Shukui Qin, Yusheng Wang, Jun Yao, Yanyan Liu, Tienan Yi, Yueyin Pan, Zhendong Chen, Xizhi Zhang, Jin Lu, Junyan Yu, Yanjun Zhang, Peng Cheng, Yong Mao, Jian Zhang, Meiyu Fang, Yanming Zhang, Jing Lv, Runzi Li, Ning Dou, Qian Tang, Jun Ma
{"title":"治疗晚期实体瘤患者化疗所致血小板减少症的赫曲博帕：一项多中心、随机、双盲、安慰剂对照 II 期研究。","authors":"Shukui Qin, Yusheng Wang, Jun Yao, Yanyan Liu, Tienan Yi, Yueyin Pan, Zhendong Chen, Xizhi Zhang, Jin Lu, Junyan Yu, Yanjun Zhang, Peng Cheng, Yong Mao, Jian Zhang, Meiyu Fang, Yanming Zhang, Jing Lv, Runzi Li, Ning Dou, Qian Tang, Jun Ma","doi":"10.1177/17588359241260985","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy-induced thrombocytopenia (CIT) increases the risk of bleeding, necessitates chemotherapy dose reductions and delays, and negatively impacts prognosis.</p><p><strong>Objectives: </strong>This study aimed to evaluate the efficacy and safety of hetrombopag for the management of CIT in patients with advanced solid tumors.</p><p><strong>Design: </strong>A multicenter, randomized, double-blind, placebo-controlled, phase II study.</p><p><strong>Methods: </strong>Patients with advanced solid tumors who experienced a chemotherapy delay of ⩾7 days due to thrombocytopenia (platelet count <75 × 10<sup>9</sup>/L) were randomly assigned (1:1) to receive oral hetrombopag at an initial dose of 7.5 mg once daily or a matching placebo. The primary endpoint was the proportion of treatment responders, defined as patients resuming chemotherapy within 14 days (platelet count ⩾100 × 10<sup>9</sup>/L) and not requiring a chemotherapy dose reduction of ⩾15% or a delay of ⩾4 days or rescue therapy for two consecutive cycles.</p><p><strong>Results: </strong>Between 9 October 2021 and 5 May 2022, 60 patients were randomized, with 59 receiving ⩾1 dose of assigned treatment (hetrombopag/placebo arm, <i>n</i> = 28/31). The proportion of treatment responders was significantly higher in the hetrombopag arm than in the placebo arm [60.7% (17/28) <i>versus</i> 12.9% (4/31); difference of proportion: 47.6% (95% confidence interval (CI): 26.0-69.3); odds ratio = 10.44 (95% CI: 2.82-38.65); <i>p</i> value (nominal) based on the Cochran-Mantel-Haenszel: <0.001)]. During the double-blind treatment period, grade 3 or higher adverse events (AEs) occurred in 35.7% (10/28) of patients with hetrombopag and 38.7% (12/31) of patients on placebo. The most common grade 3 or higher AEs were decreased neutrophil count [35.7% (10/28) <i>versus</i> 35.5% (11/31)] and decreased white blood cell count [17.9% (5/28) <i>versus</i> 19.4% (6/31)]. Serious AEs were reported in 3.6% (1/28) of patients with hetrombopag and 9.7% (3/31) of patients with placebo.</p><p><strong>Conclusion: </strong>Hetrombopag is an effective and well-tolerated alternative for managing CIT in patients with solid tumors.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03976882.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241260985"},"PeriodicalIF":4.3000,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179448/pdf/","citationCount":"0","resultStr":"{\"title\":\"Hetrombopag for the management of chemotherapy-induced thrombocytopenia in patients with advanced solid tumors: a multicenter, randomized, double-blind, placebo-controlled, phase II study.\",\"authors\":\"Shukui Qin, Yusheng Wang, Jun Yao, Yanyan Liu, Tienan Yi, Yueyin Pan, Zhendong Chen, Xizhi Zhang, Jin Lu, Junyan Yu, Yanjun Zhang, Peng Cheng, Yong Mao, Jian Zhang, Meiyu Fang, Yanming Zhang, Jing Lv, Runzi Li, Ning Dou, Qian Tang, Jun Ma\",\"doi\":\"10.1177/17588359241260985\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Chemotherapy-induced thrombocytopenia (CIT) increases the risk of bleeding, necessitates chemotherapy dose reductions and delays, and negatively impacts prognosis.</p><p><strong>Objectives: </strong>This study aimed to evaluate the efficacy and safety of hetrombopag for the management of CIT in patients with advanced solid tumors.</p><p><strong>Design: </strong>A multicenter, randomized, double-blind, placebo-controlled, phase II study.