Dosage Form: injection, solution, concentrate
WARNING: EMBRYO-FETAL TOXICITY
Exposure to PERJETA can result in embryo-fetal death and birth defects. Studies in animals have resulted in oligohydramnios, delayed renal development, and death. Advise patients of these risks and the need for effective contraception. (5.1, 8.1, 8.6)
PERJETA is indicated for use in combination with 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.
Perjeta Injection Dosage and Administration
Recommended Doses and Schedules
The initial dose of PERJETA is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by a dose of 420 mg administered as an intravenous infusion over 30 to 60 minutes.
When administered with PERJETA, the recommended initial dose of trastuzumab is 8 mg/kg administered as a 90-minute intravenous infusion, followed every 3 weeks thereafter by a dose of 6 mg/kg administered as an intravenous infusion over 30 to 90 minutes.
When administered with PERJETA, the recommended initial dose of docetaxel is 75 mg/m2 administered as an intravenous infusion. The dose may be escalated to 100 mg/m2 administered every 3 weeks if the initial dose is well tolerated.
For delayed or missed doses, if the time between two sequential infusions is less than 6 weeks, the 420 mg dose of PERJETA should be administered. Do not wait until the next planned dose. If the time between two sequential infusions is 6 weeks or more, the initial dose of 840 mg PERJETA should be re-administered as a 60-minute intravenous infusion followed every 3 weeks thereafter by a dose of 420 mg administered as an intravenous infusion over 30 to 60 minutes.
The infusion rate of PERJETA may be slowed or interrupted if the patient develops an infusion-associated reaction. The infusion should be discontinued immediately if the patient experiences a serious hypersensitivity reaction [see Warnings and Precautions (5.2)].
Left Ventricular Ejection Fraction (LVEF):
Withhold PERJETA and trastuzumab dosing for at least 3 weeks for either:
- a drop in LVEF to less than 40% or
- LVEF of 40% to 45% with a 10% or greater absolute decrease below pretreatment values [see Warnings and Precautions (5.2)]
PERJETA may be resumed if the LVEF has recovered to greater than 45% or to 40% to 45% associated with less than a 10% absolute decrease below pretreatment values.
If after a repeat assessment within approximately 3 weeks, the LVEF has not improved, or has declined further, discontinuation of PERJETA and trastuzumab should be strongly considered, unless the benefits for the individual patient are deemed to outweigh the risks [see Warnings and Precautions (5.2)].
PERJETA should be withheld or discontinued if trastuzumab treatment is withheld or discontinued.
If docetaxel is discontinued, treatment with PERJETA and trastuzumab may continue.
Dose reductions are not recommended for PERJETA.
For docetaxel dose modifications, see docetaxel prescribing information.
Preparation for Administration
Administer as an intravenous infusion only. Do not administer as an intravenous push or bolus. Do not mix PERJETA with other drugs.
Prepare the solution for infusion, using aseptic technique, as follows:
- Parenteral drug products should be inspected visually for particulates and discoloration prior to administration.
- Withdraw the appropriate volume of PERJETA solution from the vial(s).
- Dilute into a 250 mL 0.9% sodium chloride PVC or non-PVC polyolefin infusion bag.
- Mix diluted solution by gentle inversion. Do not shake.
- Administer immediately once prepared.
- If the diluted infusion solution is not used immediately, it can be stored at 2°C to 8°C for up to 24 hours.
- Dilute with 0.9% Sodium Chloride injection only. Do not use dextrose (5%) solution.
Warnings and Precautions
PERJETA can cause fetal harm when administered to a pregnant woman. Treatment of pregnant cynomolgus monkeys with pertuzumab resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal death. If PERJETA is administered during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations (8.1)].
Verify pregnancy status prior to the initiation of PERJETA. Advise patients of the risks of embryo-fetal death and birth defects and the need for contraception during and after treatment. Advise patients to contact their healthcare provider immediately if they suspect they may be pregnant. If PERJETA is administered during pregnancy or if a patient becomes pregnant while receiving PERJETA, immediately report exposure to the Genentech Adverse Event Line at 1-888-835-2555. Encourage women who may be exposed during pregnancy to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 [see Patient Counseling Information (17)].
Monitor patients who become pregnant during PERJETA therapy for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care. The efficacy of intravenous hydration in the management of oligohydramnios due to PERJETA exposure is not known.
