Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.
Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Center, Changsha, China.
Lancet Oncol. 2022 Oct;23(10):1249-1260. doi: 10.1016/S1470-2045(22)00507-1. Epub 2022 Sep 5.
Rezvilutamide, a novel androgen-receptor inhibitor with low blood-brain barrier penetration, has shown potent antitumour activity against metastatic castration-resistant prostate cancer. In this study, we aimed to evaluate the efficacy and safety of rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy (ADT) for high-volume, metastatic, hormone-sensitive prostate cancer.
CHART is a randomised, open-label, phase 3 study done at 72 hospitals in China, Poland, Czech Republic, and Bulgaria. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had high-volume metastatic, hormone-sensitive prostate cancer. Previous chemotherapy or other localised treatment for prostate cancer were not allowed. Patients were randomly assigned (1:1) to receive ADT plus either rezvilutamide (240 mg) or bicalutamide (50 mg) orally once daily. Randomisation was done via an interactive response technology system (block size of four) and stratified according to ECOG performance status and presence of visceral metastasis (excluding lymph nodes). Herein, we present the results of the preplanned interim analyses for the two co-primary endpoints of radiographic progression-free survival assessed by a blinded independent review committee and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study medication. This study is ongoing, but is closed to recruitment. This trial is registered with ClinicalTrials.gov, NCT03520478.
Between June 28, 2018, and Aug 6, 2020, 792 patients were screened and 654 patients were randomly assigned to receive rezvilutamide plus ADT (n=326) or bicalutamide plus ADT (n=328). At the preplanned interim analysis for radiographic progression-free survival (data cutoff May 16, 2021), the median follow-up duration was 21·2 months (IQR 16·6-25·8). Rezvilutamide significantly improved radiographic progression-free survival compared with bicalutamide (median radiographic progression-free survival not reached [95% CI not reached-not reached] vs 25·1 months [95% CI 15·7-not reached]; hazard ratio [HR] 0·44 [95% CI 0·33-0·58]; p<0·0001). At the preplanned interim analysis for overall survival (data cutoff Feb 28, 2022), the median follow-up duration was 29·3 months (IQR 21·0-33·3). Rezvilutamide significantly improved overall survival compared with bicalutamide (HR 0·58 [95% CI 0·44-0·77]; p=0·0001; median overall survival was not reached [95% CI not reached-not reached] vs not reached [36·2-not reached]). The most common grade 3 or worse adverse events of any cause in the safety population were hypertension (26 [8%] of 323 patients in the rezvilutamide group vs 24 [7%] of 324 patients in the bicalutamide group), hypertriglyceridaemia (24 [7%] vs seven [2%]), increased weight (20 [6%] vs 12 [4%]), anaemia (12 [4%] vs 16 [5%]), and hypokalaemia (11 [3%] vs four [1%]). Serious adverse events were reported in 90 (28%) of 323 patients in the rezvilutamide group and 69 (21%) of 324 patients in the bicalutamide group. No treatment-related deaths occurred in patients in the rezvilutamide group; one treatment-related death of unknown specific cause (<1%) occurred in the bicalutamide group.
In the two interim analyses, rezvilutamide plus ADT significantly improved radiographic progression-free survival and overall survival compared with bicalutamide plus ADT in patients with high-volume, metastatic, hormone-sensitive prostate cancer, with a tolerable safety profile.
Jiangsu Hengrui Pharmaceuticals.
雷扎卢胺是一种新型的雄激素受体抑制剂，其血脑屏障穿透率较低，已显示出对转移性去势抵抗性前列腺癌具有强大的抗肿瘤活性。在这项研究中，我们旨在评估雷扎卢胺与比卡鲁胺联合雄激素剥夺疗法（ADT）用于治疗大体积、转移性、激素敏感型前列腺癌的疗效和安全性。
CHART 是一项在中国、波兰、捷克共和国和保加利亚的 72 家医院进行的随机、开放标签、III 期研究。纳入标准为年龄 18 岁或以上，东部肿瘤协作组（ECOG）体能状态为 0 或 1，患有大体积转移性、激素敏感型前列腺癌。既往不允许接受化疗或其他局部前列腺癌治疗。患者被随机分配（1:1）接受 ADT 加雷扎卢胺（240mg）或比卡鲁胺（50mg）每日一次口服治疗。随机分组通过交互式反应技术系统（分组大小为 4）进行，并根据 ECOG 体能状态和是否存在内脏转移（不包括淋巴结）进行分层。在此，我们报告了预先计划的两个主要终点的中期分析结果，即盲法独立审查委员会评估的影像学无进展生存期和在意向治疗人群中的总生存期。所有接受至少一剂研究药物的患者均进行了安全性评估。该研究正在进行中，但已关闭入组。本试验在 ClinicalTrials.gov 注册，NCT03520478。
在 2018 年 6 月 28 日至 2020 年 8 月 6 日期间，有 792 名患者被筛选，654 名患者被随机分配接受雷扎卢胺加 ADT（n=326）或比卡鲁胺加 ADT（n=328）治疗。在影像学无进展生存期的预先计划的中期分析（数据截止日期 2021 年 5 月 16 日）中，中位随访时间为 21.2 个月（IQR 16.6-25.8）。与比卡鲁胺相比，雷扎卢胺显著改善了影像学无进展生存期（中位影像学无进展生存期未达到[95%CI 未达到-未达到]vs 25.1 个月[95%CI 15.7-未达到]；风险比[HR]0.44[95%CI 0.33-0.58]；p<0.0001）。在总生存期的预先计划的中期分析（数据截止日期 2022 年 2 月 28 日）中，中位随访时间为 29.3 个月（IQR 21.0-33.3）。与比卡鲁胺相比，雷扎卢胺显著改善了总生存期（HR 0.58[95%CI 0.44-0.77]；p=0.0001；中位总生存期未达到[95%CI 未达到-未达到]vs 未达到[36.2-未达到]）。安全性人群中最常见的任何原因的 3 级或更高级别的不良事件是高血压（雷扎卢胺组 323 例中有 26 例[8%]，比卡鲁胺组 324 例中有 24 例[7%]）、高甘油三酯血症（24 例[7%]vs 7 例[2%]）、体重增加（20 例[6%]vs 12 例[4%]）、贫血（12 例[4%]vs 16 例[5%]）和低钾血症（11 例[3%]vs 4 例[1%]）。雷扎卢胺组 323 例患者中有 90 例（28%）和比卡鲁胺组 324 例患者中有 69 例（21%）报告了严重不良事件。雷扎卢胺组无治疗相关死亡；比卡鲁胺组有 1 例（<1%）与治疗相关的死因不明的死亡事件。
在这两次中期分析中，与比卡鲁胺加 ADT 相比，雷扎卢胺加 ADT 显著改善了大体积、转移性、激素敏感型前列腺癌患者的影像学无进展生存期和总生存期，且安全性可接受。
江苏恒瑞医药。
