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强生宣布中国首个且目前唯一治疗BRCA突变转移性去势抵抗性前列腺癌的复方制剂泽倍珂®在华获批[1]
prnasia 2024-10-21

倍珂®是每日一次的口服复方制剂,用于联合泼尼松或泼尼松龙一线治疗携带BRCA1/2突变的转移性去势抵抗性前列腺癌成人患者,临床证实其相较标准治疗可显著延长影像学无进展生存期[2]。

北京2024年10月21日 /美通社/ --  强生公司今日宣布,旗下创新治疗药物泽倍珂®(尼拉帕利阿比特龙片)正式获得国家药品监督管理局批准。作为目前国内首个且唯一获批的双效复方制剂[1],泽倍珂®联合泼尼松或泼尼松龙用于治疗携带胚系和/或体系BRCA基因突变的转移性去势抵抗性前列腺癌成人患者(mCRPC)[3]。

泽倍珂®是BRCA1/2突变mCRPC成人患者的一线靶向治疗方案[4]。作为一种高选择性聚腺苷二磷酸核糖聚合酶(PARP)抑制剂[5],尼拉帕利和醋酸阿比特龙的组合联合泼尼松或泼尼松龙,能够靶向mCRPC患者的两种致癌驱动因素——雄激素受体轴和BRCA1/2突变[3],[6],[7]。经临床验证,泽倍珂®联合泼尼松或泼尼松龙可显著延长BRCA1/2突变mCRPC患者的影像学无进展生存期(rPFS)。此外,与安慰剂相比,尼拉帕利还显示出总体生存 (OS)改善的趋势,可显著延长至症状进展时间(TSP)和至细胞毒性化疗起始时间(TCC),同时并维持了患者的生活质量[8]。

近年来,中国前列腺癌的发病率显著上升。据国家癌症中心最新发布的2022年度中国恶性肿瘤疾病负担报告显示,我国前列腺癌的发病率为每10万人中18.61例,已成为男性泌尿生殖系统中最常见的肿瘤[9]。尽管随着我国医疗水平的提高,前列腺癌的治疗已经取得一定进展,但是mCRPC仍然是一种致命的疾病[10],[11]。据统计,大约10-15%的mCRPC患者携带BRCA1/2基因突变[12],[13],而携带BRCA1/2基因突变的前列腺癌往往恶性程度更高,可能具有更强的侵袭性和更高的转移性疾病比例,患者的生存结局更差[14],[15],[16],[17],[18]。因此,NCCN和EAU等国内外权威指南均推荐对mCRPC患者进行基因检测,以提供更加精准的治疗决策,改善患者临床获益[19],[20]。

强生创新制药中国区总裁Cherry Huang女士表示:"泽倍珂®的获批再次印证了前列腺癌精准治疗时代的到来,突显了基因检测在前列腺癌诊疗中的重要意义。长期以来,强生始终关注不同疾病阶段前列腺癌患者的切实需求,持续引入创新疗法及产品组合,从前列腺癌的晚期治疗,进一步覆盖到更早期阶段。同时,我们也希望让更多患者实现前列腺癌全程管理,在早期、规范化、足疗程的诊疗中获得更长生存。"

此次泽倍珂®的获批是基于一项随机、双盲、安慰剂对照的多中心III期MAGNITUDE研究。结果显示,在BRCA突变亚组中,尼拉帕利联合醋酸阿比特龙加泼尼松或泼尼松龙(AAP)显著降低影像学进展或死亡风险达47%(rPFS, HR=0.53;95%CI 0.36,0.79;p=0.0014)[3]。在第二次期中分析时,中位随访时间为24.8个月,与安慰剂联合AAP的10.9个月相比,尼拉帕利联合AAP治疗BRCA突变亚组的中位rPFS为19.5个月(HR,0.55[95%(CI),0.39-0.78])[21]。此外,尼拉帕利在至症状进展时间(TSP)上有统计学意义上的获益,与对照组相比,症状进展风险显著降低了46%(未达到中位数与23.6个月相比;HR=0.54,95% CI:0.35-0.85;P=0.0071)[3]。值得注意的是,试验还观察到,接受尼拉帕利联合APP治疗的BRCA1/2 基因突变 mCRPC 患者与接受安慰剂联合AAP治疗的患者相比,尼拉帕利在至细胞毒性化疗起始时间(TCC)上达到统计学意义和临床意义的改善(中位时间未达到 vs. 27.3 个月;HR:0.56,95% CI:0.35-0.90; p=0.0152)[3]。