Left Ventricular Dysfunction
Decreases in LVEF have been reported with drugs that block HER2 activity, including PERJETA. In the randomized trial, PERJETA in combination with trastuzumab and docetaxel was not associated with increases in the incidence of symptomatic left ventricular systolic dysfunction (LVSD) or decreases in LVEF compared with placebo in combination with trastuzumab and docetaxel [see Clinical Studies (14.1)]. Left ventricular dysfunction occurred in 4.4% of patients in the PERJETA-treated group and 8.3% of patients in the placebo-treated group. Symptomatic left ventricular systolic dysfunction (congestive heart failure) occurred in 1.0% of patients in the PERJETA-treated group and 1.8% of patients in the placebo-treated group [see Adverse Reactions (6.1)]. Patients who have received prior anthracyclines or prior radiotherapy to the chest area may be at higher risk of decreased LVEF.
PERJETA has not been studied in patients with a pretreatment LVEF value of ≤ 50%, a prior history of CHF, decreases in LVEF to < 50% during prior trastuzumab therapy, or conditions that could impair left ventricular function such as uncontrolled hypertension, recent myocardial infarction, serious cardiac arrhythmia requiring treatment or a cumulative prior anthracycline exposure to > 360 mg/m2 of doxorubicin or its equivalent.
Assess LVEF prior to initiation of PERJETA and at regular intervals (e.g., every three months) during treatment to ensure that LVEF is within the institution's normal limits. If LVEF is < 40%, or is 40% to 45% with a 10% or greater absolute decrease below the pretreatment value, withhold PERJETA and trastuzumab and repeat LVEF assessment within approximately 3 weeks. Discontinue PERJETA and trastuzumab if the LVEF has not improved or has declined further, unless the benefits for the individual patient outweigh the risks [see Dosage and Administration (2.2)].
Infusion-Associated Reactions, Hypersensitivity Reactions/Anaphylaxis
PERJETA has been associated with infusion and hypersensitivity reactions [see Adverse Reactions (6.1)]. An infusion reaction was defined in the randomized trial as any event described as hypersensitivity, anaphylactic reaction, acute infusion reaction or cytokine release syndrome occurring during an infusion or on the same day as the infusion. The initial dose of PERJETA was given the day before trastuzumab and docetaxel to allow for the examination of PERJETA-associated reactions. 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. Less than 1% were grade 3 or 4. 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.
In the randomized trial, 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 Grade 3 – 4 hypersensitivity/anaphylaxis reactions was 2% in the PERJETA-treated group and 2.5% in the placebo-treated group according to National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI - CTCAE) (version 3). Overall, 4 patients in PERJETA-treated group and 2 patients in the placebo-treated group experienced anaphylaxis.
Observe patients closely for 60 minutes after the first infusion and for 30 minutes after subsequent infusions of PERJETA. If a significant infusion-associated 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 [see Dosage and Administration (2.2)].
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 [see Indications and Usage (1) and Clinical Studies (14)]. In the randomized trial, patients with breast cancer were required to have evidence of HER2 overexpression defined as 3+ IHC by Dako Herceptest™ or FISH amplification ratio ≥ 2.0 by Dako HER2 FISH PharmDx™ test kit. Only limited data were available for patients whose breast cancer was positive by FISH but did not demonstrate protein overexpression by IHC.
Assessment of HER2 status should be performed by laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance, including use of sub-optimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results.
The following adverse reactions are discussed in greater detail in other sections of the label:
- Embryo-Fetal Toxicity [see Warnings and Precautions (5.1)]
- Left Ventricular Dysfunction [see Warnings and Precautions (5.2)]
- Infusion-Associated Reactions, Hypersensitivity Reactions/Anaphylaxis [see Warnings and Precautions (5.3)]
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 clinical practice.
In clinical trials, PERJETA has been evaluated in more than 1400 patients with various malignancies and treatment with PERJETA was predominantly in combination with other anti-neoplastic agents.
The adverse reactions described in Table 1 were identified in 804 patients with HER2-positive metastatic breast cancer treated in the randomized trial. Patients were randomized to receive either PERJETA in combination with trastuzumab and docetaxel or placebo in combination with trastuzumab and docetaxel. The median duration of study treatment was 18.1 months for patients in the PERJETA-treated group and 11.8 months for patients in the placebo-treated group. No dose adjustment was permitted for PERJETA or trastuzumab. The rates of adverse events resulting in permanent discontinuation of all study therapy were 6.1% for patients in the PERJETA-treated group and 5.3% for patients in the placebo-treated group. Adverse events led to discontinuation of docetaxel alone in 23.6% of patients in the PERJETA-treated group and 23.2% of patients in the placebo-treated group. Table 1 reports the adverse reactions that occurred in at least 10% of patients in the PERJETA-treated group.
