Bristol-Myers Squibb (BMS) has secured FDA approval for its immunotherapy combination of Opdivo (nivolumab) and Yervoy (ipilimumab) as a first-line treatment for patients with unresectable or metastatic hepatocellular carcinoma (HCC), the most common form of liver cancer.
The approval is based on positive results from the open-label Phase III CheckMate-9DW trial, which demonstrated a significant survival advantage for the dual immunotherapy approach compared to current standard treatments.
Survival Benefit Drives Regulatory Decision
In the pivotal CheckMate-9DW trial, patients treated with the Opdivo/Yervoy combination showed a 21% reduced risk of death compared to those receiving tyrosine kinase inhibitor (TKI) monotherapy with either Bayer's Nexavar (sorafenib) or Eisai's Lenvima (lenvatinib). The median overall survival reached 23.7 months with the immunotherapy combination versus 20.6 months in the control arm.
"The CheckMate-9DW approval is an important advancement for patients, considering the incidence of liver cancer has tripled in the last four decades, yet, prognosis for HCC patients remains poor," said study investigator Dr. Aiwu Ruth He of MedStar Georgetown University Hospital. "The availability of a new first-line treatment option that demonstrated a deep response can offer adults with this form of liver cancer long-term overall survival and may help address an unmet need."
Competitive Landscape in HCC Treatment
This approval reintroduces an Opdivo-based regimen to the HCC treatment landscape after BMS withdrew the drug as a second-line treatment in 2021 following a failed confirmatory trial. The new first-line indication positions the combination to compete with other immunotherapy-based approaches that have gained approval in recent years.
Current alternatives include Roche's Tecentriq (atezolizumab) plus bevacizumab, approved in 2020, and AstraZeneca's Imfinzi (durvalumab) with Imjudo (tremelimumab), which received FDA clearance in 2022. While these regimens have also shown improvements in survival, investigators from the CheckMate-9DW trial suggest the robust OS data with Opdivo/Yervoy may establish it as a preferred first-line option for advanced HCC.
"Given the strength of evidence from the trial, especially considering the selection and performance of a strong comparator arm, I believe that Opdivo plus Yervoy has the potential to become a standard of care for the first-line treatment of patients with unresectable or metastatic HCC," Dr. He added.
Treatment Considerations and Clinical Implications
The dual immunotherapy approach represents a continuing shift away from single-agent TKIs toward combination immunotherapy as the preferred first-line treatment for advanced HCC. However, clinicians will need to consider the known toxicity profile of the Opdivo/Yervoy combination, particularly related to Yervoy, which can be challenging for some patients to tolerate.
Wendy Short Bartie, BMS oncology commercialization senior vice president, commented: "Bringing Opdivo plus Yervoy to patients with HCC in the first-line setting is a testament to our ongoing commitment to research and delivering important progress for people living with cancer. Today's approval builds on the legacy of our dual immunotherapy and the value it has brought to patients for years."
Historical Context and Regulatory Path
The Opdivo/Yervoy combination initially received accelerated approval from the FDA in 2020 based on the Phase I/II CheckMate-040 trial as a second-line treatment for HCC patients previously treated with sorafenib. The current approval grants full regulatory clearance and extends the regimen's use to the first-line setting.
This approval represents BMS's second FDA approval in a matter of days for the Opdivo/Yervoy combination, further strengthening the company's position in the gastrointestinal cancer space and providing a valuable new option for patients facing a challenging diagnosis with historically limited treatment options.
