Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non–Small-Cell Lung Cancer After Previous Systemic Treatment Failure—A Retrospective Study
BackgroundPre-clinical and clinical evidences support that simultaneous blockade of programmed death-1 (PD-1) and vascular endothelial growth factor receptor (VEGFR) can enhance antigen-specific T-cell migration, and show tolerable toxicity with favorable antitumor activity in patients. In this stud...
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.628124/full |
| _version_ | 1818619148444368896 |
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| author | Peiliang Wang Peiliang Wang Xiaozhuang Fang Xiaozhuang Fang Tianwen Yin Tianwen Yin Hairong Tian Hairong Tian Jinming Yu Jinming Yu Feifei Teng Feifei Teng |
| author_facet | Peiliang Wang Peiliang Wang Xiaozhuang Fang Xiaozhuang Fang Tianwen Yin Tianwen Yin Hairong Tian Hairong Tian Jinming Yu Jinming Yu Feifei Teng Feifei Teng |
| author_sort | Peiliang Wang |
| collection | DOAJ |
| description | BackgroundPre-clinical and clinical evidences support that simultaneous blockade of programmed death-1 (PD-1) and vascular endothelial growth factor receptor (VEGFR) can enhance antigen-specific T-cell migration, and show tolerable toxicity with favorable antitumor activity in patients. In this study, we aimed to assess the safety and efficacy of anlotinib, a novel multitarget tyrosine kinase inhibitor for VEGFR, platelet-derived growth receptor (PDGFR), and the stem cell-factor receptor (c-Kit), combined with anti-PD-1 treatment in patients with advanced NSCLC.MethodsSixty-seven patients with previously treated advanced NSCLC receiving anti-PD-1 agents concomitant with anlotinib were retrospectively enrolled in an IRB approved study. Anti-PD-1 agents including pembrolizumab, nivolumab, camrelizumab, toripalimab, sintilimab, and tislelizumab were administered every two or three weeks until disease progression or unacceptable toxicity was reached. Anlotinib was administered orally once daily on days 1–14 of a 21-day cycle. The safety and tolerability of the combination treatment were assessed by the incidence of adverse events. The efficacy of the treatment was assessed by the tumor response and survival.ResultsWith a median follow-up period of 8.7 months, treatment-related adverse events occurred in 85% (57/67) of patients and grade 3–4 adverse events were observed in 27 patients (40%). No unexpected adverse events or significantly increased toxicities were observed. Complete response was not observed, 19 patients had partial response (28.4%), 39 had stable disease (58.2%) and 9 had progressive disease (13.4%). The overall response (ORR) and disease control rates (DCR) were 28.4% and 86.6%, respectively. The median progression-free survival (PFS) was 6.9 months (95% CI, 5.5-8.3 months) and overall survival (OS) was 14.5 months (95% CI, 10.9-18.1 months). The benefit of anti-PD-1 plus anlotinib was also observed in patients with EGFR mutation positive, liver metastases and brain metastases.ConclusionAnti-PD-1 treatment concomitant with anlotinib has tolerable toxicity and favorable antitumor activity in patients with previously treated advanced NSCLC. Our results add to the growing evidence that supports the benefits of combining immunotherapy with antiangiogenic drugs. This combination could be further evaluated with or without chemotherapy, since no additional toxicity was observed in the combination treatment. |
| first_indexed | 2024-12-16T17:32:53Z |
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| language | English |
| last_indexed | 2024-12-16T17:32:53Z |
