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Initial clinical experience with durvalumab plus tremelimumab in patients with unresectable hepatocellular carcinoma in real‑world practice.

ABSTRACT: Although durvalumab plus tremelimumab (Dur/Tre) has been approved as first-line therapy for patients with unresectable hepatocellular carcinoma (u-HCC), its outcomes in real-world clinical practice are unclear. The present study aimed to evaluate the efficacy and safety of Dur/Tre treatment. This multicenter study was conducted between March 2023 and January 2024, and included 120 patients with u-HCC treated with Dur/Tre. Among the patients, 44 had no history of systemic treatment. Progression-free survival (PFS), therapeutic response and adverse events (AEs) were assessed. The objective response rate (ORR) and disease control rates (DCR) were 15.8 and 53.3%, respectively. The median PFS was 3.9 months. The incidence rates of AEs of any grade and those grade 3 or higher were 83.3 and 36.7%, respectively. Liver injury was the most frequent AE of any grade and grade 3 or higher. Although there was no significant difference in ORR and PFS between the first and later line groups (ORR 15.8 vs. 15.7%, P=0.986; PFS 4.5 vs. 3.6 months, P=0.213), there was a significant difference in DCR between the two groups (65.8 vs. 45.9%, P=0.034). No significant differences were noted between the first- and later-line treatment groups regarding the incidence rate of AEs. Decision tree analysis revealed that poor liver function and advanced age were significant variables for discontinuation owing to AEs. In conclusion, Dur/Tre as first-line therapy had better disease control responses compared with later-line therapy; however, this regimen should be carefully administered to patients with deteriorating hepatic function or advanced age.

SUBMITTER: Shimose S

PROVIDER: S-EPMC11228928 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Initial clinical experience with durvalumab plus tremelimumab in patients with unresectable hepatocellular carcinoma in real‑world practice.

Shimose Shigeo S Saeki Issei I Tomonari Tetsu T Ito Takanori T Tani Joji J Takeuchi Yasuto Y Yoshioka Naoki N Naito Takehito T Takeuchi Mamiko M Kakizaki Satoru S Hatanaka Takeshi T Sasaki Kyo K Yasunaka Tetsuya T Sakata Masahiro M Iwamoto Hideki H Itano Satoshi S Shirono Tomotake T Tanabe Norikazu N Yamamoto Takafumi T Naganuma Atsushi A Nishina Soji S Otsuka Motoyuki M Kawashima Hiroki H Takayama Tetsuji T Takami Taro T Kawaguchi Takumi T

Oncology letters 20240625 2

Although durvalumab plus tremelimumab (Dur/Tre) has been approved as first-line therapy for patients with unresectable hepatocellular carcinoma (u-HCC), its outcomes in real-world clinical practice are unclear. The present study aimed to evaluate the efficacy and safety of Dur/Tre treatment. This multicenter study was conducted between March 2023 and January 2024, and included 120 patients with u-HCC treated with Dur/Tre. Among the patients, 44 had no history of systemic treatment. Progression-f ...[more]

