Nivolumab/ipilimumab combination outperforms TKIs in unresectable HCC

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

Before immunotherapy, tyrosine kinase inhibitors (TKIs), such as lenvatinib and sorafenib, were the only first-line standard-of-care for patients with unresectable HCC, resulting in a median OS of 12–14 months [1]. In CheckMate 040, the combination of nivolumab/ipilimumab demonstrated clinically meaningful efficacy and manageable safety in patients with advanced HCC previously treated with sorafenib [2].

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

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

After a median follow-up of 3 years, the median OS was 23.7 months in the nivolumab/ipilimumab arm versus 20.6 months in the lenvatinib/sorafenib arm (HR 0.79; 95% CI 0.65–0.96; P=0.018). The 36-month OS rates were 38% and 24%, respectively. An 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 adverse events were observed in both arms and were in line with previous findings. Nivolumab/ipilimumab therapy significantly reduced the risk (24%) of symptom deterioration compared with lenvatinib/sorafenib. In addition, participants treated with nivolumab/ipilimumab had an improved health-related quality-of-life after week 29, whereas those treated with lenvatinib/sorafenib had a clinically meaningful decline at several timepoints.

“These results support the nivolumab/ipilimumab combination as a potential new first-line standard-of-care treatment for patients with unresectable hepatocellular carcinoma,” concluded Dr Galle. This data is in line with recently updated results of the phase 3 HIMALAYA trial, showing a median OS of 16.4 months with STRIDE regimen versus 13.8 months with sorafenib (HR 0.78) [4].

1. Kudo M, et al. Lancet 2018;391:1163-1173.
2. Yau T, et al. JAMA Oncol. 2020;6:e204564.
3. Galle PR, et al. Nivolumab plus ipilimumab vs lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma: first results from CheckMate 9DW. Abstract LBA4008, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.
4. Sangro B, et al. Ann Oncol. 2024 May;35(5):448-457.

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Posted on 18 July 202418 July 2024