On 22 January 2021, the US Food and Drug Administration (FDA) approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb Co.) and cabozantinib (Cabometyx, Exelixis) as first-line treatment for patients with advanced renal cell carcinoma (RCC).<\/p>\n
Efficacy was evaluated in CHECKMATE-9ER (NCT03141177), a randomised, open-label study in patients with previously untreated advanced RCC. Patients were randomised to receive either nivolumab 240 mg over 30 minutes every 2 weeks in combination with cabozantinib 40 mg orally once daily (n=323) or sunitinib 50 mg orally daily for the first 4 weeks of a 6-week cycle (4 weeks on treatment followed by 2 weeks off) (n=328).<\/p>\n
The study demonstrated a statistically significant improvement in progression-free survival (PFS), overall survival (OS) and confirmed overall response rate (ORR) for patients treated with nivolumab plus cabozantinib compared with those who received sunitinib.<\/p>\n
Median PFS per blinded independent central review (BICR) was 16.6 months versus 8.3 months; hazard ratio (HR) 0.51 (95% confidence interval [CI] 0.41, 0.64).<\/p>\n
Median OS was not reached in either arm; HR 0.60 (95% CI 0.40, 0.89).<\/p>\n
Confirmed ORR per BICR was 55.7% and 27.1% in the nivolumab plus cabozantinib and sunitinib arms, respectively.<\/p>\n
The most common adverse reactions (\u2265 20%) in patients receiving the combination of nivolumab and cabozantinib were diarrhoea, fatigue, hepatotoxicity, palmar-plantar erythrodysaesthesia syndrome, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.<\/p>\n
The recommended dose is nivolumab 240 mg every 2 weeks (30-minute intravenous infusion) or 480 mg every 4 weeks (30-minute intravenous infusion) in combination with cabozantinib 40 mg orally once daily without food until disease progression or unacceptable toxicity.<\/p>\n
Full prescribing information for Opdivo is available here<\/a> and full prescribing information for Cabometyx is available here<\/a>.<\/p>\n The nivolumab review used the Real-Time Oncology Review<\/a> pilot programme, which streamlined data submission prior to the filing of the entire clinical application. Both the nivolumab and the cabozantinib applications used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA\u2019s assessment. The FDA approved this application approximately one month ahead of the FDA goal date.<\/p>\n The nivolumab application was granted fast track review, and both the nivolumab and cabozantinib applications were granted priority review.<\/p>\n Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA\u2019s MedWatch Reporting System.<\/p>\n For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA\u2019s Oncology Center of Excellence<\/a> Project Facilitate<\/a>.<\/p>\n