Safety and Preliminary Efficacy of Pembrolizumab Following Transarterial Chemoembolization for Hepatocellular Carcinoma: The PETAL Phase Ib Study.

Autor:	Pinato DJ; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.; Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy., D'Alessio A; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.; Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy., Fulgenzi CAM; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom., Schlaak AE; Department of Internal Medicine, University Hospital Freiburg, Freiburg, Germany., Celsa C; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.; Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy., Killmer S; Department of Internal Medicine, University Hospital Freiburg, Freiburg, Germany., Blanco JM; Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, St Mary's Hospital Campus, London, United Kingdom., Ward C; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom., Stikas CV; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom., Openshaw MR; Institute of Cancer and Genomics Sciences, University of Birmingham, Birmingham, United Kingdom., Acuti N; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom., Nteliopoulos G; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom., Balcells C; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom., Keun HC; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom., Goldin RD; Centre for Pathology, Imperial College London, Charing Cross Hospital, London, United Kingdom., Ross PJ; Department of Medical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.; King's College Hospital NHS Foundation Trust, London, United Kingdom., Cortellini A; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.; Division of Medical Oncology, Policlinico Universitario Campus Bio-Medico, Rome, Italy., Thomas R; Interventional Radiology, Imperial College NHS Trust, Hammersmith Hospital, London, United Kingdom., Young AM; Department of Medical Oncology, St Georges University Hospitals, NHS Foundation Trust, St George's University Hospitals NHS Foundation Trust, London, United Kingdom., Danckert N; Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, St Mary's Hospital Campus, London, United Kingdom., Tait P; Interventional Radiology, Imperial College NHS Trust, Hammersmith Hospital, London, United Kingdom., Marchesi JR; Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, St Mary's Hospital Campus, London, United Kingdom., Bengsch B; Department of Internal Medicine, University Hospital Freiburg, Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK), Heidelberg, Germany, partner site Freiburg., Sharma R; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Jun 03; Vol. 30 (11), pp. 2433-2443.
DOI:	10.1158/1078-0432.CCR-24-0177
Abstrakt:	Purpose: Transarterial chemoembolization (TACE) may prime adaptive immunity and enhance immunotherapy efficacy. PETAL evaluated safety, preliminary activity of TACE plus pembrolizumab and explored mechanisms of efficacy. Patients and Methods: Patients with liver-confined hepatocellular carcinoma (HCC) were planned to receive up to two rounds of TACE followed by pembrolizumab 200 mg every 21 days commencing 30 days post-TACE until disease progression or unacceptable toxicity for up to 1 year. Primary endpoint was safety, with assessment window of 21 days from pembrolizumab initiation. Secondary endpoints included progression-free survival (PFS) and evaluation of tumor and host determinants of response. Results: Fifteen patients were included in the safety and efficacy population: 73% had nonviral cirrhosis; median age was 72 years. Child-Pugh class was A in 14 patients. Median tumor size was 4 cm. Ten patients (67%) received pembrolizumab after one TACE; 5 patients after two (33%). Pembrolizumab yielded no synergistic toxicity nor dose-limiting toxicities post-TACE. Treatment-related adverse events occurred in 93% of patients, most commonly skin rash (40%), fatigue, and diarrhea (27%). After a median follow-up of 38.5 months, objective response rate 12 weeks post-TACE was 53%. PFS rate at 12 weeks was 93% and median PFS was 8.95 months [95% confidence interval (CI): 7.30-NE (not estimable)]. Median duration of response was 7.3 months (95% CI: 6.3-8.3). Median overall survival was 33.5 months (95% CI: 11.6-NE). Dynamic changes in peripheral T-cell subsets, circulating tumor DNA, serum metabolites, and in stool bacterial profiles highlight potential mechanisms of action of multimodal therapy. Conclusions: TACE plus pembrolizumab was tolerable with no evidence of synergistic toxicity, encouraging further clinical development of immunotherapy alongside TACE. (©2024 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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