Safety and preliminary efficacy of pembrolizumab following trans-arterial chemoembolization for hepatocellular carcinoma: the PETAL phase Ib study

Pinato, David J., D'Alessio, Antonio, Fulgenzi, Claudia Angela Maria., Schlaak, Alexandra Emilia, Celsa, Ciro, Killmer, Saskia, Blanco, Jesus Miguens., Ward, Caroline, Stikas, Charalampos-Vlasios, Openshaw, Mark R., Acuti, Nicole, Nteliopoulos, Georgios, Balcells, Cristina, Keun, Hector C., Goldin, Robert D., Ross, Paul J., Cortellini, Alessio, Thomas, Robert, Young, Anna Mary., Danckert, Nathan, Tait, Paul, Marchesi, Julian R. ORCID: https://orcid.org/0000-0002-7994-5239, Bengsch, Bertram and Sharma, Rohini 2024. Safety and preliminary efficacy of pembrolizumab following trans-arterial chemoembolization for hepatocellular carcinoma: the PETAL phase Ib study. Clinical Cancer Research 30 (11) , pp. 2433-2443. 10.1158/1078-0432.CCR-24-0177

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	American Association for Cancer Research
ISSN:	1078-0432
Date of First Compliant Deposit:	7 May 2024
Date of Acceptance:	3 April 2024
Last Modified:	08 Jul 2024 10:24
URI:	https://orca.cardiff.ac.uk/id/eprint/168746

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