| publishDate | 2021-03-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-17799ffe3660403a86905eb65e9b70022022-12-21T22:22:52ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-03-011110.3389/fonc.2021.628124628124Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non–Small-Cell Lung Cancer After Previous Systemic Treatment Failure—A Retrospective StudyPeiliang Wang0Peiliang Wang1Xiaozhuang Fang2Xiaozhuang Fang3Tianwen Yin4Tianwen Yin5Hairong Tian6Hairong Tian7Jinming Yu8Jinming Yu9Feifei Teng10Feifei Teng11Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaBackgroundPre-clinical and clinical evidences support that simultaneous blockade of programmed death-1 (PD-1) and vascular endothelial growth factor receptor (VEGFR) can enhance antigen-specific T-cell migration, and show tolerable toxicity with favorable antitumor activity in patients. In this study, we aimed to assess the safety and efficacy of anlotinib, a novel multitarget tyrosine kinase inhibitor for VEGFR, platelet-derived growth receptor (PDGFR), and the stem cell-factor receptor (c-Kit), combined with anti-PD-1 treatment in patients with advanced NSCLC.MethodsSixty-seven patients with previously treated advanced NSCLC receiving anti-PD-1 agents concomitant with anlotinib were retrospectively enrolled in an IRB approved study. Anti-PD-1 agents including pembrolizumab, nivolumab, camrelizumab, toripalimab, sintilimab, and tislelizumab were administered every two or three weeks until disease progression or unacceptable toxicity was reached. Anlotinib was administered orally once daily on days 1–14 of a 21-day cycle. The safety and tolerability of the combination treatment were assessed by the incidence of adverse events. The efficacy of the treatment was assessed by the tumor response and survival.ResultsWith a median follow-up period of 8.7 months, treatment-related adverse events occurred in 85% (57/67) of patients and grade 3–4 adverse events were observed in 27 patients (40%). No unexpected adverse events or significantly increased toxicities were observed. Complete response was not observed, 19 patients had partial response (28.4%), 39 had stable disease (58.2%) and 9 had progressive disease (13.4%). The overall response (ORR) and disease control rates (DCR) were 28.4% and 86.6%, respectively. The median progression-free survival (PFS) was 6.9 months (95% CI, 5.5-8.3 months) and overall survival (OS) was 14.5 months (95% CI, 10.9-18.1 months). The benefit of anti-PD-1 plus anlotinib was also observed in patients with EGFR mutation positive, liver metastases and brain metastases.ConclusionAnti-PD-1 treatment concomitant with anlotinib has tolerable toxicity and favorable antitumor activity in patients with previously treated advanced NSCLC. Our results add to the growing evidence that supports the benefits of combining immunotherapy with antiangiogenic drugs. This combination could be further evaluated with or without chemotherapy, since no additional toxicity was observed in the combination treatment.https://www.frontiersin.org/articles/10.3389/fonc.2021.628124/fullanlotinibanti-PD-1non–small cell lung cancercombination therapyimmune checkpoint inhibitors |
| spellingShingle | Peiliang Wang Peiliang Wang Xiaozhuang Fang Xiaozhuang Fang Tianwen Yin Tianwen Yin Hairong Tian Hairong Tian Jinming Yu Jinming Yu Feifei Teng Feifei Teng Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non–Small-Cell Lung Cancer After Previous Systemic Treatment Failure—A Retrospective Study Frontiers in Oncology anlotinib anti-PD-1 non–small cell lung cancer combination therapy immune checkpoint inhibitors |
| title | Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non–Small-Cell Lung Cancer After Previous Systemic Treatment Failure—A Retrospective Study |
| title_full | Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non–Small-Cell Lung Cancer After Previous Systemic Treatment Failure—A Retrospective Study |
| title_fullStr | Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non–Small-Cell Lung Cancer After Previous Systemic Treatment Failure—A Retrospective Study |
| title_full_unstemmed | Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non–Small-Cell Lung Cancer After Previous Systemic Treatment Failure—A Retrospective Study |
| title_short | Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non–Small-Cell Lung Cancer After Previous Systemic Treatment Failure—A Retrospective Study |
| title_sort | efficacy and safety of anti pd 1 plus anlotinib in patients with advanced non small cell lung cancer after previous systemic treatment failure a retrospective study |
| topic | anlotinib anti-PD-1 non–small cell lung cancer combination therapy immune checkpoint inhibitors |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.628124/full |
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