Abstract
A substantial proportion of patients with hepatocellular carcinoma have to face up,
sooner or later, to systemic therapy. The current standards as first line systemic
therapies are either atezolizumab (anti-PD-L1) plus bevacizumab (anti-VEGF), or durvalumab
(anti-PD-L1) plus tremelimumab (anti-CTLA-4). However, the median overall survival
remains below 20 months, and a minority of patients become long-term survivors. Of
interest in immune-oncology strategies for hepatocellular carcinoma, the objective
response seems to be the most reliable surrogate marker of better overall survival.
TRIPLET-HCC (NCT05665348) is a multicentre, randomised, open-label phase II-III trial
designed to evaluate efficacy and safety of the triple combination by the addition
of ipilimumab (anti-CTLA-4) to atezolizumab/bevacizumab, versus the double atezolizumab/bevacizumab
combination. The main inclusion criteria are histologically proven BCLC-B/C HCC without
previous systemic therapy. The primary objective of the phase II is the objective
response rate in the triple arm, and OS in the triple versus double arms in the phase
III. Secondary endpoints common to the phases II and III are the comparisons of progression-free
survival, objective response rates, tolerance and quality of life. In addition, genetic
and epigenetic studies from tissue and circulating DNA/RNA will be conducted to assess
their prognostic or predictive value.
Keywords
Abbreviations:
CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), DCR (disease control rate), DOR (duration of response), DSMB (data safety monitoring board), EHS (extra-hepatic spread), HCC (hepatocellular carcinoma), IO (immuno-oncology), ICI (immune-checkpoint inhibitors), irAE (immune-related adverse event), MIV (macrovascular invasion), mITT (modified intention-to-treat), ORR (objective response rate), OS (overall survival), PFS (progression-free survival), PD-L1 (Programmed death-ligand 1), PD-1 (Programmed cell Death protein 1), TKI (tyrosine kinase inhibitor), TTR (time to response), TTP (time to progression), TRAE (treatment-related adverse event), VEGF (Vascular Endothelial Growth Factor)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: February 16, 2023
Accepted:
January 27,
2023
Received:
January 21,
2023
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
