Exploratory Analysis of Lenvatinib Therapy in Patients with Unresectable Hepatocellular Carcinoma Who Have Failed Prior PD-1/PD-L1 Checkpoint Blockade.
Exploratory Analysis of Lenvatinib Therapy in Patients with Unresectable Hepatocellular Carcinoma Who Have Failed Prior PD-1/PD-L1 Checkpoint Blockade.
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lenvatinib治疗的探索性分析是在先前PD-1/PD-L1检查点阻滞之前失败的肝细胞癌患者的探索性分析。
DOI：
10.3390/cancers12103048
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发表时间：
2020-10-20
期刊：
影响因子：
5.2
通讯作者：
Nishida N
中科院分区：
文献类型：
--
作者：
Aoki T;Kudo M;Ueshima K;Morita M;Chishina H;Takita M;Hagiwara S;Ida H;Minami Y;Tsurusaki M;Nishida N
程序性细胞死亡蛋白1（PD-1）/PD-配体1（PD-L1）阻断正在成为肝细胞癌的一种新的治疗选择。在这项工作中，我们评估了乐伐替尼在PD-1/PD-L1阻断失败后的疗效和安全性。自乐伐替尼治疗开始以来，中位无进展生存期为10个月（95%置信区间（CI）：8.3-11.8），中位总生存期为15.8个月（95% CI：8.5-23.2）。客观有效率为55.6%，疾病控制率为86.1%。所有疗效结局均优于乐伐替尼单药作为一线治疗的疗效结局。未观察到特殊的安全性问题。据推测，在PD-1/PD-L1阻断失败后立即使用乐伐替尼可产生协同效应，因为抗PD-1抗体可与CD 8 +T细胞结合数月以上。当在PD-1/PD-L1阻断失败后立即给药时，在不可切除的HCC患者中显示出相当高的抗肿瘤活性和良好的生存获益，毒性可接受。尽管程序性细胞死亡蛋白1（PD-1）/PD-配体1（PD-L1）阻断剂在一部分肝细胞癌（HCC）患者中有效，但其治疗反应仍不令人满意。或者，乐伐替尼对PD−1/PD-L1阻断后肿瘤进展患者的潜在影响尚不清楚。在这项工作中，我们评估了PD-1/PD-L1检查点阻断后乐伐替尼给药的安全性和有效性。在36例患者中回顾性分析了PD-1/PD-L1阻断失败后给予乐伐替尼的结局和安全性。使用改良的实体瘤疗效评价标准，每4-8周评估一次肿瘤生长。在接受8（四分位距（IQR），77.5-100.0）mg和12（IQR，64.4-100.0）mg起始剂量的患者中，乐伐替尼的平均相对剂量强度分别为87.6%和77.8%。自乐伐替尼治疗开始后，中位无进展生存期为10个月（95%置信区间（CI）：8.3-11.8），中位总生存期为15.8个月（95% CI：8.5-23.2）。客观有效率为55.6%，疾病控制率为86.1%。未观察到特殊的安全性问题。在PD-1/PD-L1阻断失败后立即给药时，乐伐替尼在进展性和不可切除的HCC患者中表现出相当大的抗肿瘤作用，且安全性可接受。
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.
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影响因子：
8.8
作者：
Boss, D. S.;Glen, H.;Beijnen, J. H.;Keesen, M.;Morrison, R.;Tait, B.;Copalu, W.;Mazur, A.;Wanders, J.;O'Brien, J. P.;Schellens, J. H. M.;Evans, T. R. J.
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Evans, T. R. J.
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
45.3
作者：
Finn, Richard S.;Ikeda, Masafumi;Llovet, Josep M.
通讯作者：
Llovet, Josep M.
影响因子：
4.4
作者：
Berko, D;Carmi, Y;Gross, G
通讯作者：
Gross, G
影响因子：
158.5
作者：
Finn, Richard S.;Qin, Shukui;Cheng, Ann-Lii
通讯作者：
Cheng, Ann-Lii