The most common adverse reactions (> 30%) seen with PERJETA in combination with trastuzumab 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. An increased incidence of febrile neutropenia was observed for Asian patients in both treatment arms compared with patients of other races and from other geographic regions. Among Asian patients, the incidence of febrile neutropenia was higher in the pertuzumab-treated group (26%) compared with the placebo-treated group (12%).
|Body System/Adverse Reactions||PERJETA |
|Frequency rate %||Frequency rate %|
3 – 4
3 – 4
|General disorders and administration site conditions|
|Skin and subcutaneous tissue disorders|
|Blood and lymphatic system disorders|
|Nervous system disorders|
|Musculoskeletal and connective tissue disorders|
|Infections and infestations|
|Upper respiratory tract infection||16.7||0.7||13.4||0.0|
|Respiratory, thoracic and mediastinal disorders|
|Metabolism and nutrition disorders|
The following clinically relevant adverse reactions were reported in < 10% of patients in the PERJETA-treated group:
Skin and subcutaneous tissue disorders: Paronychia (7.1% in the PERJETA-treated group vs. 3.5% in the placebo-treated group)
Respiratory, thoracic and mediastinal disorders: Pleural effusion (5.2% in the PERJETA-treated group vs. 5.8% in the placebo-treated group)
Cardiac disorders: Left ventricular dysfunction (4.4% in the PERJETA-treated group vs. 8.3% in the placebo-treated group) including symptomatic left ventricular systolic dysfunction (CHF) (1.0% in the PERJETA-treated group vs. 1.8% in the placebo-treated group)
Immune system disorders: Hypersensitivity (10.1% in the PERJETA-treated group vs. 8.6% in placebo-treated group)
Adverse Reactions Reported in Patients Receiving PERJETA and Trastuzumab after Discontinuation of Docetaxel
In the randomized trial, adverse reactions were reported less frequently after discontinuation of docetaxel treatment. All adverse reactions in the PERJETA and trastuzumab treatment group occurred in < 10% of patients with the exception of diarrhea (19.1%), upper respiratory tract infection (12.8%), rash (11.7%), headache (11.4%), and fatigue (11.1%).
As with all therapeutic proteins, there is the potential for an immune response to PERJETA.
Patients in the randomized trial were tested at multiple time-points for antibodies to PERJETA. Approximately 2.8% (11/386) of patients in the PERJETA-treated group and 6.2% (23/372) of patients in the placebo-treated group tested positive for anti-PERJETA antibodies. Of these 34 patients, none experienced anaphylactic/hypersensitivity reactions that were clearly related to the anti-therapeutic antibodies (ATA). The presence of pertuzumab in patient serum at the levels expected at the time of ATA sampling can interfere with the ability of this assay to detect anti-pertuzumab antibodies. In addition, the assay may be detecting antibodies to trastuzumab. As a result, data may not accurately reflect the true incidence of anti-pertuzumab antibody development.
Immunogenicity data are highly dependent on the sensitivity and specificity of the test methods used. Additionally, the observed incidence of a positive result in a test method may be influenced by several factors, including sample handling, timing of sample collection, drug interference, concomitant medication, and the underlying disease. For these reasons, comparison of the incidence of antibodies to PERJETA with the incidence of antibodies to other products may be misleading.
No drug-drug interactions were observed between pertuzumab and trastuzumab, or between pertuzumab and docetaxel.
USE IN SPECIFIC POPULATIONS
Pregnancy Category D
There are no adequate and well-controlled studies of PERJETA in pregnant women. Based on findings in animal studies, PERJETA can cause fetal harm when administered to a pregnant woman. The effects of PERJETA are likely to be present during all trimesters of pregnancy. Pertuzumab administered to pregnant cynomolgus monkeys resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal deaths at clinically relevant exposures of 2.5 to 20-fold greater than the recommended human dose, based on Cmax. If PERJETA is administered during pregnancy, or if a patient becomes pregnant while receiving PERJETA, the patient should be apprised of the potential hazard to the fetus.
If PERJETA is administered during pregnancy or if a patient becomes pregnant while receiving PERJETA, immediately report exposure to the Genentech Adverse Event Line at 1-888-835-2555. Encourage women who may be exposed during pregnancy to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 [see Patient Counseling Information (17)].
