Real-World Results of Durvalumab/Tremelimumab in U-HCC Show Promise Despite Line of Therapy

Patients experienced similar safety and efficacy if they received durvalumab plus tremelimumab in the first-line or later-line setting for unresectable hepatocellular carcinoma.

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In a real-world setting, durvalumab plus tremelimumab was safe and effective for patients with unresectable hepatocellular carcinoma (u-HCC) whether they were treated in the first-line setting or they received the therapy as a later-line treatment. The results were published in Drugs – Real-World Outcomes.¹

The FDA approved the combination therapy in 2022 based on the results of the HIMALAYA trial (NCT03298451).^2,3 The phase 3 trial found median overall survival (OS) was 16.4 months on the combination compared with 16.6 months on durvalumab monotherapy, and 13.77 months for sorafenib. The OS at 36 months was 30.7% for the combination vs 24.7% on the monotherapy and 20.2% for sorafenib. Recently published updated data from the trial on the 4-year OS found the 48-month OS was 25.2% for the combination compared with 15.1% for sorafenib.⁴

Historically, transcatheter ablation chemoembolization was the recommended treatment for patients with u-HCC, the authors explained.¹ Since the HIMALAYA trial excluded patients who had previously been treated with molecularly targeted agents (MTAs), such as sorafenib, or immune checkpoint inhibitors (ICIs), such as atezolizumab, the researchers also wanted to assess the treatment results and safety profile of durvalumab/tremelimumab in patients who had previously been treated with MTAs or ICIs.

In the real-world setting, 22 patients were evaluated: 10 in the first-line group and 12 in the later-line group. The patients had all been treated with durvalumab/tremelimumab at Iwate Medical University in Japan between 2023 and 2024. The median age was 75.9 years and 86.4% were male.

During the observation period, 17 patients discontinued the treatment because of progressive disease (n = 12) or adverse events (AEs; n = 4). The difference in median progression-free survival for both groups was not statistically significant (4.7 months in first line vs 2.9 months in later line; P = 0.85).

At 8 weeks, the objective response rate (ORR) was 9.1% and the disease control rate (DCR) was 59.1% based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Using the modified RECIT, the ORR was 9.1% and the DCR was 68.2%. The ORRs and DCRs did not differ between the groups.

A total of 14 patients (63.6%) experienced 25 AEs. The most common (≥ 10%) AEs were infusion reactions (27.3%), fatigue (22.7%), diarrhea or colitis (18.2%), decreased appetite (13.6%), and pruritus or rash (13.6%). The incidence of AEs did not differ significantly between the 2 groups.

The study also found that hepatic functional reserve was well preserved in the early stages of treatment with the combination. Modified albumin-bilirubin grade and Child-Pugh scores were stable throughout the 8 weeks of treatment.

The authors noted that the single-center nature of the study was one limitation, as well as the small number of patients and the short observation period. Due to these limitations, they could not assess OS.

“…we presume that Durva/Treme is a candidate as a universal therapeutic strategy and it is a potentially promising treatment option for patients with u-HCC,” they concluded. “Further larger trials with long-term observation are needed to validate the speculation.”

References

1. Fujiwara Y, Kuroda H, Abe T, et al. Early clinical outcomes of durvalumab plus tremelimumab in unresectable hepatocellular carcinoma: a real-world comparison with first-line or later-line treatment. Drugs Real World Outcomes. Published online October 10, 2024. doi:10.1007/s40801-024-00458-7

2. FDA approves tremelimumab in combination with durvalumab for unresectable hepatocellular carcinoma. News release. FDA. October 24, 2022. Accessed November 22, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-unresectable-hepatocellular-carcinoma

3. Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022;1(8):EVIDoa2100070. doi:10.1056/EVIDoa2100070

4. Sangro B, Chan SL, Kelley RK, et al; HIMALAYA investigators. Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Ann Oncol. 2024;35(5):448-457. doi:10.1016/j.annonc.2024.02.005