Journal
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Volume 148, Issue 8, Pages 2115-2125Publisher
SPRINGER
DOI: 10.1007/s00432-021-03767-4
Keywords
Pembrolizumab; Transarterial chemoembolization; Lenvatinib; Hepatectomy; Hepatocellular carcinoma; Conversion
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This retrospective study compared the clinical outcomes of pembrolizumab-lenvatinib-TACE and lenvatinib-TACE sequential therapy in Chinese uHCC patients with initial PD-L1 expression, indicating that the former had a higher conversion rate, longer OS and PFS.
Purpose The aim of this retrospective study was to compare the clinical outcomes of pembrolizumab-lenvatinib-transarterial chemoembolization (TACE) versus lenvatinib-TACE sequential therapy in selected populations of Chinese patients with initially unresectable hepatocellular carcinoma (uHCC) harbouring programmed cell death ligand-1 (PD-L1) expression. Methods Consecutive patients with initial PD-L1-positive uHCC who received pembrolizumab-lenvatinib-TACE or lenvatinib-TACE sequential therapy were retrospectively identified from three medical institutions during 2016-2020. The primary endpoints included the rate of conversion therapy, defined as converting initially uHCC to hepatectomy, overall survival (OS), and progression-free survival (PFS); secondary endpoint was the frequency of key adverse events (AEs). Results In total, 220 consecutively recruited patients were retrospectively reviewed, 78 of whom were ineligible according to the current criteria, leaving 142 patients [pembrolizumab-lenvatinib-TACE: n = 70, median age 58 years (range 36-69) and lenvatinib-TACE: n = 72, 57 years (35-68)] who were eligible for the study. The median duration of follow-up was 27 months [95% confidence interval (CI), 26.3-28.7 months]. At the last follow-up, the rate of conversion therapy was 25.7% in the pembrolizumab-lenvatinib-TACE group and 11.1% in the lenvatinib-TACE group (p = 0.025). The median OS was 18.1 months (95% CI 16.5-20.7) in the pembrolizumab-lenvatinib-TACE group versus 14.1 months (95% CI 12.2-16.9) in the lenvatinib-TACE group [hazard ratio (HR) 0.56, 95% CI 0.38-0.83; p = 0.004]. A distinct difference in the median PFS interval between the groups was detected [9.2 months (95% CI 7.1-10.4) in the pembrolizumab-lenvatinib-TACE group vs. 5.5 months (95% CI 3.9-6.6) in the lenvatinib-TACE group (HR 0.60; 95% CI 0.39-0.91; p = 0.006)]. The rates of the key AEs assessed, which were hypertension, nausea, and rash, were higher in the pembrolizumab-lenvatinib-TACE group than in the lenvatinib-TACE group (all p < 0.05). Conclusion Among the selected populations of patients with initial PD-L1-positive uHCC, pembrolizumab-lenvatinib-TACE sequential therapy may have promising antitumour activity, with an acceptable conversion rate and a well-characterized safety profile.
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