ASCO: Bristol Myers challenges Roche and AstraZeneca with Opdivo-Yervoy in first-line liver cancer

Bristol Myers Squibb (BMS) has made a significant breakthrough with its immunotherapy duo, Opdivo and Yervoy, by extending the survival rate of newly diagnosed liver cancer patients. In a phase 3 trial named CheckMate-9DW, the combination therapy demonstrated a survival rate of 38% at three years, setting a new benchmark in the field. This trial outcome was shared at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

The study revealed that Opdivo and Yervoy reduced the risk of death by 21% when compared to either Merck and Eisai’s Lenvima or Bayer’s Nexavar in patients with previously untreated advanced hepatocellular carcinoma. Patients treated with the BMS regimen lived a median of 23.7 months, which was 3.1 months longer than those treated with the tyrosine kinase inhibitors (TKIs), Lenvima or Nexavar.

However, there is some ambiguity regarding the effectiveness of Opdivo and Yervoy compared to Nexavar specifically, as recent analyses have suggested that Lenvima might be a stronger contender in first-line liver cancer treatment. BMS' Chief Medical Officer, Dr. Samit Hirawat, clarified that the trial was not intended to compare the Opdivo-Yervoy regimen against each TKI separately.

Interestingly, the control group in the trial, which received either Lenvima or Nexavar, demonstrated a median overall survival (OS) of 20.6 months. This is noteworthy because, in 2022, Lenvima achieved a median OS of 19 months for first-line liver cancer patients in Merck’s LEAP-002 trial, which was the longest recorded for the drug at that time. In that study, the combination of Keytruda and Lenvima did not significantly outperform Lenvima alone, showing a median OS of 21.2 months.

The BMS PD-1/CTLA4 combination of Opdivo and Yervoy is now poised to compete with Roche’s PD-L1/VEGF combination of Tecentriq and Avastin, as well as AstraZeneca’s PD-L1/CTLA4 regimen of Imfinzi and Imjudo. Both Tecentriq-Avastin and Imfinzi-Imjudo received FDA approvals for first-line liver cancer treatments based on data comparing them to Nexavar.

In the IMbrave150 trial, the Tecentriq and Avastin combo initially showed a 42% reduction in the risk of death, although the median OS was not reached at the time. Later analysis reported a median OS of 19.2 months for the Roche regimen versus 13.4 months for Nexavar. Similarly, in the HIMALAYA study, AstraZeneca's Imfinzi and Imjudo demonstrated a median OS of 16.4 months compared to Nexavar’s 13.8 months, with a 22% reduction in death risk.

Besides these major pharmaceutical players, Elevar Therapeutics and Jiangsu Hengrui Pharma are also attempting to enter the first-line liver cancer market. Their combination of camrelizumab and rivoceranib showed promise but faced FDA rejection due to manufacturing and clinical trial inspection issues.

In their CARES-310 study, Elevar and Hengrui’s combination demonstrated a median OS of 22.1 months versus 15.2 months for Nexavar at interim analysis, with a 38% reduction in death risk. The final OS analysis showed a median OS of 23.8 months, although the reduction in death risk decreased to 36%.

Given the variations in trial populations, follow-up times, and comparator arms, direct comparisons between these therapies are challenging. However, Opdivo and Yervoy have set a new standard with their three-year survival rate, surpassing the previous record held by the Imfinzi-Imjudo duo. Dr. Hirawat emphasized that treatment choices will depend on patient characteristics and each therapy's profile, underscoring the potential of Opdivo and Yervoy to benefit patients for extended periods.