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ASCO 2024 – Yervoy makes the difference in front-line liver cancer

Checkmate-9DW’s control arm outperformed historical survival numbers, but despite this Opdivo plus Yervoy still managed to beat it. That’s the key message from today’s late-breaking ASCO presentation of data from this study, which should see Bristol Myers Squibb’s doublet join AstraZeneca’s Imfinzi plus Imjudo, and Roche’s Tecentriq plus Avastin as approved front-line liver cancer therapies. Checkmate-9DW already surprised when it was toplined positively in March; not only had Bristol’s Checkmate-459 study of Opdivo monotherapy in first-line liver cancer failed to beat Nexavar on OS, Checkmate-9DW had suffered extensive delays and had its enrolment target cut from 1,084 to 732 patients. The delays might be explained by the fact patients lived longer than expected – those on the control arm of physician’s choice Nexavar or Lenvima recording median OS of 20.6 months, against the 14-15 months Lenvima control had scored in Astra’s Himalaya and Roche’s Imbrave-150 trials. The result for Opdivo plus Yervoy, an improvement of 3.1 months, might seem paltry, but the control arm’s strong performance, plus statistical significance and a strong win on ORR (36% versus 13%) suggests that it’s robust. The penalty is Yervoy’s notorious toxicity: 13% of active cohort patients in Checkmate-9DW withdrew owing to grade 3/4 treatment-related adverse events, versus 6% for control.


Cross-trial comparison in 1st-line liver cancer





RegimenTecentriq + AvastinImfinzi + ImjudoOpdivo + Yervoy
mOS19.2mth vs 13.4mth for Nexavar16.4mth vs 13.8mth for Nexavar23.7mth vs 20.6mth for Lenvima or Nexavar
HR=0.66, p<0.001HR=0.78, p=0.0035HR=0.79, p<0.0001
NoteUS approved Jun 2020US approved Oct 2022Bristol to discuss results with health authorities

Source: OncologyPipeline.