Clinical Study CLEOPATRA
CLEOPATRA Was Designed to Demonstrate a Significant PFS and OS Benefit
Efficacy and safety of PERJETA studied in a large trial of first-line HER2+ MBC patients1
- CLEOPATRA was a multicenter, randomized, double-blind, placebo-controlled phase III trial
- Primary end point1
- Progression-free survival (PFS; as assessed by an independent review facility [IRF]), defined as time from randomization to documented progressive disease as determined by RECIST‖, or death
- Secondary end points1
- Overall survival (OS)
- Objective response rate (ORR)
- Duration of response (DoR)
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend pertuzumab (PERJETA®) + trastuzumab (Herceptin) + docetaxel as a (category-1) preferred option for the first-line treatment of patients with HER2-positive (HER2+) MBC4
Boxed WARNINGS: Left Ventricular Dysfunction and Embryo-Fetal Toxicity
PERJETA administration can result in subclinical and clinical cardiac failure manifesting as decreased LVEF and CHF. Evaluate cardiac function prior to and during treatment. Discontinue PERJETA treatment for a confirmed clinically significant decrease in left ventricular function.
Exposure to PERJETA can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception.
Please see additional select Important Safety Information throughout, and the accompanying full Prescribing Information including Boxed WARNINGS.
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PERJETA® (pertuzumab) is a HER2/neu receptor antagonist indicated in combination with Herceptin® (trastuzumab) and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.
Important Safety Information
Boxed WARNINGS: Left Ventricular Dysfunction and Embryo-Fetal Toxicity
- PERJETA administration can result in subclinical and clinical cardiac failure manifesting as decreased LVEF and CHF. Evaluate cardiac function prior to and during treatment. Discontinue PERJETA treatment for a confirmed clinically significant decrease in left ventricular function
- Exposure to PERJETA can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception
- Based on its mechanism of action and findings in animal studies, PERJETA can cause fetal harm when administered to a pregnant woman. PERJETA is a HER2/neu receptor antagonist. Cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death have been reported with use of another HER2/neu receptor antagonist (trastuzumab) during pregnancy. In an animal reproduction study, administration of pertuzumab to pregnant cynomolgus monkeys during the period of organogenesis resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal death at exposures 2.5 to 20 times the exposure in humans at the recommended dose, based on Cmax
- Verify the pregnancy status of females of reproductive potential prior to the initiation of PERJETA. Advise pregnant women and females of reproductive potential that exposure to PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception can result in fetal harm, including embryo-fetal death or birth defects. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of PERJETA in combination with trastuzumab
- There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to PERJETA during pregnancy. Encourage women who receive PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception, to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 or visiting http://www.motherpregnancyregistry.com/
- If PERJETA is administered during pregnancy, or if a patient becomes pregnant while receiving PERJETA or within 7 months following the last dose of PERJETA in combination with trastuzumab, health care providers and patients should immediately report PERJETA exposure to Genentech at 1-888-835-2555
Additional Important Safety Information
PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients.
Left Ventricular Dysfunction (LVD)
- In Study 1, for patients with MBC, PERJETA in combination with Herceptin and docetaxel was not associated with increases in the incidence of symptomatic left ventricular systolic dysfunction (LVSD) or decreases in left ventricular ejection fraction (LVEF) compared with placebo in combination with Herceptin and docetaxel
- Left ventricular dysfunction occurred in 4.4% of patients in the PERJETA-treated group and in 8.3% of patients in the placebo-treated group
- Symptomatic LVSD (congestive heart failure) occurred in 1.0% of patients in the PERJETA-treated group and in 1.8% of patients in the placebo-treated group
- Patients who have received prior anthracyclines or prior radiotherapy to the chest area may be at higher risk of decreased LVEF
- Assess LVEF prior to initiation of PERJETA and at regular intervals (eg, every 3 months in the metastatic setting) during treatment to ensure that LVEF is within your institution’s normal limits
- If LVEF is <45%, or is 45% to 49% with a 10% or greater absolute decrease below the pretreatment value, withhold PERJETA and Herceptin and repeat LVEF assessment within approximately 3 weeks. Discontinue PERJETA and Herceptin if LVEF has not improved or has declined further, unless benefits for the individual patient outweigh the risks
- PERJETA has been associated with infusion reactions
- In Study 1, for patients with MBC, on the first day, when only PERJETA was administered, the overall frequency of infusion reactions was 13.0% in the PERJETA-treated group and 9.8% in the placebo-treated group, with the majority being mild to moderate. The most common infusion reactions (≥1.0%) were pyrexia, chills, fatigue, headache, asthenia, hypersensitivity, and vomiting
- During the second cycle, when all drugs were administered on the same day, the most common infusion reactions in the PERJETA-treated group (≥1.0%) were fatigue, dysgeusia, hypersensitivity, myalgia, and vomiting
- Observe patients closely for 60 minutes after the first infusion and for 30 minutes after subsequent infusions of PERJETA. If a significant infusion reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies. Monitor patients carefully until complete resolution of signs and symptoms. Consider permanent discontinuation in patients with severe infusion reactions
- In Study 1, the overall frequency of hypersensitivity/anaphylaxis reactions was 10.8% in the PERJETA-treated group and 9.1% in the placebo-treated group. The incidence of Grades 3-4 hypersensitivity/anaphylaxis reactions was 2.0% in the PERJETA-treated group and 2.5% in the placebo-treated group according to NCI‑CTCAE (version 3). Overall, 4 patients in PERJETA-treated group and 2 patients in the placebo-treated group experienced anaphylaxis
- Patients should be observed closely for hypersensitivity reactions. Severe hypersensitivity, including anaphylaxis, has been observed in clinical trials with treatment of PERJETA. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients
- Detection of HER2 protein overexpression is necessary for selection of patients appropriate for PERJETA therapy because these are the only patients studied and for whom benefit has been shown
Most Common Adverse Reactions
In MBC, the most common adverse reactions (>30%) seen with PERJETA in combination with Herceptin and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy. The most common NCI-CTCAE (version 3) Grade 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, leukopenia, diarrhea, peripheral neuropathy, anemia, asthenia, and fatigue
Please see additional select Important Safety Information throughout, and the accompanying full Prescribing Information, including Boxed WARNINGS.
1. PERJETA Prescribing Information. Genentech, Inc., 2016. 2. Baselga J, Cortés J, Kim S-B, et al; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109-119. 3. HercepTest™ Interpretation Manual — Breast Cancer. USA: Dako; 2013. http://www.dako.com/us/29036_herceptest_interpretation_manual-breast_ihc_us.pdf. Accessed April 11, 2016. 4. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Breast Cancer. V.1.2016. http://www.nccn.org. Accessed April 11, 2016.