Background 背景
Chemotherapy-induced anemia (CIA) is a common complication of cancer and an important risk factor leading to poor prognosis for patients. Recombinant human erythropoietin-α (rHuEPO-α) is standard of care for CIA; however, safety concerns remain. Roxadustat is the first hypoxia-inducible factor prolyl hydroxylase inhibitor approved for treatment of anemia in chronic kidney disease. This study evaluated the efficacy and safety of roxadustat for anemia in patients with non-myeloid malignancies receiving multi-cycle treatments of myelosuppressive chemotherapy.
化疗诱导的贫血(CIA)是癌症的常见并发症,也是导致患者预后不佳的重要风险因素。重组人重组人红细胞生成素-α(rHuEPO-α)是 CIA 的标准治疗方法;然而,安全性仍然存在疑虑。罗沙度司他是首个获批用于治疗慢性肾脏疾病贫血的缺氧诱导因子脯氨酸羟化酶抑制剂。本研究评估了罗沙度司他对非髓系恶性肿瘤患者贫血的疗效和安全性,这些患者接受多周期骨髓抑制化疗治疗。
化疗诱导的贫血(CIA)是癌症的常见并发症,也是导致患者预后不佳的重要风险因素。重组人重组人红细胞生成素-α(rHuEPO-α)是 CIA 的标准治疗方法;然而,安全性仍然存在疑虑。罗沙度司他是首个获批用于治疗慢性肾脏疾病贫血的缺氧诱导因子脯氨酸羟化酶抑制剂。本研究评估了罗沙度司他对非髓系恶性肿瘤患者贫血的疗效和安全性,这些患者接受多周期骨髓抑制化疗治疗。
Methods 方法
In this open-label, non-inferiority, multicenter Phase III study conducted in China, patients were randomized (1:1) to receive oral roxadustat or subcutaneous rHuEPO-α three times weekly (TIW) for 12 weeks. Roxadustat starting dosage was 100 mg, 120 mg, and 150 mg TIW (patients weighing 40‒<50, 50–60, and >60 kg). rHuEPO-α starting dosage was 150 IU/kg TIW. Both roxadustat and rHuEPO-α dosages could be modified to achieve hemoglobin (Hb) concentrations of 100–120 g/L. Primary efficacy endpoint was least-squares mean (LSM) change in Hb concentration from baseline to the concentration averaged over Weeks 9‒13. Adverse events (AEs) were monitored.
在中国进行的这项开放标签、非劣效性、多中心第三期研究中,患者被随机分配(1:1)接受口服罗沙司他或皮下注射重组人促红细胞生成素α(rHuEPO-α)每周三次(TIW)治疗 12 周。罗沙司他的起始剂量为 100 毫克、120 毫克和 150 毫克 TIW(患者体重为 40‒<50、50–60 和>60 千克)。rHuEPO-α的起始剂量为每周 150 国际单位/千克。罗沙司他和 rHuEPO-α的剂量可以调整以达到血红蛋白(Hb)浓度为 100–120 克/升。主要疗效终点是基线至第 9‒13 周平均浓度的血红蛋白浓度的最小二乘均值(LSM)变化。监测不良事件(AEs)。
在中国进行的这项开放标签、非劣效性、多中心第三期研究中,患者被随机分配(1:1)接受口服罗沙司他或皮下注射重组人促红细胞生成素α(rHuEPO-α)每周三次(TIW)治疗 12 周。罗沙司他的起始剂量为 100 毫克、120 毫克和 150 毫克 TIW(患者体重为 40‒<50、50–60 和>60 千克)。rHuEPO-α的起始剂量为每周 150 国际单位/千克。罗沙司他和 rHuEPO-α的剂量可以调整以达到血红蛋白(Hb)浓度为 100–120 克/升。主要疗效终点是基线至第 9‒13 周平均浓度的血红蛋白浓度的最小二乘均值(LSM)变化。监测不良事件(AEs)。
Results 结果
Of 159 patients randomized (n=82, roxadustat; n=77, rHuEPO-α), 140 were included in the per protocol set (n=78, roxadustat; n=62, rHuEPO-α). The LSM (95% 2-sided confidence interval [CI]) change from baseline to Weeks 9‒13 in Hb concentration was 17.1 (13.58, 20.71) g/L with roxadustat and 15.4 (11.34, 19.50) g/L with rHuEPO-α. The lower bound of the 1-sided 97.5% CI for the treatment difference (‒3.4 g/L) was greater than the predefined non-inferiority margin of ‒6.6 g/L, establishing non-inferiority. Results were supported by key secondary endpoints. AE rates were generally comparable between treatments and consistent with previous findings, supporting a positive benefit-risk profile.
