Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study
PurposeImmune checkpoint inhibitors plus antiangiogenic tyrosine kinase inhibitors may offer a first-line treatment for advanced hepatocellular carcinoma (HCC). In this phase 2 trial [registered with clinicaltrials.gov (NCT04052152)], we investigated the safety and efficacy of first-line anti-PD-1 a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.909035/full |
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| author | Xiaofeng Chen Xiaofeng Chen Wei Li Xiaofeng Wu Fengjiao Zhao Deqiang Wang Hao Wu Yanhong Gu Xiao Li Xiaofeng Qian Jun Hu Changxian Li Yongxiang Xia Jianhua Rao Xinzheng Dai Qianwen Shao Jie Tang Xiangcheng Li Yongqian Shu |
| author_facet | Xiaofeng Chen Xiaofeng Chen Wei Li Xiaofeng Wu Fengjiao Zhao Deqiang Wang Hao Wu Yanhong Gu Xiao Li Xiaofeng Qian Jun Hu Changxian Li Yongxiang Xia Jianhua Rao Xinzheng Dai Qianwen Shao Jie Tang Xiangcheng Li Yongqian Shu |
| author_sort | Xiaofeng Chen |
| collection | DOAJ |
| description | PurposeImmune checkpoint inhibitors plus antiangiogenic tyrosine kinase inhibitors may offer a first-line treatment for advanced hepatocellular carcinoma (HCC). In this phase 2 trial [registered with clinicaltrials.gov (NCT04052152)], we investigated the safety and efficacy of first-line anti-PD-1 antibody sintilimab plus antiangiogenic TKI anlotinib for advanced HCC.Methods and MaterialsPathologically-proven advanced HCC patients received sintilimab (200 mg) on day 1 and anlotinib (12 mg) once daily on days 1 to 14 every 3 weeks, with a safety run-in for the first six participants to assess dose-limiting toxicities (DLTs). The primary endpoints were safety and objective response rate (ORR) per RECIST v1.1.ResultsTwenty advanced HCC patients were enrolled. No DLTs occurred in the safety run-in. All patients had treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 8 (40.0%) patients, the most common being decreased platelet count (10.0%) and increased γ-glutamyl transferase (10.0%). No grade 4/5 TRAEs occurred. Five (25%) patients developed immune-related AEs. The ORR was 35.0% (95%CI 15.4%-59.2%) per RECIST v1.1 and 55.0% (95%CI 31.5%-76.9%) per modified RECIST. At data cutoff (March 31, 2021), the median progression-free survival was 12.2 months (95%CI, 3.8 to not reached). The median PFS was significantly longer in patients with lower LDH levels (not reached [NR], 95% CI, 8.7 to NR vs. higher LDH levels 5.2 months, 95% CI 3.4 to NR; P=0.020) and a CONUT score ≤2 (NR, 95% CI 5.1 to NR vs. CONUT score >2 6.2 months, 95% CI 1.8 to NR; P=0.020). Furthermore, patients showing tumor response had a significantly higher median proportion of CD16+CD56+ NK cells than patients who had stable or progressive disease (21.6% vs. 14.6%; P=0.026).ConclusionSintilimab plus anlotinib showed promising clinical activities with manageable toxicity as first-line treatment of advanced HCC. |
| first_indexed | 2024-04-14T05:06:13Z |
| format | Article |
| id | doaj.art-3d3e0352aca84ad7b3302092c6d567ec |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-14T05:06:13Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-3d3e0352aca84ad7b3302092c6d567ec2022-12-22T02:10:41ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-05-011210.3389/fonc.2022.909035909035Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 StudyXiaofeng Chen0Xiaofeng Chen1Wei Li2Xiaofeng Wu3Fengjiao Zhao4Deqiang Wang5Hao Wu6Yanhong Gu7Xiao Li8Xiaofeng Qian9Jun Hu10Changxian Li11Yongxiang Xia12Jianhua Rao13Xinzheng Dai14Qianwen Shao15Jie Tang16Xiangcheng Li17Yongqian Shu18Department of Oncology, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, Pukou Branch of Jiangsu People’s Hospital, Nanjing, ChinaDepartment of Oncology, The First Affiliated Hospital, Soochow University, Suzhou, ChinaHepatobiliary Center, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, Huai’an Second People’s Hospital, The Affiliated Huai’an Hospital, Xuzhou Medical