ESMO GI 2025 | CheckMate 9DW: HRQoL and efficacy in patients who discontinued due to adverse events

The CheckMate 9DW is a Phase III trial that tested the combination of nivolumab plus ipilimumab versus lenvatinib or sorafenib, mostly lenvatinib, in patients with advanced stage HCC. The trial is positive, already published, and the combination of nivolumab plus ipilimumab has been approved by the FDA, by the EMA, is included in the ESMO guidelines, so it’s a standard of care. The authors presented the quality of life data and also new data in terms of safety and efficacy. It’s important that 90% of the patients filled out the questionnaires for the quality of life analysis, both at baseline and during treatment. Another important point is that the authors used questionnaires that are specific for HCC, not general quality of life questionnaires. The results show that there is a clear benefit in quality of life for nivo-ipi compared to lenvatinib or sorafenib in terms of time to deterioration of quality of life that is much longer with the combination of immunotherapy compared to the tyrosine kinase inhibitors. Another aspect that they evaluated is how much patients are bothered by adverse events related to the treatment and in the nivo-ipi arm, the patients are less bothered by the adverse events compared to the tyrosine kinase inhibitor arm, so this is benefiting in quality of life. And the other important aspect that they presented new data in terms of safety, the immune-mediated adverse events occurred mostly within three months of treatment initiation. And if we look at the liver and skin toxicity within the first month, This is an important piece of information for clinical practice because clinicians can know when they see the adverse event, when they should expect the adverse event, so they should carefully manage patients within the first months of treatment initiation. And another important point is that the discontinuation of treatment due to treatment-related adverse events and the use of steroids to manage immune-mediated adverse events have no impact on overall survival. So there is no negative impact on overall survival. One point that is still not clear or not well explained in this trial is that the first part of the survival curve show a crossing. so in the first six months of treatment there is a benefit in survival from the tyrosine kinase inhibitor compared to nivo-ipi and then there is a crossing and it’s not very clear what happened in the first part of the treatment in the first months of treatment and this is something that should still be investigated and should be clarified but anyway the trial is positive but this is a new standard of care and the quality of life analysis support the use of nivo-ipi in clinical practice.