在随机分配的 159 名患者中(n=82,罗沙司他;n=77,rHuEPO-α),共有 140 名患者被纳入符合方案集(n=78,罗沙司他;n=62,rHuEPO-α)。LSM(95%双侧置信区间[CI])基线至第 9-13 周 Hb 浓度变化为罗沙司他 17.1(13.58,20.71)g/L,rHuEPO-α为 15.4(11.34,19.50)g/L。治疗差异(-3.4 g/L)的单侧 97.5% CI 的下限大于预定义的-6.6 g/L 的非劣效边界,证实了非劣效性。结果得到关键次要终点的支持。不良事件发生率在治疗间基本可比,并与先前的发现一致,支持积极的利弊风险概况。
在随机分配的 159 名患者中(n=82,罗沙司他;n=77,rHuEPO-α),共有 140 名患者被纳入符合方案集(n=78,罗沙司他;n=62,rHuEPO-α)。LSM(95%双侧置信区间[CI])基线至第 9-13 周 Hb 浓度变化为罗沙司他 17.1(13.58,20.71)g/L,rHuEPO-α为 15.4(11.34,19.50)g/L。治疗差异(-3.4 g/L)的单侧 97.5% CI 的下限大于预定义的-6.6 g/L 的非劣效边界,证实了非劣效性。结果得到关键次要终点的支持。不良事件发生率在治疗间基本可比,并与先前的发现一致,支持积极的利弊风险概况。
Conclusions 结论
Oral roxadustat was non-inferior to subcutaneous rHuEPO-α for anemia in patients with non-myeloid malignancies receiving multi-cycle treatments of myelosuppressive chemotherapy.
口服罗沙司他对接受多周期骨髓抑制化疗治疗的非髓样恶性肿瘤患者贫血的非劣效性不逊于皮下重组人促红细胞生成素α。
口服罗沙司他对接受多周期骨髓抑制化疗治疗的非髓样恶性肿瘤患者贫血的非劣效性不逊于皮下重组人促红细胞生成素α。
Clinical trial identification
临床试验识别
FGCL-4592-898. FGCL-4592-898。
Editorial acknowledgement
编辑致谢
Marjet Heitzer, PhD, Kay Square Scientific, Newtown. Square, PA
马杰特·海泽(Marjet Heitzer),博士,凯广场科学(Kay Square Scientific),纽敦广场,宾夕法尼亚州。
马杰特·海泽(Marjet Heitzer),博士,凯广场科学(Kay Square Scientific),纽敦广场,宾夕法尼亚州。
Legal entity responsible for the study
研究的法定实体
FibroGen, Inc. 斐博基因公司
Funding 资金
FibroGen, Inc. 斐博基因公司
Disclosure 披露
S. Lu: Financial Interests, Speaker, Consultant, Advisor, speaker fees, advisor/consultant: AstraZeneca; Financial Interests, Speaker, Consultant, Advisor, speaker fees: Hansoh, Hengrui Therapeutics; Financial Interests, Speaker, Consultant, Advisor, advisor/consultant: Pfizer, Boehringer Ingelheim, Hutchison, ZaiLab, GenomiCare, Yuhan Corporation, Menarini, InventisBio Co., Simcere Zaiming, Roche; Financial Interests, Research Funding, research support: AstraZeneca, Hutchison, BMS, Heng