Regulatory Decision Summary for Opdivo

Authorization was based on an international, randomized, open label, phase III trial (CA2099ER). Treatment-naïve patients (n = 651) with advanced (not amenable to curative surgery or radiation therapy) or metastatic renal cell carcinoma (RCC) received either Opdivo (240 mg intravenously every 2 weeks) combined with cabozantinib (40 mg once daily, orally), or sunitinib 50 mg once daily for 4 weeks followed by 2 weeks off, every cycle. The study met its primary efficacy endpoint of progression-free survival (PFS). The median PFS was 16.6 months with Opdivo plus cabozantinib and 8.3 months with sunitinib. Findings from the secondary efficacy endpoint of overall survival was supportive.

The most common adverse reactions (ARs) reported in at least 10% of patients who received Opdivo plus cabozantinib were diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome, rash, pruritus, hypertension, hypothyroidism, liver enzyme elevation, arthralgia, anemia, thrombocytopenia, proteinuria, etc. There are more risks associated with the combination therapy than what was observed with nivolumab or cabozantinib alone. Risk mitigation is achieved through close monitoring, especially of liver function tests, and the appropriate use of systemic corticosteroid treatment when necessary. View the Opdivo Product Monograph for details.

The recommended dose of Opdivo is either 240 mg every 2 weeks or 480 mg every 4 weeks intravenously (up to 2 years) in combination with cabozantinib 40 mg orally once every day.

Overall, the benefit/risk profile of Opdivo in combination with cabozantinib is considered favourable for the first-line treatment of adult patients with advanced (not amenable to curative surgery or radiation therapy) or metastatic RCC