PMID: 38979550

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Project description:PurposeThis phase I/II study evaluated tremelimumab (anticytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody) and durvalumab (antiprogrammed death ligand-1 monoclonal antibody) as monotherapies and in combination for patients with unresectable hepatocellular carcinoma (HCC), including a novel regimen featuring a single, priming dose of tremelimumab (ClinicalTrials.gov identifier: NCT02519348).Patients and methodsPatients with HCC who had progressed on, were intolerant to, or refused sorafenib were randomly assigned to receive T300 + D (tremelimumab 300 mg plus durvalumab 1,500 mg [one dose each during the first cycle] followed by durvalumab 1,500 mg once every 4 weeks), durvalumab monotherapy (1,500 mg once every 4 weeks), tremelimumab monotherapy (750 mg once every 4 weeks [seven doses] and then once every 12 weeks), or T75 + D (tremelimumab 75 mg once every 4 weeks plus durvalumab 1,500 mg once every 4 weeks [four doses] followed by durvalumab 1,500 mg once every 4 weeks). Safety was the primary end point. Secondary end points included objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors v1.1 and overall survival; exploratory end points included circulating lymphocyte profiles.ResultsA total of 332 patients were enrolled (T300 + D, n = 75; durvalumab, n = 104; tremelimumab, n = 69; and T75 + D, n = 84). Tolerability was acceptable across arms, with grade ≥ 3 treatment-related adverse events occurring in 37.8%, 20.8%, 43.5%, and 24.4%, respectively. Confirmed ORRs (95% CI) were 24.0% (14.9 to 35.3), 10.6% (5.4 to 18.1), 7.2% (2.4 to 16.1), and 9.5% (4.2 to 17.9), respectively. An early expansion of CD8+ lymphocytes was associated with response across arms, with highest proliferating CD8+ lymphocyte levels occurring in the T300 + D arm. The median (95% CI) overall survival was 18.7 (10.8 to 27.3), 13.6 (8.7 to 17.6), 15.1 (11.3 to 20.5), and 11.3 (8.4 to 15.0) months in the T300 + D, durvalumab, tremelimumab, and T75 + D arms, respectively.ConclusionAll regimens were found to be tolerable and clinically active; however, the T300 + D regimen demonstrated the most encouraging benefit-risk profile. The unique pharmacodynamic activity and association with ORR of the T300 + D regimen further support its continued evaluation in HCC.

Project description:BackgroundThis study aimed to evaluate safety and efficacy of programmed death-1 (PD-1) inhibitor sintilimab plus tyrosine kinase inhibitors (TKI) in a real-word cohort of patients with unresectable hepatocellular carcinoma (uHCC).MethodsA total of 60 patients treated with sintilimab plus TKI between February 2019 and December 2019 were enrolled. Radiological response was recorded by computed tomography (CT) or magnetic resonance imaging (MRI) at baseline and every 6-12 weeks after treatment initiation. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and HCC-specific modified RECIST (mRECIST).ResultsAs of the data cutoff on September 30st, 2020, the median duration of follow-up was 10.4 (4.3-23.9) months. The objective response rate (ORR) and disease control rate (DCR) were 36.7% (95% CI: 24.9-48.5%), 81.7% (95% CI: 71.9-91.5%) according to the RECIST 1.1, and 52.8% (95% CI: 39.1-66.5%), 83.0% (95% CI: 73.2-93.8%) according to mRECIST criteria. Among 36 HCC patients with multinodular HCC or locally-advanced HCC with portal vein tumor thrombus (PVTT), 14 patients received one session of transarterial chemoembolization (TACE) within 1 month before or after the combinational systemic therapies, and the rest 22 patients did not receive any local regional therapies. After propensity score matching, patients from the TACE group tended to have a longer PFS (median, 10.1 vs. 9.1 months, P=0.73) than those from the non-TACE group but without significant differences. A total of 8 patients received surgical resection after the combined systemic therapies and 3 patients achieved pathological CR. No recurrence or metastasis was observed in 6 patients. A total of 46 (76.7%) patients reported adverse event (AE) with any grade and 8 (13.3%) patients discontinued the combination therapy due to grade 3/4 severe adverse events.ConclusionsPD-1-targeted immunotherapy sintilimab plus TKIs exhibited promising efficacy with tolerable toxicity in unresectable HCC. The addition of TACE to the combined systemic therapies also resulted in a favorable tumor control and safety. For select responders, surgical resection might be a choice for radical treatment.

Dataset Information

Initial clinical experience with durvalumab plus tremelimumab in patients with unresectable hepatocellular carcinoma in real‑world practice.

Publications

Initial clinical experience with durvalumab plus tremelimumab in patients with unresectable hepatocellular carcinoma in real‑world practice.

Similar Datasets

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