Rui, BeiGene, Roche, Hansoh, Lilly Suzhou, Fibrogen. J. Wu: Financial Interests, Advisory Role: AstraZeneca, Roche, Novartis, Heng Rui, Lilly, FibroGen; Financial Interests, Other, consultant: AstraZeneca, Roche, Novartis, Heng Rui, Lilly, FibroGen. J. Jiang: Financial Interests, Research Funding: Heng Rui, Roche, Alphamab Oncology, FibroGen. Q. Guo: Financial Interests, Advisory Role: AstraZeneca, Roche, Novartis, Heng Rui, Lilly, FibroGen; Financial Interests, Other, consultant: AstraZeneca, Roche, Novartis, Heng Rui, Lilly, FibroGen. Y. Liu: Financial Interests, Speaker, Consultant, Advisor: Xinda, BeiGene, Roche, Hengrui Therapeutics, AstraZeneca, Qilu, BMS, Roche; Financial Interests, Research Funding: AstraZeneca, BeiGene, Roche, FibroGen. H. Zhang: Financial Interests, Advisory Role: AstraZeneca, Roche, Pfizer, Heng Rui, BMS, BeiGene, Roche, Innovent; Financial Interests, Other, consultant: AstraZeneca, Pfizer, Heng Rui, BMS, BeiGene, Roche, Innovent; Financial Interests, Officer, consultant: Roche. L. Qian: Financial Interests, Research Funding: GSK Plc, Sanofi, Mundi Pharma, Hutchison Whampoa Limited (HWL), Dalian Wanchun Biotechnology Co., Ltd., Shanghai Lunsheng Pharmaceutical Technology Co., Ltd., Innovent (Suzhou), FibroGen. X. Dai: Financial Interests, Research Funding: Luye Pharma, FibroGen. Y. Xie: Financial Interests, Other, speaker fees: AstraZeneca, Roche, Heng Rui, Lilly, Pfizer, MSD, Simcere, FibroGen. T. Fu: Financial Interests, Advisory Role: Heng Rui, Ji Shi, FibroGen; Financial Interests, Other, consultant: Heng Rui, Ji Shi, FibroGen. T. Lee, Y. Lu, R. Ma, M. Eisner: Financial Interests, Full or part-time Employment: FibroGen; Financial Interests, Stocks or ownership: FibroGen.. All other authors have declared no conflicts of interest.
