e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

Nivolumab plus cabozantinib (N+C) vs sunitinib for advanced renal cell carcinoma (aRCC): outcomes by baseline disease characteristics in the phase 3 CheckMate 9ER trial (#243)

David Pook 1 , Thomas Powles 2 , Mauricio Burotto 3 , Maria T. Bourlon 4 , James J. Hsieh 5 , Umberto Basso 6 , Amishi Y. Shah 7 , Cristina Suarez 8 , Camillo Porta 9 , Carlos Barrios 10 , Howard Gurney 11 , Elizabeth R. Kessler 12 , Margitta Retz 13 , Saby George 14 , Bernard Escudier 15 , Joshua Zhang 16 , Burcin Simsek 16 , Christian Scheffold 17 , Robert J. Motzer 18 , Toni K. Choueiri 19 , Andrea B. Apolo 20
  1. Cabrini Monash University Department of Medical Oncology, Cabrini Health, Malvern, Australia
  2. Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free National Health Service Trust, London, United Kingdom
  3. Bradford Hill Clinical Research Center, Santiago, Chile
  4. Urologic Oncology Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
  5. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States
  6. Istituto Oncologico Veneto IOV IRCCS, Padova, Italy
  7. MD Anderson Cancer Center, Houston, TX, United States
  8. Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
  9. University of Pavia, Pavia, Italy
  10. Hospital São Lucas, PUCRS, Porto Alegre, Brazil
  11. Westmead Hospital and Macquarie University, Sydney, NSW, Australia
  12. University of Colorado School of Medicine, Aurora, CO, United States
  13. Rechts der Isar Medical Center, Technical University Munich, Munich, Germany
  14. Roswell Park Cancer Institute, Buffalo, NY, United States
  15. Gustave Roussy, Villejuif, France
  16. Bristol Myers Squibb, Princeton, NJ, United States
  17. Exelixis, Inc., Alameda, CA, United States
  18. Memorial Sloan Kettering Cancer Center, New York, NY, United States
  19. Dana-Farber Cancer Institute, The Lank Center for Genitourinary Oncology, Boston, MA, United States
  20. National Cancer Institute, National Institutes of Health, Bethesda, MD, United States

Aims: First-line N+C significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs sunitinib in aRCC patients in the phase 3 CheckMate 9ER trial (NCT03141177; Choueiri NEJM 2021). Assessing outcomes of N+C vs sunitinib by baseline disease characteristics can inform clinical decision making.

Methods: Patients with clear cell aRCC were randomized to nivolumab 240 mg IV Q2W + cabozantinib 40 mg PO QD vs sunitinib 50 mg PO QD (4 weeks on/2 weeks off). In this post hoc exploratory analysis, PFS, OS, and ORR were assessed across patient subgroups: IMDC risk, number of organs with ≥1 target/nontarget lesion (T/NT), sum of diameters of target lesions (sDTL), and site of metastasis. PFS and ORR were evaluated per RECIST v1.1 by blinded independent central review.

Results: Median follow-up in ITT patients was 23.5 months. N+C was favored over sunitinib for PFS across all subgroups, median (hazard ratio [HR], 95% CI): IMDC risk favorable, 25 vs 13 months (0.58, 0.36-0.93); intermediate, 17 vs 9 months (0.58, 0.45-0.76); poor, 10 vs 4 months (0.36, 0.23-0.56); T/NT 1 organ site, 25 vs 13 months (0.53, 0.32-0.88); ≥2 organ sites, 15 vs 7 months (0.53, 0.43-0.67); sDTL <72.1mm, 20 vs 10 months (0.52, 0.39-0.71); ≥72.1mm, 11 vs 6 months (0.53, 0.40-0.70); metastases lung, 17 vs 8 months (0.51, 0.40-0.64); bone, 18 vs 4 months (0.38, 0.25-0.59); liver, 11 vs 6 months (0.51, 0.33-0.79). N+C was favored over sunitinib for ORR across all subgroups (range, 38%-66% vs 10%-44%) and for OS across most subgroups (HR range, 0.45-0.94). Complete responses were seen with N+C in all subgroups (range, 1%-20%).

Conclusions: Efficacy benefits with N+C vs sunitinib were maintained regardless of IMDC risk, metastasis site, or extent of tumor burden at baseline, supporting N+C as first-line treatment for patients with aRCC.