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RUBRACA(rucaparib)tablets
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第一个也是唯一的PARP抑制剂：RUBRACA（Rucaparib）获美国FDA批准用于治疗晚期卵巢癌
FDA加速批准RUBRACA™（rucaparib）用于治疗晚期卵巢癌的妇女与临床种系或体细胞BRCA突变的单一治疗
•美国第一个也是唯一的PARP抑制剂表示治疗已经用两种或更多种化疗治疗的晚期卵巢癌患者，并且具有有害的种系或体细胞BRCA突变
•Rubraca基于客观反应率和反应持续时间，根据FDA的加速审批计划获得批准
•最常见的3-4级不良反应是贫血; 最常见的3-4级实验室异常为血红蛋白减少
近日,美国食品和药物管理局FDA批准Rubraca TM（rucaparib）片剂作为单一疗法用于治疗已经用两种或更多种化学疗法治疗的有害BRCA突变（种系和/或体细胞）相关晚期卵巢癌的患者，基于FDA批准的用于Rubraca的伴随诊断选择用于治疗。
批准日期：2016年12月19日 公司：Clovis Oncology, Inc.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use RUBRACA safely and effectively. See full prescribing information for RUBRACA.
RUBRACA™ (rucaparib) tablets, for oral use
Initial U.S. Approval: 2016
INDICATIONS AND USAGE
RUBRACA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. Select patients for therapy based on an FDA-approved companion diagnostic for RUBRACA. (1, 2.1)
This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. (1, 14)
DOSAGE AND ADMINISTRATION
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Recommended dose is 600 mg orally twice daily with or without food. (2.2)
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Continue treatment until disease progression or unacceptable toxicity. (2.2)
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For adverse reactions, consider interruption of treatment or dose reduction. (2.3)
DOSAGE FORMS AND STRENGTHS
Tablets: 200 mg and 300 mg (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
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Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): MDS/AML occurred in patients exposed to RUBRACA, including one fatal event of AML. Monitor patients for hematological toxicity at baseline and monthly thereafter. Discontinue if MDS/AML is confirmed. (5.1)
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Embryo-Fetal Toxicity: RUBRACA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. (5.2, 8.1, 8.3)
ADVERSE REACTIONS
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Most common adverse reactions (≥ 20%) were nausea, fatigue (including asthenia), vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea. (6.1)
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Most common laboratory abnormalities (≥ 35%) were increase in creatinine, increase in ALT, increase in AST, decrease in hemoglobin, decrease in lymphocytes, increase in cholesterol, decrease in platelets, and decrease in absolute neutrophil count. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Clovis Oncology, Inc. at 1-844-258-7662 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
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Lactation: Advise women not to breastfeed. (8.2)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 12/2016
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
Rubraca™ is indicated as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca [see Dosage and Administration (2.1)].
This indication is approved under accelerated approval based on objective response rate and duration of response [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
2 DOSAGE AND ADMINISTRATION
2.1 Patient Selection
Select patients for the treatment of advanced ovarian cancer with Rubraca based on the presence of a deleterious BRCA mutation (germline and/or somatic)[see Indications and Usage (1) and Clinical Studies (14)]. Information on the FDA-approved test for the detection of a tumor BRCA mutation in patients with ovarian cancer is available at: http://www.fda.gov/CompanionDiagnostics.
2.2 Recommended Dose
The recommended dose of Rubraca is 600 mg (two 300 mg tablets) taken orally twice daily with or without food.
Continue treatment until disease progression or unacceptable toxicity.
If a patient misses a dose of Rubraca, instruct the patient to take the next dose at its scheduled time. Vomited doses should not be replaced.
2.3 Dose Modifications for Adverse Reactions
To manage adverse reactions, consider interruption of treatment or dose reduction. Recommended dose reductions are indicated in Table 1.
3 DOSAGE FORMS AND STRENGTHS
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Tablets (200 mg): blue, round, immediate-release, film-coated, debossed with “C2”.
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Tablets (300 mg): yellow, oval, immediate-release, film-coated, debossed with “C3”.
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Myelodysplastic Syndrome/Acute Myeloid Leukemia
Myelodysplastic syndrome (MDS)/Acute Myeloid Leukemia (AML) was reported in 2 of 377 (0.5%) patients with ovarian cancer treated with Rubraca. The duration of Rubraca treatment prior to the diagnosis of MDS/AML was 57 days and 539 days. Both patients received prior treatment with platinum and other DNA damaging agents.
In addition, AML was reported in 2 (< 1%) patients with ovarian cancer enrolled in a blinded, randomized trial eva luating Rubraca versus placebo. One case of AML was fatal. The duration of treatment prior to the diagnosis of AML was 107 days and 427 days. Both patients had received prior treatment with platinum and other DNA damaging agents.
Monitor complete blood count testing at baseline and monthly thereafter. Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). For prolonged hematological toxicities, interrupt Rubraca and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.
5.2 Embryo-Fetal Toxicity
Rubraca can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings from animal studies. In an animal reproduction study, administration of rucaparib to pregnant rats during organogenesis resulted in embryo-fetal death at maternal exposure that were 0.04 times the AUC in patients receiving the recommended dose of 600 mg twice daily. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].
6 ADVERSE REACTIONS
The following serious adverse reactions are discussed elsewhere in the labeling:
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Myelodysplastic Syndrome/Acute Myeloid Leukemia [see Warnings and Precautions (5.1)].
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Rubraca 600 mg twice daily as monotherapy, has been studied in 377 patients with ovarian cancer treated in two open-label, single arm trials. In these patients, the median age was 62 years (range 31 to 86), 100% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, 38% had BRCA-mutated ovarian cancer, 45% had received 3 or more prior lines of chemotherapy, and the median time since ovarian cancer diagnosis was 43 months (range 6 to 197).
Adverse reactions led to dose reduction or interruption in 62% of patients, most frequently from anemia (27%), and fatigue/asthenia (22%). Adverse reactions led to dose discontinuation in 10% of patients, most frequently from fatigue/asthenia (2%). The median duration of treatment was 5.5 months (range 0.1 to 28.0).
Table 2 and Table 3 summarize the common adverse reactions and abnormal laboratory findings, respectively, observed in patients treated with Rubraca.
The following adverse reactions have been identified in < 20% of the 377 patients treated with Rubraca 600 mg twice daily: dizziness (17%), neutropenia (15%), rash (includes rash, rash erythematous, rash maculopapular and dermatitis) (13%), pyrexia (11%), photosensitivity reaction (10%), pruritus (includes pruritus and pruritus generalized) (9%), Palmar-plantar erythrodysaesthesia syndrome (2%), and febrile neutropenia (1%).
8 USE IN SPECIFIC POPULATIONS
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