, BMS, Roche. S. Chowdhury: Membership on an advisory board or board of directors: Sanofi, Astellas, Novartis, Janssen, Bayer, Essa, Pfizer, Clovis, Corporate-sponsored research or other substantive relationships:Sanofi, Astellas. D. Pook: Travel, Accommodations, Expenses - Astellas, Pfizer, Novartis. U. Harmenberg: Leadership- Medivir, Oncopeptides, Glionova Stock Ownership-Medivir, Ahihion. N. Basappa: Honoraria -Astellas, Janssen, Pfizer, Novartis, BMS Consulting Role- Research Funding - Lilly, Agensys, Amgen, Bayer, BI. D. Geynisman: Consulting and Advisory Role- Pfizer, Novartis, Prometheus Research Funding - Pfizer J. Merchan: Research Funding - Exelixis, Agensys, Rexaham, Eli Lilly. C. Ryan: Research Funding- Janssen, MabVax, Morphotek, OSI, Threshold, Argos, BMS, CytRx, Eisai, Exelixis, GSK, Consulting and Advisory Role- Karyopharm, EMD-Serono, Eisai, Pfizer, Onyx, Janssen O. Goodman: Honoraria - Medivation Consultancy/Advisory Role- Medivation, Exelixis Speakers Bureau – Medivation. P. Singh: Consulting and Advisory Role- Prometheus, Genentech Speakers' Bureau - Genentech J. Lougheed, M. Patel: Employment and Stock – Exelixis. J.J. Knox: Research Funding - Pfizer, Astra Zeneca Consulting and Advisory Role – Cellgene. R.J. Motzer: Consulting Advisory Role- Exelixis, Novartis, Eisai, Inc Research Funding- Exelixis, BMS, Novartis, Pfizer, Genentech, 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.