(UroToday.com) The 2024 GU ASCO annual meeting featured a renal cell carcinoma session and a presentation by Dr. Maria Bourlon discussing 55-month follow-up of the CheckMate 9ER trial assessing nivolumab + cabozantinib versus sunitinib for previously untreated advanced renal cell carcinoma.
Nivolumab + cabozantinib demonstrated superior progression-free survival, overall survival, and objective response rate vs sunitinib in patients with previously untreated advanced RCC in the primary analysis of the phase 3 CheckMate 9ER trial (18.1 months median follow-up).1 Additionally, nivolumab + cabozantinib maintained efficacy benefits vs sunitinib with 44.0 months median follow-up. At the GU ASCO 2024 annual meeting, Dr. Bourlon reported updated efficacy in intent-to-treat (ITT) patients and by International Metastatic RCC Database Consortium (IMDC) risk, and safety with extended follow-up.
Patients with advanced RCC were randomized to nivolumab 240 mg every 2 weeks + cabozantinib 40 mg QD vs sunitinib 50 mg QD (4 weeks of 6-week cycles) until disease progression or unacceptable toxicity, with up to 2 years of nivolumab:
The primary endpoint was progression-free survival per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included overall survival, objective response rate per RECIST v1.1 by BICR, and safety.
Overall, 323 patients were randomized to nivolumab + cabozantinib and 328 to sunitinib (ITT). With a 55.6 month median (48.1 month minimum) follow-up for overall survival (ITT), median progression-free survival was 16.4 vs 8.4 months (HR 0.58, 95% CI 0.49-0.70) and median overall survival was 46.5 vs 36.0 months (HR 0.77, 95% CI 0.63-0.95) with nivolumab + cabozantinib vs sunitinib. Objective response rate was 55.7% (95% CI 50.1-61.2) vs 27.7% (95% CI 23.0-32.9), including 13.6% vs 4.6% of patients achieving a complete response and 6.5% vs 13.7% having progressive disease, respectively:
In the IMDC favorable-risk population, the median progression-free survival was 21.4 vs 12.8 months (HR 0.69, 95% CI 0.48-1.00) and median overall survival was 52.9 vs 58.9 months (HR 1.10, 95% CI 0.69-1.75) with nivolumab + cabozantinib vs sunitinib. Objective response rate was 66.2% vs 44.4%, including 16.2% vs 8.3% of patients achieving a complete response and 2.7% vs 2.8% having progressive disease, respectively:
In the IMDC intermediate/poor risk population, the median progression-free survival was 15.4 vs 7.1 months (HR 0.56, 95% CI 0.45-0.68) and median overall survival was 43.9 vs 29.3 months (HR 0.73, 95% CI 0.58-0.91) with nivolumab + cabozantinib vs sunitinib. Objective response rate was 52.6% vs 23.0%, including 12.9% vs 3.5% of patients achieving a complete response and 7.6% vs 16.8% having progressive disease, respectively:
In the ITT population, the median time to response was 2.8 (range 1.0-22.2) vs 4.3 (range 1.7-30.4) months for nivolumab + cabozantinib vs sunitinib, and median duration of response was 22.0 (95% CI 18.0-25.2) vs 15.2 (95% CI 10.9-19.3) months. When looking at efficacy by baseline organ sites of metastases, the following summarizes the findings stratified by liver, bone, and lung metastases, all favoring nivolumab + sunitinib:
Among all treated patients (320 patients each arm), any-grade (grade ≥ 3) treatment-related adverse events occurred in 97.5% (67.5%) vs 93.1% (55.3%) with nivolumab + cabozantinib vs sunitinib. Any-grade treatment-related adverse events led to discontinuation of nivolumab or cabozantinib in 28.1% of patients (nivolumab only, 10.0%; cabozantinib only, 10.3%; nivolumab + cabozantinib simultaneously, 6.6%; nivolumab + cabozantinib sequentially, 1.3%) and of sunitinib in 10.9% of patients:
For health related quality of life, change from baseline in EQ-5D-3L Utility Index UK favored nivolumab + cabozantinib versus sunitinib in ITT patients. Additionally, change from baseline in these measures favored nivolumab + cabozantinib in IMDC intermediate/poor risk patients, with no differences observed between arms in IMDC favorable risk patients. Overall, 49% of patients in the nivolumab + cabozantinib arm versus 55% of patients in the sunitinib arm had subsequent therapies. Among 320 treated patients in each arm, 11% versus 6% of patients remained on therapy, respectively, at the time of the data cutoff date:
Dr. Bourlon concluded her presentation discussing 55-month follow-up of the CheckMate 9ER trial with the following take-home points:
- With 55.6 months of median follow-up, nivolumab + cabozantinib continues to maintain meaningful long-term efficacy benefits over sunitinib
- Progression free survival and objective response rate favored nivolumab + cabozantinib regardless of IMDC risk and efficacy favored nivolumab + cabozantinib in specific subgroups by baseline organ sites of metastases
- No new safety concerns were identified
- Health related quality of life was consistent with previous follow-ups and favored nivolumab + cabozantinib in the ITT population and in intermediate/poor risk patients
- These results continue to support nivolumab + cabozantinib as a standard of care for previously untreated advanced RCC
Presented by: Maria T. Bourlon, MD, MSc, Urologic Oncology Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Jan 25 – Sat, Jan 27, 2024.
Related content: Cabozantinib and Nivolumab Combination Therapy Shows Durable Efficacy in Advanced Kidney Cancer - María Bourlon
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