American Association for Cancer Research
ccr-24-0177_supplementary_figure_s3_suppfs3.pptx (702.88 kB)

Supplementary Figure S3 from Safety and Preliminary Efficacy of Pembrolizumab Following Transarterial Chemoembolization for Hepatocellular Carcinoma: The PETAL Phase Ib Study

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posted on 2024-06-03, 07:23 authored by David J. Pinato, Antonio D'Alessio, Claudia Angela Maria Fulgenzi, Alexandra Emilia Schlaak, Ciro Celsa, Saskia Killmer, Jesus Miguens Blanco, Caroline Ward, Charalampos-Vlasios Stikas, Mark R. Openshaw, Nicole Acuti, Georgios Nteliopoulos, Cristina Balcells, Hector C. Keun, Robert D. Goldin, Paul J. Ross, Alessio Cortellini, Robert Thomas, Anna-Mary Young, Nathan Danckert, Paul Tait, Julian R. Marchesi, Bertram Bengsch, Rohini Sharma

Supplementary Figure S3. Manual gating scheme used for analysis of peripheral immune landscape. Live singlet CD45+ were gated on CD3+CD19- and CD3-CD19+ cells. T cells were further gated on CD4 T cells, CD8 T cells, MAIT cells, gd T cells and NKT cells.


Wellcome Trust (WT)

Fondazione AIRC per la ricerca sul cancro ETS (AIRC)

Roger Williams Foundation for Liver Disease

Cancer Research UK (CRUK)



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 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. 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. TACE plus pembrolizumab was tolerable with no evidence of synergistic toxicity, encouraging further clinical development of immunotherapy alongside TACE.

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