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Perjeta

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Perjeta

Side Effects
Interactions

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the label:

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.

Metastatic Breast Cancer (MBC)

The adverse reactions described in Table 1 were identified in 804 patients with HER2-positive metastatic breast cancer treated in Study 1. 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 safety profile of PERJETA remained unchanged with an additional year of follow-up (median total follow-up of 30 months) in Study 1.

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 v3.0 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%).

 Table 1 : Summary of Adverse Reactions Occurring in ≥ 10% of Patients on the PERJETA Treatment Arm in Study 1

Body System/
Adverse Reactions
PERJETA + trastuzumab + docetaxel
n=407
Frequency rate %
Placebo + trastuzumab + docetaxel
n=397
Frequency rate %
All Grades % Grades 3 – 4 % All Grades % Grades 3 – 4 %
General disorders and administration site conditions
Fatigue 37.6 2.2 36.8 3.3
Asthenia 26 2.5 30.2 1.5
Edema peripheral 23.1 0.5 30 0.8
Mucosal inflammation 27.8 1.5 19.9 1
Pyrexia 18.7 1.2 17.9 0.5
Skin and subcutaneous tissue disorders
Alopecia 60.9 0 60.5 0.3
Rash 33.7 0.7 24.2 0.8
Nail disorder 22.9 1.2 22.9 0.3
Pruritus 14 0 10.1 0
Dry skin 10.6 0 4.3 0
Gastrointestinal disorders
Diarrhea 66.8 7.9 46.3 5
Nausea 42.3 1.2 41.6 0.5
Vomiting 24.1 1.5 23.9 1.5
Constipation 15 0 24.9 1
Stomatitis 18.9 0.5 15.4 0.3
Blood and lymphatic system disorders
Neutropenia 52.8 48.9 49.6 45.8
Anemia 23.1 2.5 18.9 3.5
Leukopenia 18.2 12.3 20.4 14.6
Febrile neutropenia* 13.8 13 7.6 7.3
Nervous system disorders
Neuropathy peripheral 32.4 3.2 33.8 2
Headache 20.9 1.2 16.9 0.5
Dysgeusia 18.4 0 15.6 0
Dizziness 12.5 0.5 12.1 0
Musculoskeletal and connective tissue disorders
Myalgia 22.9 1 23.9 0.8
Arthralgia 15.5 0.2 16.1 0.8
Infections and infestations
Upper respiratory tract infection 16.7 0.7 13.4 0
Nasopharyngitis 11.8 0 12.8 0.3
Respiratory, thoracic, and mediastinal disorders
Dyspnea 14 1 15.6 2
Metabolism and nutrition disorders
Decreased appetite 29.2 1.7 26.4 1.5
Eye disorders
Lacrimation increased 14 0 13.9 0
Psychiatric disorders
Insomnia 13.3 0 13.4 0
* In this table this denotes an adverse reaction that has been reported in association with a fatal outcome

The following clinically relevant adverse reactions were reported in < 10% of patients in the PERJETA-treated group in Study 1:

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 PERJETAtreated 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 Study 1, 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%).

Neoadjuvant Treatment of Breast Cancer (Study 2)

In Study 2, the most common adverse reactions seen with PERJETA in combination with trastuzumab and docetaxel administered for 4 cycles were similar to those seen in the PERJETAtreated group in Study 1. The most common adverse reactions ( > 30%) were alopecia, neutropenia, diarrhea, and nausea. The most common NCI - CTCAE v3.0 Grade 3 - 4 adverse reactions ( > 2%) were neutropenia, febrile neutropenia, leukopenia, and diarrhea. In this group, one patient permanently discontinued neoadjuvant treatment due to an adverse event. Table 2 reports the adverse reactions that occurred in patients who received neoadjuvant treatment with PERJETA for breast cancer in Study 2.