University, Huai’an, ChinaDepartment of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Oncology, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Pathology, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaHepatobiliary Center, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, Nanjing Red Cross Hospital, Nanjing, ChinaHepatobiliary Center, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaHepatobiliary Center, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaHepatobiliary Center, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaHepatobiliary Center, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, Liyang People’s Hospital, Liyang, ChinaHepatobiliary Center, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaPurposeImmune checkpoint inhibitors plus antiangiogenic tyrosine kinase inhibitors may offer a first-line treatment for advanced hepatocellular carcinoma (HCC). In this phase 2 trial [registered with clinicaltrials.gov (NCT04052152)], we investigated the safety and efficacy of first-line anti-PD-1 antibody sintilimab plus antiangiogenic TKI anlotinib for advanced HCC.Methods and MaterialsPathologically-proven advanced HCC patients received sintilimab (200 mg) on day 1 and anlotinib (12 mg) once daily on days 1 to 14 every 3 weeks, with a safety run-in for the first six participants to assess dose-limiting toxicities (DLTs). The primary endpoints were safety and objective response rate (ORR) per RECIST v1.1.ResultsTwenty advanced HCC patients were enrolled. No DLTs occurred in the safety run-in. All patients had treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 8 (40.0%) patients, the most common being decreased platelet count (10.0%) and increased γ-glutamyl transferase (10.0%). No grade 4/5 TRAEs occurred. Five (25%) patients developed immune-related AEs. The ORR was 35.0% (95%CI 15.4%-59.2%) per RECIST v1.1 and 55.0% (95%CI 31.5%-76.9%) per modified RECIST. At data cutoff (March 31, 2021), the median progression-free survival was 12.2 months (95%CI, 3.8 to not reached). The median PFS was significantly longer in patients with lower LDH levels (not reached [NR], 95% CI, 8.7 to NR vs. higher LDH levels 5.2 months, 95% CI 3.4 to NR; P=0.020) and a CONUT score ≤2 (NR, 95% CI 5.1 to NR vs. CONUT score >2 6.2 months, 95% CI 1.8 to NR; P=0.020). Furthermore, patients showing tumor response had a significantly higher median proportion of CD16+CD56+ NK cells than patients who had stable or progressive disease (21.6% vs. 14.6%; P=0.026).ConclusionSintilimab plus anlotinib showed promising clinical activities with manageable toxicity as first-line treatment of advanced HCC.https://www.frontiersin.org/articles/10.3389/fonc.2022.909035/fulladvanced hepatocellular carcinomasintilimabanlotinibanti-PD1receptor tyrosine kinase |
| spellingShingle | Xiaofeng Chen Xiaofeng Chen Wei Li Xiaofeng Wu Fengjiao Zhao Deqiang Wang Hao Wu Yanhong Gu Xiao Li Xiaofeng Qian Jun Hu Changxian Li Yongxiang Xia Jianhua Rao Xinzheng Dai Qianwen Shao Jie Tang Xiangcheng Li Yongqian Shu Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study Frontiers in Oncology advanced hepatocellular carcinoma sintilimab anlotinib anti-PD1 receptor tyrosine kinase |
| title | Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study |
| title_full | Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study |
| title_fullStr | Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study |
| title_full_unstemmed | Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study |
| title_short | Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study |
| title_sort | safety and efficacy of sintilimab and anlotinib as first line treatment for advanced hepatocellular carcinoma keep g04 a single arm phase 2 study |
| topic | advanced hepatocellular carcinoma sintilimab anlotinib anti-PD1 receptor tyrosine kinase |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.909035/full |
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