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Nivolumab Ipilimumab Combination Outperforms Tyrosine Kinase Inhibitors in Unresectable Hepatocellular Carcinoma

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First-line treatment with nivolumab ipilimumab combination demonstrates a significant overall survival (OS) benefit versus treatment with lenvatinib or sorafenib in patients with unresectable hepatocellular carcinoma (HCC), according to first results of phase 3 CheckMate 9DW trial.


Tyrosine kinase inhibitors (TKI), such as lenvatinib and sorafenib, are first-line standard of Patients with unresectable hepatocellular carcinoma reported better results with nivolumab ipilimumab.care for patients with unresectable HCC, with a median overall survival of 12-14 months1. In CheckMate 040, nivolumab ipilimumab combination demonstrated clinically meaningful efficacy and manageable safety in patients with advanced HCC previously treated with sorafenib2.

CheckMate 9DW (NCT04039607) is a phase 3, randomized trial evaluating the efficacy and safety of nivolumab ipilimumab combination versus lenvatinib or sorafenib as a first-line therapy for patients with systemic therapy naïve, unresectable HCC. Dr. Peter Galle, MD, PhD, of Universitätsmedizin Mainz, in Germany, presented the first results3.

A total of 668 patients were 1:1 randomly assigned to receive nivolumab/ipilimumab (4 cycles) followed by nivolumab until disease progression or toxicity, or the investigator’s choice of lenvatinib (n=275) or sorafenib (n=50) until progression or toxicity. The primary outcome measurement was overall survival (OS) and the secondary endpoints were response rate and time to deterioration.

After a median follow-up of 3 years, median OS was 23.7 months (95% CI 18.8 –29.4) in the nivolumab/ipilimumab arm versus 20.6 months (95% CI 17.5-22.5) in the lenvatinib/sorafenib arm (HR 0.79; 95% CI 0.65 –0.96; P=0.018). 36-Month OS rate was 38% and 24%, respectively. OS benefit of nivolumab/ipilimumab was observed in all prespecified subgroups.

Objective response rate was higher in the nivolumab/ipilimumab arm: 36% (7% complete responders, 29% partial responders) versus 13% (2% complete responders, 11% partial responders). The median duration of response was 30.4 months with nivolumab/ipilimumab (n=121) versus 12.9 months with lenvatinib/sorafenib (n=44).

Comparable rates of treatment-related AEs was observed in both arms and were as expected. Nivolumab/ipilimumab therapy resulted in a statistically significant reduced risk (24%) of symptom deterioration versus lenvatinib/sorafenib. In addition, participants treated with nivolumab/ipilimumab had an improvement in health-related quality of life after week 29, while participants treated with lenvatinib/sorafenib had a clinically meaningful decline at several time points.

“These results support nivolumab ipilimumab combination as a potential new first-line standard of care treatment for patients with unresectable hepatocellular carcinoma,” concluded Dr. Galle.

Medical writing support was provided by Marten Dooper, PhD.

Copyright ©2024 Medicom Medical Publishers

The post Nivolumab Ipilimumab Combination Outperforms Tyrosine Kinase Inhibitors in Unresectable Hepatocellular Carcinoma first appeared on Physician's Weekly.


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