卢 S:财务利益,演讲者,顾问,顾问,演讲费用,顾问/顾问:阿斯利康;财务利益,演讲者,顾问,顾问,演讲费用:汉森,恒瑞治疗;财务利益,演讲者,顾问,顾问,顾问/顾问:辉瑞,勃林格殷格翰,和记,ZaiLab,基因美康,裕晏公司,美纳林,英飞拓生物有限公司,先声再明,罗氏;财务利益,研究资助,研究支持:阿斯利康,和记,BMS,恒瑞,北极星,罗氏,汉森,莱利苏州,费博基因。吴 J:财务利益,咨询角色:阿斯利康,罗氏,诺华,恒瑞,莱利,费博基因;财务利益,其他,顾问:阿斯利康,罗氏,诺华,恒瑞,莱利,费博基因。江 J:财务利益,研究资助:恒瑞,罗氏,阿法马肿瘤,费博基因。郭 Q:财务利益,咨询角色:阿斯利康,罗氏,诺华,恒瑞,莱利,费博基因;财务利益,其他,顾问:阿斯利康,罗氏,诺华,恒瑞,莱利,费博基因。Y. 刘:财务利益,发言人,顾问,顾问:新达,北基因,罗氏,恒瑞医药,阿斯利康,齐鲁,百时美施贵宝,罗氏;财务利益,研究资助:阿斯利康,北基因,罗氏,菲柏根。张:财务利益,咨询角色:阿斯利康,罗氏,辉瑞,恒瑞,百时美施贵宝,罗氏,信达;财务利益,其他,顾问:阿斯利康,辉瑞,恒瑞,百时美施贵宝,罗氏,信达;财务利益,官员,顾问:罗氏。钱:财务利益,研究资助:葛兰素史克股份有限公司,赛诺菲,明迪制药,和记黄埔有限公司,大连万春生物科技有限公司,上海伦生制药技术有限公司,信达(苏州),菲柏根。戴:财务利益,研究资助:庐业制药,菲柏根。谢:财务利益,其他,演讲费:阿斯利康,罗氏,恒瑞,礼来,辉瑞,默沙东,先声,菲柏根。付:财务利益,咨询角色:恒瑞,吉士,菲柏根;财务利益,其他,顾问:恒瑞,吉士,菲柏根。李,陆,马,艾斯纳:财务利益,全职或兼职雇佣:菲柏根;财务利益,股票或所有权:菲柏根。 所有其他作者均声明没有利益冲突。
卢 S:财务利益,演讲者,顾问,顾问,演讲费用,顾问/顾问:阿斯利康;财务利益,演讲者,顾问,顾问,演讲费用:汉森,恒瑞治疗;财务利益,演讲者,顾问,顾问,顾问/顾问:辉瑞,勃林格殷格翰,和记,ZaiLab,基因美康,裕晏公司,美纳林,英飞拓生物有限公司,先声再明,罗氏;财务利益,研究资助,研究支持:阿斯利康,和记,BMS,恒瑞,北极星,罗氏,汉森,莱利苏州,费博基因。吴 J:财务利益,咨询角色:阿斯利康,罗氏,诺华,恒瑞,莱利,费博基因;财务利益,其他,顾问:阿斯利康,罗氏,诺华,恒瑞,莱利,费博基因。江 J:财务利益,研究资助:恒瑞,罗氏,阿法马肿瘤,费博基因。郭 Q:财务利益,咨询角色:阿斯利康,罗氏,诺华,恒瑞,莱利,费博基因;财务利益,其他,顾问:阿斯利康,罗氏,诺华,恒瑞,莱利,费博基因。Y. 刘:财务利益,发言人,顾问,顾问:新达,北基因,罗氏,恒瑞医药,阿斯利康,齐鲁,百时美施贵宝,罗氏;财务利益,研究资助:阿斯利康,北基因,罗氏,菲柏根。张:财务利益,咨询角色:阿斯利康,罗氏,辉瑞,恒瑞,百时美施贵宝,罗氏,信达;财务利益,其他,顾问:阿斯利康,辉瑞,恒瑞,百时美施贵宝,罗氏,信达;财务利益,官员,顾问:罗氏。钱:财务利益,研究资助:葛兰素史克股份有限公司,赛诺菲,明迪制药,和记黄埔有限公司,大连万春生物科技有限公司,上海伦生制药技术有限公司,信达(苏州),菲柏根。戴:财务利益,研究资助:庐业制药,菲柏根。谢:财务利益,其他,演讲费:阿斯利康,罗氏,恒瑞,礼来,辉瑞,默沙东,先声,菲柏根。付:财务利益,咨询角色:恒瑞,吉士,菲柏根;财务利益,其他,顾问:恒瑞,吉士,菲柏根。李,陆,马,艾斯纳:财务利益,全职或兼职雇佣:菲柏根;财务利益,股票或所有权:菲柏根。 所有其他作者均声明没有利益冲突。
Article info 文章信息
Identification 识别
DOI: https://doi.org/10.1016/j.annonc.2023.10.099
DOI:https://doi.org/10.1016/j.annonc.2023.10.099
Copyright 版权
© 2023 European Society for Medical Oncology. Published by Elsevier Inc. All rights reserved.
