Opdivo, celebrating its 10th anniversary of approval in South Korea, is expected to expand its influence by broadening the indication of its combination therapy with Yervoy to include first-line treatment for hepatocellular carcinoma (HCC).

Experts assess that this will become a primary treatment option, given the unmet need in the existing first-line HCC treatment landscape, where tyrosine kinase inhibitors (TKIs) have been the standard of care for over 10 years. Although reimbursement remains a challenge, there is a view that it will become a new standard of care.

Ono Pharma Korea and BMS Korea held a press conference on the 22nd of this month, highlighting the expanded indication of Opdivo (nivolumab) and Yervoy (ipilimumab) combination therapy for first-line HCC treatment.

Opdivo is a PD-1 (programmed cell death-1) immune checkpoint inhibitor that reactivates the body's immune system to mount an anti-tumor immune response by inhibiting the PD-1 and PD-1 ligand pathways.

First introduced in Korea in 2015 as a second-line treatment for malignant melanoma, as of July 2025, it has secured 24 indications across a total of 11 cancer types.

On July 10, the combination therapy of Opdivo and Yervoy received additional approval from the Ministry of Food and Drug Safety (MFDS) for the first-line treatment of unresectable or metastatic HCC.

The CheckMate-9DW study, which served as the basis for the first-line approval of the Opdivo-Yervoy combination therapy for HCC, is receiving a positive evaluation for setting lenvatinib as a comparator drug.

Dr. Do Young Kim of the Department of Gastroenterology at Severance Hospital explained, "Most treatments approved for first-line HCC treatment have used sorafenib as a comparator, but this study also set lenvatinib, which is a relatively newer treatment option, as a comparator." He added, "The significance lies in confirming the superiority of the Opdivo+Yervoy combination therapy under conditions more similar to the current clinical environment, as lenvatinib was administered to 85% of the overall comparator arm."

The Opdivo+Yervoy combination therapy, based on the CheckMate-9DW study, demonstrated a median overall survival (OS) of 23.7 months, with a median follow-up period of 35.2 months.

The comparator group had an OS of 20.5 months, showing that the Opdivo+Yervoy combination arm had a 21% lower risk of death than the comparator arm. The OS rates for the Opdivo+Yervoy combination therapy group at 2 and 3 years were 49% and 38%, respectively, surpassing the comparator group's 39% and 24%.

Dr. Kim said, "The CheckMate-9DW study results showed that the improved overall survival benefit of the Opdivo+Yervoy combination therapy was maintained up to the 3-year mark compared to sorafenib and lenvatinib," and added, "This confirms its sustained efficacy as a dual immunotherapy."

Dr. Kim also mentioned, "The Opdivo+Yervoy combination therapy showed approximately a threefold improvement in both response rate and complete response rate compared to the comparator group, and the median duration of response was 30.4 months. In other words, patients who respond to Opdiv+Yervoy combination therapy, long-term therapeutic effects of over 2.5 years can be expected."

"Opdivo+Yervoy expected to address unmet needs in HCC"

Dr. Chang-hoon Yoo, Professor of the Department of Medical Oncology at Asan Medical Center in Seoul, highlighted the possibility that the Opdivo+Yervoy combination therapy could become a new standard of care in HCC, where existing treatments have faced limitations.

According to Dr. Yoo, liver cancer (disease code C22) had the second-highest mortality rate among major cancer types in Korea as of 2023, at 11.9%, following lung cancer (21.9%). In the same year, total deaths due to liver cancer amounted to 10,136.

Dr. Yoo explained, "The 5-year survival rate for advanced HCC is reported to be less than 5%, and TKIs, which have been used as standard first-line treatment for over 10 years in the existing treatment environment, only showed a survival period of around one year." He added, "While immunotherapy-based combination therapies were introduced as new treatments for HCC in 2022, changing the treatment landscape, there was still a demand for additional alternatives in terms of survival duration, response rates, and side effects like variceal bleeding."

Currently, Dr. Yoo's opinion is that the approval of Opdivo+Yervoy combination therapy for the HCC indication makes it the first treatment to consider for prescription.

Dr. Yoo stated, "The CheckMate-9DW clinical trial results, which showed high response rates and the potential for long-term survival of approximately two years, demonstrated its potential to serve as a new standard of care in first-line HCC treatment in Korea." He added, "The treatment response of Opdivo+Yervoy combination therapy was consistent regardless of the patient's liver function, providing a basis for selecting it as a first-line option considering the patient's condition."

He also assessed, "It can be primarily considered for patients whose main treatment goal is long-term survival."

Notably, Dr. Yoo anticipated no concerns regarding safety, given that the Opdivo+Yervoy combination therapy has already accumulated sufficient clinical experience through the prior application system for several years.

Dr. Yoo said, "The safety profile was similar to the existing profiles of each drug, and adverse events were mostly manageable," and added, "Opdivo and Yervoy have accumulated sufficient clinical experience in combination therapy for HCC through the prior application system for several years now."

Dr. Yoo further added, "Immune-related adverse events can be safely managed through early detection and monitoring, and in actual clinical studies, cases where immune-related adverse events led to treatment discontinuation were rare. Concerns regarding adverse event management are expected to be minimal."