Home > Gastroenterology > HIMALAYA: Durvalumab ± tremelimumab new first-line option for unresectable HCC

HIMALAYA: Durvalumab ± tremelimumab new first-line option for unresectable HCC

Presented By
Prof. Ghassan Abou-Alfa, Memorial Sloan Kettering Center, NY, USA
ASCO GI 2022
Tremelimumab plus durvalumab improved the overall survival (OS) of patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib. Also, durvalumab monotherapy was non-inferior to sorafenib. Durvalumab monotherapy and the combination with tremelimumab had manageable safety profiles and may represent new first-line treatment options for this population [1].

“First-line options for patients with uHCC have been limited, with sorafenib and lenvatinib being the main options,” Prof. Ghassan Abou-Alfa (Memorial Sloan Kettering Center, NY, USA) said. “These agents have been associated with a median OS of approximately 1 year and quality-of-life reducing toxicity.” Recently, atezolizumab and bevacizumab outperformed sorafenib [2]. Also, tremelimumab, a CTLA-4 inhibitor, plus durvalumab, a PD-L1 inhibitor, showed promising activity in this population in a phase 2 trial [3].

The current open-label, multicentre, phase 3 HIMALAYA trial (NCT03298451) randomised patients with uHCC 1:1:1 to tremelimumab 300 mg single dose plus durvalumab 1,500 mg every 4 weeks (T300+D regimen; n=393), durvalumab monotherapy (n=389), or sorafenib 400 mg twice daily (n=389). The primary objective was to compare the T300+D regimen with sorafenib regarding OS.

T300+D was superior to sorafenib in terms of median OS (16.4 vs 13.8 months; HR 0.78; P=0.0035). The OS difference between the 2 treatment regimens increased over time: 18-month OS rates were 48.7% and 41.5%; 36-month OS rates were 30.7% and 20.2% (see Figure). The superiority of T300+D over sorafenib was consistent across subgroups. Furthermore, the median OS for patients on durvalumab monotherapy was non-inferior to that of patients in the sorafenib arm (16.6 vs 13.8 months; HR 0.86).

Figure: Overall survival of T300+D versus sorafenib [1]

The safety profiles of the novel treatment regimens were manageable. Grade 3 or 4 adverse events (AEs) occurred in 25.8%, 12.9%, and 36.9% of the patients on T300+D, durvalumab monotherapy, and sorafenib, respectively. Hepatic or haemorrhagic SMQ events were limited in the T300+D arm, with 7.0% and 0.5% grade 3 or higher events in this treatment arm. The prevalence of immune-mediated AEs met the expectations of the authors. The most common grade 3 or 4 AEs in the T300+D and durvalumab arms were hepatic events (4.1%, 4.4%), diarrhoea (3.6%, 0.3%), and dermatitis/rash (1.8%, 0.3%).

In conclusion, the authors suggested that durvalumab ± tremelimumab is a possible new standard for patients unable to receive bevacizumab.

  1. Abou-Alfa GK, et al. Phase 3 randomized, open-label, multicenter study of tremelimumab and durvalumab as first-line therapy in patients with unresectable hepatocellular carcinoma: HIMALAYA. Abstract 379, ASCO GI 2022, 20–22 January.

  2. Finn RS, et al. N Engl J Med 2020;382:1894–1905.

  3. Kelley RK, et al. J Clin Oncol. 2021;39(27):2991–3001.


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