在安全性方面,研究显示尼拉帕利和AAP联合用药与单药的已知安全性一致。该联合疗法最常见的不良反应(>10%)包括肌肉骨骼疼痛、疲乏、便秘、高血压、恶心、水肿、呼吸困难等[3]。

[1] 强生公司基于《化学药品注册分类及申报资料要求》中2类(2.3)改良型新药新复方制剂的类别递交申请并获得了审批。2类:境内外均未上市的改良型新药。指在已知活性成份的基础上,对其结构、剂型、处方工艺、给药途径、适应症等进行优化,且具有明显临床优势的药品。2.3含有已知活性成份的新复方制剂,且具有明显临床优势。

[2] Sumanasuriya S & De Bono J. Treatment of Advanced Prostate Cancer—A Review of Current Therapies and Future Promise. Cold Spring Harb Perspect Med. 2018;8(6): a030635.

[3] AKEEGA® China Prescribing Information, August 2024

[4] K. N. Chi et al. Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial. Ann Oncol 2023 Sep;34(9):772-782.

[5] European Medicines Agency. Zejula (niraparib) Summary of Product Characteristics. February 2023.

[6] Clinicaltrials.gov. A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration Sensitive Prostate Cancer (mCSPC) (AMPLITUDE). Available at: https://clinicaltrials.gov/ct2/show/NCT04497844. Last accessed: April 2023.

[7] Gsk.com. GSK completes acquisition of TESARO, an oncology focused biopharmaceutical company. Available at: https://www.gsk.com/en-gb/media/press-releases/gsk-completes-acquisition-of-tesaro-an-oncology-focused-biopharmaceutical-company/. Last accessed: April 2023.

[8] Merseburger AS, et al. Perspectives on treatment of metastatic castration-resistant prostate cancer. Oncologist. 2013;18(5):558-567.

[9] Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W, He J: Cancer incidence and mortality in China, 2022. Journal of the National Cancer Center 2024, 4(1):47-53.

[10] Sumanasuriya S & De Bono J. Treatment of Advanced Prostate Cancer—A Review of Current Therapies and Future Promise. Cold Spring Harb Perspect Med. 2018;8(6):a030635.

[11] Scott RJ, et al. Genetic testing for homologous recombination repair (HRR) in metastatic castration-resistant prostate cancer (mCRPC): challenges and solutions. Oncotarget. 2021;12(16):1600-1614.

[12] Abida W, et al. Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making. JCO Precis Oncol. 2017;2017:PO.17.00029.

[13] Shore N, et al. Systematic Literature Review of the Epidemiology of Advanced Prostate Cancer and Associated Homologous Recombination Repair Gene Alterations. The Journal of Urology. 2021;205(4):977–986.

[14] Scott RJ, Mehta A, Macedo GS, Borisov PS, Kanesvaran R, El Metnawy W. Genetic testing for homologous recombination repair (HRR) in metastatic castration-resistant prostate cancer (mCRPC): challenges and solutions. Oncotarget. 2021 Aug 3;12(16):1600-1614. doi: 10.18632/oncotarget.28015. PMID: 34381565; PMCID: PMC8351605.

[15] Castro E, Romero-Laorden N, Del Pozo A, et al. PROREPAIR-B: A prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37(6):490-503. doi:10.1200/JCO.18.00358.

[16] Cavanagh, H., & Rogers, K. M. (2015). The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers. Hereditary cancer in clinical practice, 13(1), 16. 

[17] Messina, C., Cattrini, C., Soldato, D., et al (2020). BRCA mutations in prostate cancer: Prognostic and predictive Implications. J Oncol., 2020, 4986365.

[18] Na, R., Zheng, S. L., Han, M., et al (2017). Germline mutations in ATM and BRCA1/2 distinguish risk for lethal and indolent prostate cancer and are associated with early age at death. European Urology, 71(5), 740–747.

[19] NCCN Clinical Practice Guideline in Prostate Cancer 2024 v4.

[20] EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer 2023.

[21] Eleni Efstathiou, et al. 2023ASCO GU abstract 170.

 

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