Jianzhen Lin1, Xu Yang1, Junyu Long1, Songhui Zhao2, Jinzhu Mao1, Dongxu Wang1, Yi Bai1, Jin Bian1, Lei Zhang1, Xiaobo Yang1, Anqiang Wang3, Fucun Xie1, Weiwei Shi2, Huayu Yang1, Jie Pan4, Ke Hu5, Mei Guan6, Lin Zhao6, Li Huo7, Yilei Mao1, Xinting Sang1, Kai Wang2, Haitao Zhao1. 1. Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing 100730, China. 2. OrigiMed, Shanghai 200135, China. 3. Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China. 4. Department of Radiology, Peking Union Medical College Hospital, Beijing 100730, China. 5. Center of Radiotherapy, Peking Union Medical College Hospital, Beijing 100730, China. 6. Department of Medical Oncology, Peking Union Medical College Hospital, Beijing 100730, China. 7. Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing 100730, China.
Abstract
BACKGROUND: A therapeutic strategy involving combined treatment with lenvatinib plus pembrolizumab (LEP) has demonstrated a relatively high antitumor response in several solid tumors; however, the efficacy and safety of LEP in patients with refractory bile tract carcinoma (BTC) remains unknown. METHODS: This is a single-arm study for a preliminary assessment of the efficacy and tolerability of LEP in patients who experienced progression from prior systemic treatments. Pre-treatment tumor tissues were collected to retrospectively evaluate the expression status of PDL1. RESULTS: Thirty-two patients received second-line and above treatment with LEP. Overall, the objective response rate (ORR) was 25%, the disease control rate (DCR) was 78.1%, and the clinical benefit rate (CBR) was 40.5%. The median progression-free survival (PFS) was 4.9 months (95% CI: 4.7-5.2 months), and the median overall survival (OS) was 11.0 months (95% CI: 9.6-12.3 months). For tolerability, no grade 5 serious adverse events (AEs) were reported. All patients had any-grade AEs, and 59.3% of the patients experienced grade 3 AEs, while only 1 patient experienced a grade 4 AE of stomach bleeding. Fatigue was the most common AE, followed by hypertension and elevated aminotransferase levels. Retrospective analysis for PDL1 expression revealed that PDL1 positive tumor cells were associated with improved clinical benefits and survival outcomes. CONCLUSIONS: LEP is a promising alternative as a non-first-line therapeutic regimen for patients with refractory BTC. Furthermore, well-designed prospective clinical trials with a control arm are still needed to obtain more evidences to confirm the efficacy and safety of this particular regimen as well as the role of PDL1 expression. 2020 Hepatobiliary Surgery and Nutrition. All rights reserved.
BACKGROUND: A therapeutic strategy involving combined treatment with lenvatinib plus pembrolizumab (LEP) has demonstrated a relatively high antitumor response in several solid tumors; however, the efficacy and safety of LEP in patients with refractory bile tract carcinoma (BTC) remains unknown. METHODS: This is a single-arm study for a preliminary assessment of the efficacy and tolerability of LEP in patients who experienced progression from prior systemic treatments. Pre-treatment tumor tissues were collected to retrospectively evaluate the expression status of PDL1. RESULTS: Thirty-two patients received second-line and above treatment with LEP. Overall, the objective response rate (ORR) was 25%, the disease control rate (DCR) was 78.1%, and the clinical benefit rate (CBR) was 40.5%. The median progression-free survival (PFS) was 4.9 months (95% CI: 4.7-5.2 months), and the median overall survival (OS) was 11.0 months (95% CI: 9.6-12.3 months). For tolerability, no grade 5 serious adverse events (AEs) were reported. All patients had any-grade AEs, and 59.3% of the patients experienced grade 3 AEs, while only 1 patient experienced a grade 4 AE of stomach bleeding. Fatigue was the most common AE, followed by hypertension and elevated aminotransferase levels. Retrospective analysis for PDL1 expression revealed that PDL1 positive tumor cells were associated with improved clinical benefits and survival outcomes. CONCLUSIONS: LEP is a promising alternative as a non-first-line therapeutic regimen for patients with refractory BTC. Furthermore, well-designed prospective clinical trials with a control arm are still needed to obtain more evidences to confirm the efficacy and safety of this particular regimen as well as the role of PDL1 expression. 2020 Hepatobiliary Surgery and Nutrition. All rights reserved.
Entities:
Keywords:
PD1; PDL1; Pembrolizumab; bile tract cancer; lenvatinib
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