</p><p><strong>Methods: </strong>Patients with advanced solid tumors who experienced a chemotherapy delay of ⩾7 days due to thrombocytopenia (platelet count <75 × 10<sup>9</sup>/L) were randomly assigned (1:1) to receive oral hetrombopag at an initial dose of 7.5 mg once daily or a matching placebo. The primary endpoint was the proportion of treatment responders, defined as patients resuming chemotherapy within 14 days (platelet count ⩾100 × 10<sup>9</sup>/L) and not requiring a chemotherapy dose reduction of ⩾15% or a delay of ⩾4 days or rescue therapy for two consecutive cycles.</p><p><strong>Results: </strong>Between 9 October 2021 and 5 May 2022, 60 patients were randomized, with 59 receiving ⩾1 dose of assigned treatment (hetrombopag/placebo arm, <i>n</i> = 28/31). The proportion of treatment responders was significantly higher in the hetrombopag arm than in the placebo arm [60.7% (17/28) <i>versus</i> 12.9% (4/31); difference of proportion: 47.6% (95% confidence interval (CI): 26.0-69.3); odds ratio = 10.44 (95% CI: 2.82-38.65); <i>p</i> value (nominal) based on the Cochran-Mantel-Haenszel: <0.001)]. During the double-blind treatment period, grade 3 or higher adverse events (AEs) occurred in 35.7% (10/28) of patients with hetrombopag and 38.7% (12/31) of patients on placebo. The most common grade 3 or higher AEs were decreased neutrophil count [35.7% (10/28) <i>versus</i> 35.5% (11/31)] and decreased white blood cell count [17.9% (5/28) <i>versus</i> 19.4% (6/31)]. Serious AEs were reported in 3.6% (1/28) of patients with hetrombopag and 9.7% (3/31) of patients with placebo.</p><p><strong>Conclusion: </strong>Hetrombopag is an effective and well-tolerated alternative for managing CIT in patients with solid tumors.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03976882.</p>\",\"PeriodicalId\":23053,\"journal\":{\"name\":\"Therapeutic Advances in Medical Oncology\",\"volume\":\"16 \",\"pages\":\"17588359241260985\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-06-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179448/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Medical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17588359241260985\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17588359241260985","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Hetrombopag for the management of chemotherapy-induced thrombocytopenia in patients with advanced solid tumors: a multicenter, randomized, double-blind, placebo-controlled, phase II study.
Background: Chemotherapy-induced thrombocytopenia (CIT) increases the risk of bleeding, necessitates chemotherapy dose reductions and delays, and negatively impacts prognosis.
Objectives: This study aimed to evaluate the efficacy and safety of hetrombopag for the management of CIT in patients with advanced solid tumors.
Design: A multicenter, randomized, double-blind, placebo-controlled, phase II study.
Methods: Patients with advanced solid tumors who experienced a chemotherapy delay of ⩾7 days due to thrombocytopenia (platelet count <75 × 109/L) were randomly assigned (1:1) to receive oral hetrombopag at an initial dose of 7.5 mg once daily or a matching placebo. The primary endpoint was the proportion of treatment responders, defined as patients resuming chemotherapy within 14 days (platelet count ⩾100 × 109/L) and not requiring a chemotherapy dose reduction of ⩾15% or a delay of ⩾4 days or rescue therapy for two consecutive cycles.
Results: Between 9 October 2021 and 5 May 2022, 60 patients were randomized, with 59 receiving ⩾1 dose of assigned treatment (hetrombopag/placebo arm, n = 28/31). The proportion of treatment responders was significantly higher in the hetrombopag arm than in the placebo arm [60.7% (17/28) versus 12.9% (4/31); difference of proportion: 47.6% (95% confidence interval (CI): 26.0-69.3); odds ratio = 10.44 (95% CI: 2.82-38.65); p value (nominal) based on the Cochran-Mantel-Haenszel: <0.001)]. During the double-blind treatment period, grade 3 or higher adverse events (AEs) occurred in 35.7% (10/28) of patients with hetrombopag and 38.7% (12/31) of patients on placebo. The most common grade 3 or higher AEs were decreased neutrophil count [35.7% (10/28) versus 35.5% (11/31)] and decreased white blood cell count [17.9% (5/28) versus 19.4% (6/31)]. Serious AEs were reported in 3.6% (1/28) of patients with hetrombopag and 9.7% (3/31) of patients with placebo.
Conclusion: Hetrombopag is an effective and well-tolerated alternative for managing CIT in patients with solid tumors.
期刊介绍：
Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
