 |
| FDA Approves ZEJULA (Niraparib) for the Maintenance Treatment of Adult Patients With Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer who are in a Complete or Partial Response to Platinum-Based Chemotherapy On March 27th, 2017, the U.S. Food and Drug Administration (FDA) approved ZEJULA (niraparib) for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. The approved recommended dosage of ZEJULA is 300 mg (three 100 mg capsules) taken orally once daily with or without food. ZEJULA treatment should be continued until disease progression or unacceptable toxicity. Patients should start treatment with ZEJULA no later than 8 weeks after their most recent platinum-containing regimen. Do not start ZEJULA until patients have recovered (≤ Grade 1) from hematological toxicity caused by previous chemotherapy. Test complete blood counts weekly for the first month, then monitor monthly for the next 11 months and periodically thereafter for clinically significant changes. Withhold or discontinue ZEJULA, as necessary, based upon parameters outlined in the prescribing information linked below. Monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with ZEJULA. Manage hypertension with antihypertensive medications as well as adjustment of the ZEJULA dose, if necessary. Mechanism of Action (MOA), General Pharmacokinetics (PK), and Pharmacodynamics (PD)
Use in Specific Populations Age (18 to 65 years old), race/ethnicity, mild hepatic impairment, and mild to moderate renal impairment had no clinically significant effect on the PK of niraparib. The PK and safety of niraparib in patients with severe renal impairment, end stage renal disease undergoing hemodialysis, or moderate to severe hepatic impairment are unknown. Efficacy and Safety ZEJULA was studied at the approved dosage in a double-blind, placebo-controlled trial in which patients (n=553) with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomized in a 2:1 ratio to ZEJULA or matched placebo within 8 weeks of the last therapy. Eligible patients were subsequently assigned to two cohorts based on the results of the BRACAnalysis CDx companion diagnostic test. Patients with (n=203) and without (n=350) deleterious or suspected germline BRCA mutations were assigned to the gBRCAmut and non-gBRCAmut cohort, respectively. The major efficacy outcome measure was progression-free survival (PFS). In the gBRCAmut cohort, an estimated median (95% CI) PFS of 21 months (12.9, Not Reached) was observed for patients treated with ZEJULA compared to 5.5 months (3.8, 7.2) for those on placebo (hazard ratio (HR) (95% CI): 0.26 (0.17, 0.41), p<0.0001). Similarly, in the non-gBRCAmut cohort, an estimated median (95% CI) PFS of 9.3 months (7.29, 11.2) was observed for patients treated with ZEJULA compared to 3.9 months (3.7, 5.5) for those on placebo (HR (95% CI): 0.45 (0.34, 0.61), p<0.0001). At the time of the efficacy analysis, limited overall survival data were available with 17% deaths reported across the two cohorts. Based on a safety analysis of 367 patients treated with ZEJULA, the most commonly observed adverse reactions (incidence ≥ 10%) were thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue/asthenia, decreased appetite, urinary tract infection, AST/ALT elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, and hypertension. Serious adverse reactions included myelodysplastic syndrome/acute myeloid leukemia, bone marrow suppression, and cardiovascular effects. Full prescribing information is available at https://go.usa.gov/xX5ve. Visit Drugs@FDA at http://go.usa.gov/cMsjT for prescribing and patient information, approval letters, reviews and other information for FDA-approved drug products, which are often available shortly following approval. A non-comprehensive list of examples of clinical substrates, inhibitors and inducers for metabolic and transporter system related interactions may be found at https://go.usa.gov/xXY9C. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA's MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178), or by mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088). We always welcome your thoughts regarding the format, content, and utility of the information you receive via this Burst email initiative. Comments may be sent via email to ocp@fda.hhs.gov. This Burst was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA. FDA/Center for Drug Evaluation and Research (CDER) |
| This email was sent to bsamad2007.adnan@blogger.com using GovDelivery, on behalf of: U.S. Food & Drug Administration (FDA) · 10903 New Hampshire Ave · Silver Spring, MD 20993 · 1-888-INFO-FDA (1-888-463-6332) |  |
Comments
Post a Comment