Ablation Reboots the Response in Advanced Hepatocellular Carcinoma With Stable or Atypical Response During PD-1 Therapy: A Proof-of-Concept Study
Background: The anti-programmed cell death protein-1 (PD-1) inhibitor is one of the second-line therapies for advanced hepatocellular carcinoma (HCC) after sorafenib failure. The goal of this study is to evaluate the feasibility and safety of ablation on the tumor in patients with advanced HCC who h...
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| Format: | Article |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.580241/full |
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| author | Ning Lyu Yanan Kong Xiaoxian Li Luwen Mu Haijing Deng Huiming Chen Meng He Jinfa Lai Jibin Li Hailin Tang Youen Lin Ming Zhao |
| author_facet | Ning Lyu Yanan Kong Xiaoxian Li Luwen Mu Haijing Deng Huiming Chen Meng He Jinfa Lai Jibin Li Hailin Tang Youen Lin Ming Zhao |
| author_sort | Ning Lyu |
| collection | DOAJ |
| description | Background: The anti-programmed cell death protein-1 (PD-1) inhibitor is one of the second-line therapies for advanced hepatocellular carcinoma (HCC) after sorafenib failure. The goal of this study is to evaluate the feasibility and safety of ablation on the tumor in patients with advanced HCC who had stable disease or atypical response during single anti-PD-1 therapy after sorafenib failure. Atypical response defined as mixed responses in different lesions of the same individual (e.g., active or stable lesions mixed with progressive lesions).Patients and Methods: This proof-of-concept clinical trial enrolled 50 patients treated with an anti-PD-1 inhibitor of nivolumab or pembrolizumab monotherapy between July 2015 and Nov 2017. Thirty-three cases with stable disease or atypical response to anti-PD-1 inhibitor received subtotal thermal ablation. The safety and the response of ablation during anti-PD-1 therapy were evaluated. The survival was estimated by the Kaplan-Meier curve.Results: Of all 50 patients treated with anti-PD-1 therapy, the rate of response, stable disease, atypical and typical progression were 10% (n = 5), 42% (n = 21) 32% (n = 16), and 12% (n = 6), respectively. Additional ablation improved efficacy with tolerable toxicity, and the response rate was increased from 10 to 24% (12/50). The median time to progression, progression-free survival, and overall survival was 6.1 months (95%CI, 2.6–11.2), 5 months (95%CI, 2.9–7.1), and 16.9 months (95%CI, 7.7–26.1), respectively.Conclusions: This proof-of-concept trial suggested that additional ablation may increase the objective response rate with tolerated toxicity and achieved a relatively better median survival, in advanced HCC patients who had stable or atypical progressive diseases during anti-PD-1 therapy, which may provide a potentially promising strategy to treat advanced HCC.Trial registration number:ClinicalTrials.gov identifier: NCT03939975. |
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| id | doaj.art-c09ab4b3db85451eac3f5c3e76cc6d98 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T21:32:41Z |
| publishDate | 2020-10-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-c09ab4b3db85451eac3f5c3e76cc6d982022-12-21T19:26:01ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-10-011010.3389/fonc.2020.580241580241Ablation Reboots the Response in Advanced Hepatocellular Carcinoma With Stable or Atypical Response During PD-1 Therapy: A Proof-of-Concept StudyNing Lyu0Yanan Kong1Xiaoxian Li2Luwen Mu3Haijing Deng4Huiming Chen5Meng He6Jinfa Lai7Jibin Li8Hailin Tang9Youen Lin10Ming Zhao11Liver Cancer Study and Service Group, Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Department of Breast Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaZhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaDepartment of Vascular Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaLiver Cancer Study and Service Group, Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaLiver Cancer Study and Service Group, Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaLiver Cancer Study and Service Group, Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaLiver Cancer Study and Service Group, Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Clinical Research, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Interventional Radiology, Jieyang Affiliated Hospital, Sun Yat-sen University, Jieyang, ChinaLiver Cancer Study and Service Group, Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaBackground: The anti-programmed cell death protein-1 (PD-1) inhibitor is one of the second-line therapies for advanced hepatocellular carcinoma (HCC) after sorafenib failure. The goal of this study is to evaluate the feasibility and safety of ablation on the tumor in patients with advanced HCC who had stable disease or atypical response during single anti-PD-1 therapy after sorafenib failure. Atypical response defined as mixed responses in different lesions of the same individual (e.g., active or stable lesions mixed with progressive lesions).Patients and Methods: This proof-of-concept clinical trial enrolled 50 patients treated with an anti-PD-1 inhibitor of nivolumab or pembrolizumab monotherapy between July 2015 and Nov 2017. Thirty-three cases with stable disease or atypical response to anti-PD-1 inhibitor received subtotal thermal ablation. The safety and the response of ablation during anti-PD-1 therapy were evaluated. The survival was estimated by the Kaplan-Meier curve.Results: Of all 50 patients treated with anti-PD-1 therapy, the rate of response, stable disease, atypical and typical progression were 10% (n = 5), 42% (n = 21) 32% (n = 16), and 12% (n = 6), respectively. Additional ablation improved efficacy with tolerable toxicity, and the response rate was increased from 10 to 24% (12/50). The median time to progression, progression-free survival, and overall survival was 6.1 months (95%CI, 2.6–11.2), 5 months (95%CI, 2.9–7.1), and 16.9 months (95%CI, 7.7–26.1), respectively.Conclusions: This proof-of-concept trial suggested that additional ablation may increase the objective response rate with tolerated toxicity and achieved a relatively better median survival, in advanced HCC patients who had stable or atypical progressive diseases during anti-PD-1 therapy, which may provide a potentially promising strategy to treat advanced HCC.Trial registration number:ClinicalTrials.gov identifier: NCT03939975.https://www.frontiersin.org/article/10.3389/fonc.2020.580241/fullhepatocellular carcinomaanti-PD-1 mAbsthermal ablationnivolumabpembrolizumab |
| spellingShingle | Ning Lyu Yanan Kong Xiaoxian Li Luwen Mu Haijing Deng Huiming Chen Meng He Jinfa Lai Jibin Li Hailin Tang Youen Lin Ming Zhao Ablation Reboots the Response in Advanced Hepatocellular Carcinoma With Stable or Atypical Response During PD-1 Therapy: A Proof-of-Concept Study Frontiers in Oncology hepatocellular carcinoma anti-PD-1 mAbs thermal ablation nivolumab pembrolizumab |
| title | Ablation Reboots the Response in Advanced Hepatocellular Carcinoma With Stable or Atypical Response During PD-1 Therapy: A Proof-of-Concept Study |
| title_full | Ablation Reboots the Response in Advanced Hepatocellular Carcinoma With Stable or Atypical Response During PD-1 Therapy: A Proof-of-Concept Study |
| title_fullStr | Ablation Reboots the Response in Advanced Hepatocellular Carcinoma With Stable or Atypical Response During PD-1 Therapy: A Proof-of-Concept Study |
| title_full_unstemmed | Ablation Reboots the Response in Advanced Hepatocellular Carcinoma With Stable or Atypical Response During PD-1 Therapy: A Proof-of-Concept Study |
| title_short | Ablation Reboots the Response in Advanced Hepatocellular Carcinoma With Stable or Atypical Response During PD-1 Therapy: A Proof-of-Concept Study |
| title_sort | ablation reboots the response in advanced hepatocellular carcinoma with stable or atypical response during pd 1 therapy a proof of concept study |
| topic | hepatocellular carcinoma anti-PD-1 mAbs thermal ablation nivolumab pembrolizumab |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.580241/full |
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