Reproductive toxicology studies have been conducted in cynomolgus monkeys. Pregnant monkeys were treated on Gestational Day (GD)19 with loading doses of 30 to 150 mg/kg pertuzumab, followed by bi-weekly doses of 10 to 100 mg/kg. These dose levels resulted in clinically relevant exposures of 2.5 to 20-fold greater than the recommended human dose, based on Cmax. Intravenous administration of pertuzumab from GD19 through GD50 (period of organogenesis) was embryotoxic, with dose-dependent increases in embryo-fetal death between GD25 to GD70. The incidences of embryo-fetal loss were 33, 50, and 85% for dams treated with bi-weekly pertuzumab doses of 10, 30, and 100 mg/kg, respectively (2.5 to 20-fold greater than the recommended human dose, based on Cmax). At Caesarean section on GD100, oligohydramnios, decreased relative lung and kidney weights and microscopic evidence of renal hypoplasia consistent with delayed renal development were identified in all pertuzumab dose groups. Pertuzumab exposure was reported in offspring from all treated groups, at levels of 29% to 40% of maternal serum levels at GD100.
It is not known whether PERJETA is excreted in human milk, but human IgG is excreted in human milk. Because many drugs are secreted in human milk and because of the potential for serious adverse reactions in nursing infants from PERJETA, a decision should be made whether to discontinue nursing, or discontinue drug, taking into account the elimination half-life of PERJETA and the importance of the drug to the mother [See Warnings and Precautions (5.1), Clinical Pharmacology (12.3)].
The safety and effectiveness of PERJETA have not been established in pediatric patients.
Of 402 patients who received PERJETA in the randomized trial, 60 patients (15%) were ≥ 65 years of age and 5 patients (1%) were ≥ 75 years of age. No overall differences in efficacy and safety of PERJETA were observed between these patients and younger patients.
Based on a population pharmacokinetic analysis, no significant difference was observed in the pharmacokinetics of pertuzumab between patients < 65 years (n=306) and patients ≥ 65 years (n=175).
Females of Reproductive Potential
PERJETA can cause embryo-fetal harm when administered during pregnancy. Counsel patients regarding pregnancy prevention and planning. Advise females of reproductive potential to use effective contraception while receiving PERJETA and for 6 months following the last dose of PERJETA.
If PERJETA is administered during pregnancy or if a patient becomes pregnant while receiving PERJETA, immediately report exposure to the Genentech Adverse Event Line at 1-888-835-2555. Encourage women who may be exposed during pregnancy to enroll in the MotHER Pregnancy Registry by contacting1-800-690-6720 [see Patient Counseling Information (17)].
Dose adjustments of PERJETA are not needed in patients with mild (creatinine clearance [CLcr] 60 to 90 mL/min) or moderate (CLcr 30 to 60 mL/min) renal impairment. No dose adjustment can be recommended for patients with severe renal impairment (CLcr less than 30 mL/min) because of the limited pharmacokinetic data available [see Clinical Pharmacology (12.3)].
Perjeta Injection Description
Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2). Pertuzumab is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture containing the antibiotic, gentamicin. Gentamicin is not detectable in the final product. Pertuzumab has an approximate molecular weight of 148 kDa.
PERJETA is a sterile, clear to slightly opalescent, colorless to pale brown liquid for intravenous infusion. Each single use vial contains 420 mg of pertuzumab at a concentration of 30 mg/mL in 20 mM L-histidine acetate (pH 6.0), 120 mM sucrose and 0.02% polysorbate 20.
Perjeta Injection - Clinical Pharmacology
Mechanism of Action
Pertuzumab targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2) and, thereby, blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3 and HER4. As a result, pertuzumab inhibits ligand-initiated intracellular signaling through two major signal pathways, mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase (PI3K). Inhibition of these signaling pathways can result in cell growth arrest and apoptosis, respectively. In addition, pertuzumab mediates antibody-dependent cell-mediated cytotoxicity (ADCC).
While pertuzumab alone inhibited the proliferation of human tumor cells, the combination of pertuzumab and trastuzumab significantly augmented anti-tumor activity in HER2-overexpressing xenograft models.
Pertuzumab demonstrated linear pharmacokinetics at a dose range of 2 – 25 mg/kg. Based on a population PK analysis that included 481 patients, the median clearance (CL) of pertuzumab was 0.24 L/day and the median half-life was 18 days. With an initial dose of 840 mg followed by a maintenance dose of 420 mg every three weeks thereafter, the steady-state concentration of pertuzumab was reached after the first maintenance dose.