© 2023 年欧洲医学肿瘤学会。由爱思唯尔公司出版。保留所有权利。
© 2023 年欧洲医学肿瘤学会。由爱思唯尔公司出版。保留所有权利。
ScienceDirect 科学直达
Access this article on ScienceDirect在 ScienceDirect 上访问这篇文章
Related Articles 相关文章
- Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial
在手术切除的 II-IIIA 期非小细胞肺癌(IMpower010)中化疗后辅助使用阿特珠单抗的总生存率:一项随机、多中心、开放标签、III 期试验Annals of OncologyJuly 17, 2023
《肿瘤学年鉴》2023 年 7 月 17 日- Preview 预览IMpower010 (NCT02486718) demonstrated significantly improved disease-free survival (DFS) with adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in the programmed death-ligand 1 (PD-L1)-positive and all stage II-IIIA non-small-cell lung cancer (NSCLC) populations, at the DFS interim analysis. Results of the first interim analysis of overall survival (OS) are reported here.
- Full-Text 全文
- Preview 预览
- Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial
Pembrolizumab 单药治疗与化疗在铂类预处理、复发性或转移性鼻咽癌(KEYNOTE-122)中的比较:一项开放标签、随机、III 期试验Annals of OncologyDecember 16, 2022
《肿瘤学年鉴》2022 年 12 月 16 日- Preview 预览Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented.
- Full-Text 全文
- Preview 预览
- 936P Triple oral metronomic chemotherapy (OMCT) versus physician choice chemotherapy after failure of platinum-based therapy in advanced head and neck squamous cell cancer (HNSCC): A phase III randomized open-label study
936P 三重口服节律化化疗(OMCT)与铂类化疗失败后晚期头颈鳞状细胞癌(HNSCC)患者的医生选择化疗:一项 III 期随机开放标签研究Annals of Oncology 肿瘤学年鉴- Preview 预览Advanced HNSCC patients with platinum-refractory disease have limited treatment options and poor outcomes, especially in resource-constrained settings. Triple metronomic therapy, a low-dose continuous chemotherapeutic strategy, has shown promise in phase 2 trials but requires further validation. We aimed to evaluate triple OMCT's efficacy in improving overall survival (OS) compared to physician-choice chemotherapy (PCC).
- Full-Text 全文
- Preview 预览
- TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes
TROPHY-U-01,一项Ⅱ期开放标签研究,评估在经过铂类化疗和检查点抑制剂治疗后进展的转移性膀胱癌患者中使用 sacituzumab govitecan 的安全性和疗效结果更新Annals of OncologyJanuary 18, 2024
《肿瘤学年鉴》2024 年 1 月 18 日- Preview 预览Sacituzumab govitecan (SG) is a Trop-2-directed antibody–drug conjugate containing cytotoxic SN-38, the active metabolite of irinotecan. SG received accelerated US Food and Drug Administration approval for locally advanced (LA) or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy and a checkpoint inhibitor, based on cohort 1 of the TROPHY-U-01 study. Mutations in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene are associated with increased adverse events (AEs) with irinotecan-based therapies.
- Full-Text 全文
- Preview 预览
- 288MO InnovaTV 301/ENGOT-cx12/GOG-3057: A global, randomized, open-label, phase III study of tisotumab vedotin vs investigator’s choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer
288MO InnovaTV 301/ENGOT-cx12/GOG-3057:一项全球性、随机、开放标签、Ⅲ期研究,比较 Tisotumab Vedotin 与研究者选择的化疗在 2L 或 3L 复发性或转移性宫颈癌中的疗效Annals of Oncology 肿瘤学年鉴- Preview 预览Tisotumab vedotin (TV) is an investigational antibody-drug conjugate composed of a tissue factor-directed human monoclonal antibody covalently linked to cytotoxic MMAE. In the US, TV monotherapy received accelerated approval for the treatment of adult pts with recurrent or metastatic cervical cancer (r/mCC) with disease progression on or after chemotherapy. Here, innovaTV 301 (NCT04697628) study results of TV vs investigator’s choice of chemotherapy in pts with r/mCC following 1L therapy are presented.
- Full-Text 全文
- Preview 预览