FDA的药物评估和研究中心血液和肿瘤学产品办公室主任Richard Pazdur博士说：“维持治疗是对初次治疗积极响应的患者的癌症治疗方案的重要组成部分， FDA肿瘤学卓越中心主任。“Zejula为患者提供了一种新的治疗方案，可能有助于延缓这些癌症的未来发展，无论它们是否具有特定的基因突变。”
● 推荐剂量是300 mg每天1次有或无食物服用.
可得到ZEJULA为胶囊有一个白色体部用黑墨水印有“100 mg”，和一个紫色帽用白色水印有“Niraparib”。每粒胶囊含100 mg的niraparib游离碱。
Zejula (niraparib capsules)
Zejula (niraparib) is a poly(ADP-ribose) polymerase (PARP) inhibitor.
Zejula is specifically indicated for the maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.
Zejula is supplied as a capsule for oral administration. The recommended dose of Zejua as monotherapy is 300 mg (three 100 mg capsules) taken orally once daily. Zejula should be administered at approximately the same time each day. Each capsule should be swallowed whole and may be taken with or without food.
Patients should start treatment with Zejula no later than 8 weeks after their most recent platinum-containing regimen.
Zejula treatment should be continued until disease progression or unacceptable toxicity. In the case of a missed dose, the next dose should be administered at its regularly scheduled time. If a patient vomits or misses a dose of Zejula, an additional dose should not be taken.
Please see drug label for additional modifications.
The FDA approval of Zejula was based on NOVA, a double-blind, placebo-controlled trial in which 553 patients with platinum sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomized 2:1 to Zejula 300 mg orally daily or matched placebo within 8 weeks of the last therapy.
All patients had received at least two prior platinum-containing regimens and were in response (complete or partial) to their most recent platinum-based regimen. The major efficacy outcome measure, PFS (progression-free survival), was determined primarily by central independent assessment per RECIST. Among patients who were germline BRCA mutation carriers, the niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS.
The median PFS for patients treated with niraparib was 21.0 months, compared to 5.5 months for control (p < 0.0001). For patients who were not germline BRCA mutation carriers but whose tumors were determined to be HRD positive, the niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS. The median PFS for patients with HRD-positive tumors who were treated with niraparib was 12.9 months, compared to 3.8 months for control (p < 0.0001).
Niraparib also showed statistical significance in the overall non-germline BRCA mutant cohort, which included patients with both HRD-positive and HRD-negative tumors. The niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS. The median PFS for patients treated with niraparib was 9.3 months, compared to 3.9 months for control (p < 0.0001).
Mechanism of Action
Zejula (niraparib) is an inhibitor of poly(ADP-ribose) polymerase (PARP) enzymes, PARP-1 and PARP-2, which play a role in DNA repair. In vitro studies have shown that niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis and cell death.
Increased niraparib-induced cytotoxicity was observed in tumor cell lines with or without deficiencies in BRCA1/2.
Niraparib decreased tumor growth in mouse xenograft models of human cancer cell lines with deficiencies in BRCA1/2 and in human patient-derived xenograft tumor models with homologous recombination deficiency that had either mutated or wild type BRCA1/2.
Zejula will be available as 100mg strength capsules in 90-count bottles.