The population PK analysis suggested no PK differences based on age, gender, and ethnicity (Japanese vs. non-Japanese). Baseline serum albumin level and lean body weight as covariates only exerted a minor influence on PK parameters. Therefore, no dose adjustments based on body weight or baseline albumin level are needed.
No drug-drug interactions were observed between pertuzumab and trastuzumab, or between pertuzumab and docetaxel in a sub-study of 37 patients in the randomized trial.
No dedicated renal impairment trial for PERJETA has been conducted. Based on the results of the population pharmacokinetic analysis, pertuzumab exposure in patients with mild (CLcr 60 to 90 mL/min, n=200) and moderate renal impairment (CLcr 30 to 60 mL/min, n=71) were similar to those in patients with normal renal function (CLcr greater than 90 mL/min, n=200). No relationship between CLcr and pertuzumab exposure was observed over the range of observed CLcr (27 to 244 mL/min).
The effect of pertuzumab with an initial dose of 840 mg followed by a maintenance dose of 420 mg every three weeks on QTc interval was evaluated in a subgroup of 20 patients with HER2-positive breast cancer in the randomized trial. No large changes in the mean QT interval (i.e., greater than 20 ms) from placebo based on Fridericia correction method were detected in the trial. A small increase in the mean QTc interval (i.e., less than 10 ms) cannot be excluded because of the limitations of the trial design.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of pertuzumab.
Studies have not been performed to evaluate the mutagenic potential of pertuzumab.
No specific fertility studies in animals have been performed to evaluate the effect of pertuzumab. No adverse effects on male and female reproductive organs were observed in repeat-dose toxicity studies of up to six months duration in cynomolgus monkeys.
Metastatic Breast Cancer
The randomized trial was a multicenter, double-blind, placebo-controlled trial of 808 patients with HER2-positive metastatic breast cancer. Breast tumor specimens were required to show HER2 overexpression defined as 3+ IHC or FISH amplification ratio ≥ 2.0 determined at a central laboratory. Patients were randomized 1:1 to receive placebo plus trastuzumab and docetaxel or PERJETA plus trastuzumab and docetaxel. Randomization was stratified by prior treatment (prior or no prior adjuvant/neoadjuvant anti-HER2 therapy or chemotherapy) and geographic region (Europe, North America, South America, and Asia). Patients with prior adjuvant or neoadjuvant therapy were required to have a disease-free interval of greater than 12 months before trial enrollment.
PERJETA was given intravenously at an initial dose of 840 mg, followed by 420 mg every 3 weeks thereafter. Trastuzumab was given intravenously at an initial dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks thereafter. Patients were treated with PERJETA and trastuzumab until progression of disease, withdrawal of consent, or unacceptable toxicity. Docetaxel was given as an initial dose of 75 mg/m2 by intravenous infusion every 3 weeks for at least 6 cycles. The docetaxel dose could be escalated to 100 mg/m2 at the investigator's discretion if the initial dose was well tolerated. At the time of the primary analysis, the mean number of cycles of study treatment administered was 16.2 in the placebo-treated group and 19.9 in the PERJETA-treated group.
The primary endpoint of the randomized trial was progression-free survival (PFS) as assessed by an independent review facility (IRF). PFS was defined as the time from the date of randomization to the date of disease progression or death (from any cause) if the death occurred within 18 weeks of the last tumor assessment. Additional endpoints included overall survival (OS), PFS (investigator-assessed), objective response rate (ORR) and duration of response.
Patient demographic and baseline characteristics were balanced between the treatment arms. The median age was 54 (range 22 to 89 years), 59% were White, 32% were Asian, and 4% were Black. All were women with the exception of 2 patients. Seventeen percent of patients were enrolled in North America, 14% in South America, 38% in Europe, and 31% in Asia. Tumor prognostic characteristics, including hormone receptor status (positive 48%, negative 50%), presence of visceral disease (78%) and non-visceral disease only (22%) were similar in the study arms. Approximately half of the patients received prior adjuvant or neoadjuvant anti-HER2 therapy or chemotherapy (placebo 47%, PERJETA 46%). Among patients with hormone receptor positive tumors, 45% received prior adjuvant hormonal therapy and 11% received hormonal therapy for metastatic disease. Eleven percent of patients received prior adjuvant or neoadjuvant trastuzumab.
