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Exploratory Analysis of Lenvatinib Therapy in Patients with Unresectable Hepatocellular Carcinoma Who Have Failed Prior PD−1/PD-L1 Checkpoint Blockade

1
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan
2
Department of Radiology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this manuscript.
Cancers 2020, 12(10), 3048; https://doi.org/10.3390/cancers12103048
Received: 15 September 2020 / Accepted: 8 October 2020 / Published: 20 October 2020
(This article belongs to the Section Cancer Immunology and Immunotherapy)
Programmed cell death protein 1 (PD−1)/PD-ligand 1 (PD-L1) blockade is becoming a novel therapeutic option for a hepatocellular carcinoma. In this work, we evaluated efficacy and safety of lenvatinib following failure of PD-1/PD-L1 blockade. The median progression-free survival was 10 months (95% confidence interval (CI): 8.3–11.8) and the median overall survival was 15.8 months (95% CI: 8.5–23.2) since lenvatinib therapy initiation. The objective response rate was 55.6%, and the disease control rate was 86.1%. All of efficacy outcomes were better than those by lenvatinib treatment alone as the 1st line treatment therapy. No particular safety concerns were observed. It was speculated that lenvatinib right after failure of PD-1/PD-L1 blockade provided synergistic effect since anti-PD-1 antibodies can remain binding to CD8+T cells for more than several months. Lenvatinib demonstrated considerably high antitumor activity and good survival benefit with acceptable toxicity in patients with unresectable HCC when administered right after failure of PD-1/PD-L1 blockade.
Although programmed cell death protein 1 (PD−1)/PD-ligand 1 (PD-L1) blockade is effective in a subset of patients with hepatocellular carcinoma (HCC), its therapeutic response is still unsatisfactory. Alternatively, the potential impact of the lenvatinib in patients who showed tumor progression on PD−1/PD-L1 blockade is unknown. In this work, we evaluated the safety and efficacy of lenvatinib administration after PD-1/PD-L1 checkpoint blockade. The outcome and safety of lenvatinib administered after PD-1/PD-L1 blockade failure was analyzed retrospectively in 36 patients. Tumor growth was assessed every 4–8 weeks using modified Response Evaluation Criteria in Solid Tumors. The mean relative dose intensity of lenvatinib was 87.6% and 77.8% in patients receiving a starting dose of 8 (interquartile range (IQR), 77.5–100.0) mg and 12 (IQR, 64.4–100.0) mg, respectively. Since lenvatinib therapy initiation, the median progression-free survival was 10 months (95% confidence interval (CI): 8.3–11.8) and the median overall survival was 15.8 months (95% CI: 8.5–23.2). The objective response rate was 55.6%, and the disease control rate was 86.1%. No particular safety concerns were observed. Lenvatinib demonstrated considerable antitumor effects with acceptable safety in patients with progressive and unresectable HCC when administered right after PD-1/PD-L1 blockade failure. View Full-Text
Keywords: hepatocellular carcinoma; lenvatinib; PD-1/PD-L1 blockade; molecular targeted agents; vascular endothelial growth factor hepatocellular carcinoma; lenvatinib; PD-1/PD-L1 blockade; molecular targeted agents; vascular endothelial growth factor
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MDPI and ACS Style

Aoki, T.; Kudo, M.; Ueshima, K.; Morita, M.; Chishina, H.; Takita, M.; Hagiwara, S.; Ida, H.; Minami, Y.; Tsurusaki, M.; Nishida, N. Exploratory Analysis of Lenvatinib Therapy in Patients with Unresectable Hepatocellular Carcinoma Who Have Failed Prior PD−1/PD-L1 Checkpoint Blockade. Cancers 2020, 12, 3048.

AMA Style

Aoki T, Kudo M, Ueshima K, Morita M, Chishina H, Takita M, Hagiwara S, Ida H, Minami Y, Tsurusaki M, Nishida N. Exploratory Analysis of Lenvatinib Therapy in Patients with Unresectable Hepatocellular Carcinoma Who Have Failed Prior PD−1/PD-L1 Checkpoint Blockade. Cancers. 2020; 12(10):3048.

Chicago/Turabian Style

Aoki, Tomoko; Kudo, Masatoshi; Ueshima, Kazuomi; Morita, Masahiro; Chishina, Hirokazu; Takita, Masahiro; Hagiwara, Satoru; Ida, Hiroshi; Minami, Yasunori; Tsurusaki, Masakatsu; Nishida, Naoshi. 2020. "Exploratory Analysis of Lenvatinib Therapy in Patients with Unresectable Hepatocellular Carcinoma Who Have Failed Prior PD−1/PD-L1 Checkpoint Blockade" Cancers 12, no. 10: 3048.

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