CABOMETYX® (cabozantinib) aRCC data in combination with OPDIVO® (nivolumab)
Treatment until disease progression or unacceptable toxicity1*
- Excluded patients with autoimmune disease or other medical conditions requiring systemic immunosuppression1
- Median follow-up was 18.1 months (range: 10.6-30.6 months) with an extended follow-up analysis at 44 months (range: 36.5-56.5 months)2,4
- 32.9-month median follow-up data (range: 25.4-45.4 months) was a pre-planned final OS analysis that occurred after observation of 271 events1,5,6
Tumor assessments were performed at baseline, after randomization at Week 12, then every 6 weeks until Week 60, and then every 12 weeks thereafter. Treatment beyond RECIST v1.1–defined disease progression was permitted if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. OPDIVO dosing was not to exceed a total of 2 years (from cycle 1).1
PFS and ORR were assessed by BICR.1
Other exploratory endpoints included biomarkers, pharmacokinetics, immunogenicity, and PFS-2.2
- IMDC risk group (favorable vs intermediate vs poor)
- PD-L1 tumor expression (≥1% vs <1% or indeterminate)
- Geographic region (United States, Canada, and Western and Northern Europe vs rest of world)§
IMDC risk distribution in CheckMate-9ER was representative of aRCC population1,3,7-9
Baseline Characteristics WERE Balanced Across Treatment Arms6
|CABOMETYX + OPDIVO
|<65||191 (59.1)||210 (64.0)|
|≥65||132 (40.9)||118 (36.0)|
|US/Canada/W Europe/N Europe§||158 (48.9)||161 (49.1)|
|Rest of world||165 (51.1)||167 (50.9)|
|Karnofsky performance status7|
|70||14 (4.3)||18 (5.5)|
|80||52 (16.1)||67 (20.4)|
|90||110 (34.1)||112 (34.1)|
|100||147 (45.5)||129 (39.3)|
|Not reported||0||2 (0.6)|
|Baseline IMDC prognostic score2|
|Favorable||74 (22.9)||72 (22.0)|
|Intermediate||188 (58.2)||188 (57.3)|
|Poor||61 (18.9)||68 (20.7)|
|Time from diagnosis to randomization7|
|<1 year||210 (65.0)||214 (65.2)|
|≥1 year||112 (34.7)||111 (33.8)|
|Not reported||1 (0.3)||3 (0.9)|
|Yes||222 (68.7)||233 (71.0)|
|No||101 (31.3)||95 (29.0)|
|Yes||46 (14.2)||45 (13.7)|
|No||277 (85.8)||283 (86.3)|
|≥1%||81 (25.1)||81 (24.7)|
|<1% or indeterminate||232 (71.8)||240 (73.2)|
|Not reported||10 (3.1)||7 (2.1)|
|Yes||34 (10.5)||41 (12.5)|
|No||279 (86.4)||278 (84.8)|
|Not reported||10 (3.1)||9 (2.7)|
|Stage at initial diagnosis7|
|Stage IV||167 (51.7)||173 (52.7)|
|Non-stage IV||150 (46.4)||148 (45.1)|
|Not reported||6 (1.9)||7 (2.1)|
|No. of metastatic sites2|||
|1||63 (19.5)||69 (21.0)|
|≥2||259 (80.2)||256 (78.0)|
|Most common sites of metastasis2|
|Lung||238 (73.7)||249 (75.9)|
|Lymph node||130 (40.2)||131 (39.9)|
|Liver||73 (22.6)||53 (16.2)|
|Bone||78 (24.1)||72 (22.0)|
|Adrenal gland||36 (11.1)||36 (11.0)|
Western and Northern European countries included: Czechia, Germany, Greece, Italy, Poland, Romania, Russian Federation, Spain, and the United Kingdom of Great Britain and Northern Ireland.7
Data are for tumor sites defined at baseline by the investigators according to RECIST v1.1. The number of target or nontarget lesions at baseline was not reported for 1 patient in the CABOMETYX + OPDIVO group and for 3 patients in the sunitinib group.2
Primary analysis results: OS2
Median follow-up time of 18.1 months; range: 10.6-30.6 months
- Pre-planned final analysis of OS (median follow-up: 32.9 months; range: 25.4-45.4 months): Median OS was 37.7 months for CABOMETYX + OPDIVO (95% Cl: 35.5-NR; n=323) compared with 34.3 months for sunitinib (95% Cl: 29.0-NR; n=328); HR=0.70 (95% Cl: 0.55-0.90)1,5,6
44-month follow-up analysis: OS4,10
Median follow up time of 44.0 months; range: 36.5-56.5 months4
Primary analysis results in the ITT population: PFS1
Median follow-up time of 18.1 months; range: 10.6-30.6 months2
Primary analysis results in the ITT population: ORR1
Median follow-up time of 18.1 months; range: 10.6-30.6 months2
orr was doubled1
44-month follow-up analysis results: PFS and ORR4
Median follow-up time of 44.0 months; range: 36.5-56.5 months
NCCN Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
NCCN Category 2A: Based on lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
The approval of CABOMETYX with OPDIVO in 1L aRCC was based on a randomized (1:1), open-label, Phase 3 trial vs sunitinib in patients with previously untreated aRCC with a clear-cell component.
1L=first-line; aRCC=advanced renal cell carcinoma; BICR=blinded independent central review; CI=confidence interval; CR=complete response; HR=hazard ratio; HRQoL=health-related quality of life; IMDC=International Metastatic RCC Database Consortium; IO=immunotherapy; ITT=intent to treat; IV=intravenous; NE=not estimable; ORR=objective response rate; OS=overall survival; PD-L1=programmed cell death ligand 1; PFS=progression-free survival; PFS-2=progression-free survival after subsequent therapy; PO=by mouth; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumors; TKI=tyrosine kinase inhibitor.
- CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc.
- Choueiri TK, Powles T, Burotto M, et al; CheckMate 9ER Investigators. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384(9):829-841.
- Motzer RJ, Choueiri TK, Powles T, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal cell carcinoma: outcomes by sarcomatoid histology and updated trial results with extended follow-up of CheckMate 9ER. Poster presented at Genitourinary Cancers Symposium; February 11-13, 2021.
- Burotto M, Powles T, Escudier B, et al. Nivolumab plus cabozantinib versus sunitinib for first-line treatment of advanced renal cell carcinoma: 3-year follow-up from the phase 3 CheckMate 9ER trial. Poster presented at Cancer Immunotherapy and Immunomonitoring Conference; April 24-27, 2023.
- Motzer RJ, Powles T, Burotto M, et al. Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomized, phase 3 trial. Lancet Oncol. 2022;23(7):888-898.
- Powles T, Choueiri TK, Burotto M, et al. Final overall survival analysis and organ-specific target lesion assessments with 2-year follow-up in CheckMate 9ER: nivolumab plus cabozantinib versus sunitinib for patients with advanced renal cell carcinoma. Poster presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium; February 17-19, 2022.
- Data on file. Topline 9ER. Exelixis, Inc.
- Savard M-F, Wells JC, Graham J, et al. Real-world assessment of clinical outcomes among first-line sunitinib patients with clear cell metastatic renal cell carcinoma (mRCC) by the International mRCC Database Consortium risk group. Oncologist. 2020;25(5):422-430.
- Heng DYC, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor–targeted agents: results from a large, multicenter study. J Clin Oncol. 2009;27(34):5794-5799.
- Data on file. Exelixis, Inc. 2022.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Kidney Cancer V1.2024. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed June 21, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org.