FDA approves nivolumab plus ipilimumab for unresectable or metastatic hepatocellular carcinoma

On April 11, 2025, the Food and Drug Administration (FDA) officially approved nivolumab (Nivolumab; trade name Opdivo, produced by Bristol-Myers Squibb) and ipilimumab (< /span>Ipilimumab; brand name Yervoy, also manufactured by Bristol-Myers Squibb Company), as a first-line treatment option for adult patients with unresectable or metastatic hepatocellular carcinoma (HCC). This approval provides a new treatment option for patients with advanced liver cancer and opens up a new direction for the prospects of liver cancer immunotherapy.

Hepatocellular carcinoma is the most common type of primary liver cancer in the world, especially in Asia and Africa, with high morbidity and mortality. For patients with unresectable or metastatic hepatocellular carcinoma, the existing treatment methods are mostly systemic treatments, such as molecular targeted drugs and immunotherapy, but the treatment effect and extension of survival are still limited. Therefore, the FDA's approval of the combination therapy of nivolumab and ipilimumab is of great clinical significance. It provides new hope for patients facing advanced liver cancer.

1. Efficacy and safety

This timeThe basis for FDA approval mainly comes from the CHECKMATE-9DW trial (NCT04039607), which is a randomized, open-label clinical trial conducted in 668 adult patients with unresectable or metastatic hepatocellular carcinoma (HCC). The patients in the trial were all patients with histologically confirmed HCC, liver cancer with Child Pugh grade A and ECOG performance status of 0 or 1, and had not received systemic treatment for advanced disease before inclusion in the trial. Patients were randomized in the trial to compare two treatment options: one group received a combination of nivolumab (1 mg/kg) and ipilimumab (3 mg/kg), intravenously infused every 3 weeks for up to four doses, followed by nivolumab (480 mg) alone every 4 weeks as an intravenous injection; the other group of patients received lenvatinib or sorafenib, as the standard treatment option chosen by the investigators.

The main efficacy evaluation index of this trial is overall survival (OS), which is the time from the beginning of treatment to the patient's death from any cause. In addition, patients' tumor response was evaluated using RECIST 1.1 criteria, and the overall response rate (ORR) of each group was calculated as an auxiliary efficacy indicator.

The trial results show that the median of the nivolumab plus ipilimumab groupThe OS was 23.7 months (95% CI, 18.8-29.4), which was significantly better than the median OS of 20.6 months (95% CI, 17.5-22.5) in the lenvatinib or sorafenib group. Specifically, compared with the standard treatment group, the hazard ratio (HR) of the nivolumab + ipilimumab group was 0.79 (95% CI, 0.65-0.96), and the p value was <0.0180, showing a clear survival advantage. In addition, the ORR of the nivolumab + ipilimumab group was 36.1% (95% CI, 31.0-41.5), which was much higher than the 13.2% (95% CI, 9.8-17.3) of the lenvatinib or sorafenib group, and the p value was <0.0001, proving the superiority of nivolumab and ipilimumab combination therapy in promoting tumor response.

2. Adverse reactions and safety

In clinical application, common adverse reactions of nivolumab and ipilimumab include rash, itching, fatigue and diarrhea. These adverse reactions have a higher incidence during treatment, especially rash and itching. Nonetheless, these adverse reactions are controllable in the vast majority of patients, and most are mild to moderate and can be alleviated with symptomatic treatment. In clinical practice, doctors usually adjust the dosage or dosage regimen of drugs according to the specific conditions of the patient to minimize the impact of adverse reactions on the patient. In general, the safety profile of combined treatment with nivolumab and ipilimumab is relatively good, and most of the side effects are acceptable.

According to the recommended medication regimen approved by the FDA, the standard dose of nivolumab is 1 mg/kg, combined with ipilimumab (3 mg/kg), and administered intravenously every three weeks for up to four times. After completing four combination treatments, patients will need to switch to nivolumab alone, at a dose of 240 mg every two weeks or 480 mg every four weeks, both intravenously. This treatment regimen is continued until disease progression or unacceptable toxicity occurs.

References:https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-ipilimumab-unresectable-or-metastatic-hepatocellular-carcinoma