The randomized trial demonstrated a statistically significant improvement in IRF-assessed PFS in the PERJETA-treated group compared with the placebo-treated group [hazard ratio (HR) = 0.62 (95% CI: 0.51, 0.75), p < 0.0001] and an increase in median PFS of 6.1 months (median PFS of 18.5 months in the PERJETA-treated group vs. 12.4 months in the placebo-treated group) (see Figure 1). The results for investigator-assessed PFS were comparable to those observed for IRF-assessed PFS.
Consistent results were observed across several patient subgroups including age (< 65 or ≥ 65 years), race, geographic region, prior adjuvant/neoadjuvant anti-HER2 therapy or chemotherapy (yes or no), and prior adjuvant/neoadjuvant trastuzumab (yes or no). In the subgroup of patients with hormone receptor-negative disease (n=408), the hazard ratio was 0.55 (95% CI: 0.42, 0.72). In the subgroup of patients with hormone receptor-positive disease (n=388), the hazard ratio was 0.72 (95% CI: 0.55, 0.95). In the subgroup of patients with disease limited to non-visceral metastasis (n=178), the hazard ratio was 0.96 (95% CI: 0.61, 1.52).
At the time of the PFS analysis, 165 patients had died. More deaths occurred in the placebo-treated group (23.6%) compared with the PERJETA-treated group (17.2%). At the interim OS analysis, the results were not mature and did not meet the pre-specified stopping boundary for statistical significance. See Table 2 and Figure 2.
|PERJETA + trastuzumab + docetaxel||Placebo + trastuzumab + docetaxel||HR|
|No. of patients with an event||191 (47.5%)||242 (59.6%)|
|No. of patients with an event||69 (17.2%)||96 (23.6%)|
|Objective Response Rate (ORR)|
|No. of patients analyzed|
|Objective response (CR + PR)||343||336|
|Complete response (CR)||275 (80.2%)||233 (69.3%)|
|Partial Response (PR)||19 (5.5%)||14 (4.2%)|
|256 (74.6%)||219 (65.2%)|
|Median Duration of Response (months)|
|Figure 1 Kaplan-Meier Curve of IRF-Assessed Progression-Free Survival for the Randomized Trial|
|Figure 2 Kaplan-Meier Curve of Overall Survival for the Randomized Trial|
How Supplied/Storage and Handling
PERJETA is supplied as a 420 mg/14 mL (30 mg/mL) single-use vial containing preservative-free solution. NDC 50242-145-01.
Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) until time of use.
Keep vial in the outer carton in order to protect from light.
DO NOT FREEZE. DO NOT SHAKE.
Patient Counseling Information
- Advise pregnant women and females of reproductive potential that PERJETA exposure can result in fetal harm, including embryo-fetal death or birth defects [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]
- Advise females of reproductive potential to use effective contraception while receiving PERJETA and for 6 months following the last dose of PERJETA [see Warnings and Precautions (5.1) and Use in Special Populations (8.6)]
- Advise nursing mothers treated with PERJETA to discontinue nursing or discontinue PERJETA, taking into account the importance of the drug to the mother [see Use in Specific Populations (8.3)].
- Encourage women who are exposed to PERJETA during pregnancy to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]
A Member of the Roche Group
1 DNA Way
South San Francisco, CA 94080-4990
U.S. License No. 1048
PERJETA is a trademark of Genentech, Inc.
©2012 Genentech, Inc.
Representative sample of labeling (see the HOW SUPPLIED section for complete listing):
PRINCIPAL DISPLAY PANEL - 30 mg/mL Vial Label
420 mg / 14 mL
(30 mg / mL)
Dilute Prior To Use
For Intravenous Infusion Only
Discard Unused Portion
pertuzumab injection, solution, concentrate
|Labeler - Genentech, Inc. (080129000)|
|Genentech, Inc. (Vacaville)||004074162||API MANUFACTURE(50242-145), ANALYSIS(50242-145)|
|Roche Diagnostics GmbH||315028860||MANUFACTURE(50242-145), ANALYSIS(50242-145)|
|F. Hoffmann-La Roche Ltd||485244961||LABEL(50242-145), PACK(50242-145)|
|Genentech, Inc. (Hillsboro)||833220176||LABEL(50242-145), PACK(50242-145)|
|Genentech, Inc. (SSF)||080129000||ANALYSIS(50242-145)|
|Genentech, Inc. (Oceanside)||146373191||ANALYSIS(50242-145)|
|Roche Singapore Technical Operations Pte. Ltd.||937189173||ANALYSIS(50242-145)|