Nivolumab plus Ipilimumab Therapy

A new indication has been added to the product information of ipilimumab and nivolumab. Combination therapy with these medicines is now a first-line treatment option for unresectable or metastatic hepatocellular carcinoma in adults.

This approval was based on objective response rate and duration of response from a single-arm study. The recently published CheckMate 9DW study provides further evidence to support this indication. This open-label randomised, phase 3 trial compared the efficacy and safety of nivolumab plus ipilimumab with investigator’s choice of oral kinase inhibitor (lenvatinib or sorafenib).

With a median follow-up period of 35.2 months, overall survival (OS) was found to be significantly higher for the combination therapy:

• Nivolumab plus ipilimumab: median OS of 23.7 months (95% CI: 18.8–29.4)
• Oral kinase inhibitor: median OS of 20.6 months (95% CI: 17.5–22.5).

Immune-mediated adverse events were reported in 58% of patients in the nivolumab plus ipilimumab group. These events included hepatitis, thyroid disorders, rash, and diarrhoea/colitis. The incidence of severe to life-threatening adverse events was similar between the two groups (41% for nivolumab plus ipilimumab and 42% in the group receiving oral therapy).

The usual dosing regimen is nivolumab 1 mg/kg plus ipilimumab 3 mg/kg via intravenous infusion every three weeks for up to four doses. This is followed by nivolumab monotherapy until disease progression, unacceptable toxicity, or for up to two years.