Table 2 : Summary of Adverse Reactions Occurring in ≥ 10% in the Neoadjuvant Setting for Patients Receiving PERJETA in Study 2

Body System/ Adverse Reactions Trastuzumab + docetaxel
n=107
Frequency rate %
PERJETA + trastuzumab + docetaxel
n=107
Frequency rate %
PERJETA + trastuzumab
n=108
Frequency rate %
PERJETA + docetaxel
n=108
Frequency rate %
All Grades % Grades 3 - 4 % All Grades % Grades 3 - 4 % All Grades % Grades 3 - 4 % All Grades % Grades 3 - 4 %
General disorders and administration site conditions
Fatigue 27.1 0.0 26.2 0.9 12.0 0.0 25.5 1.1
Asthenia 17.8 0.0 20.6 1.9 2.8 0.0 16.0 2.1
Edema peripheral 10.3 0.0 2.8 0.0 0.9 0.0 5.3 0.0
Mucosal inflammation 21.5 0.0 26.2 1.9 2.8 0.0 25.5 0.0
Pyrexia 10.3 0.0 16.8 0.0 8.3 0.0 8.5 0.0
Skin and subcutaneous tissue disorders
Alopecia 66.4 0.0 65.4 0.0 2.8 0.0 67.0 0.0
Rash 21.5 1.9 26.2 0.9 11.1 0.0 28.7 1.1
Gastrointestinal disorders
Diarrhea 33.6 3.7 45.8 5.6 27.8 0.0 54.3 4.3
Nausea 36.4 0.0 39.3 0.0 13.9 0.0 36.2 1.1
Vomiting 12.1 0.0 13.1 0.0 4.6 0.0 16.0 2.1
Stomatitis 7.5 0.0 17.8 0.0 4.6 0.0 9.6 0.0
Blood and lymphatic system disorders
Neutropenia 63.6 58.9 50.5 44.9 0.9 0.9 64.9 57.4
Leukopenia 21.5 11.2 9.3 4.7 0.0 0.0 13.8 8.5
Nervous system disorders
Headache 11.2 0.0 11.2 0.0 13.9 0.0 12.8 0.0
Dysgeusia 10.3 0.0 15.0 0.0 4.6 0.0 7.4 0.0
Peripheral Sensory Neuropathy 12.1 0.9 8.4 0.9 1.9 0.0 10.6 0.0
Musculoskeletal and connective tissue disorders
Myalgia 22.4 0.0 22.4 0.0 9.3 0.0 21.3 0.0
Arthralgia 8.4 0.0 10.3 0.0 4.6 0.0 9.6 0.0
Metabolism and nutrition disorders
Decreased appetite 6.5 0.0 14.0 0.0 1.9 0.0 14.9 0.0
Psychiatric disorders
Insomnia 11.2 0.0 8.4 0.0 3.7 0.0 8.5 0.0

The following adverse reactions were reported in < 10% of patients receiving neoadjuvant treatment and occurred more frequently in PERJETA-treated groups in Study 2: (Ptz=pertuzumab; T=trastuzumab; D=docetaxel)

Blood and lymphatic system disorders: Anemia (6.5% in the T+D arm, 2.8% in the Ptz+T+D arm, 4.6% in the Ptz+T arm and 8.5% in the Ptz+D arm), Febrile neutropenia (6.5% in the T+D arm, 8.4% in the Ptz+T+D arm, 0.0% in the Ptz+T arm and 7.4% in the Ptz+D arm)

Immune system disorders: Hypersensitivity (1.9% in the T+D arm, 5.6% in the Ptz+T+D arm, 5.6% in the Ptz+T arm and 5.3% in the Ptz+D arm)

Nervous system disorders: Dizziness (3.7% in the T+D arm, 2.8% in the Ptz+T+D arm, 5.6% in the Ptz+T arm and 3.2% in the Ptz+D arm)

Infections and infestations: Upper respiratory tract infection (2.8% in the T+D arm, 4.7% in the Ptz+T+D arm, 1.9% in the Ptz+T arm and 7.4% in the Ptz+D arm)

Respiratory, thoracic and mediastinal disorders: Dyspnea (3.7% in the T+D arm, 4.7% in the Ptz+T+D arm, 2.8% in the Ptz+T arm and 2.1% in the Ptz+D arm)

Cardiac disorders: Left ventricular dysfunction (0.9% in the T+D arm, 2.8% in the Ptz+T+D arm, 0.0% in the Ptz+T arm, and 1.1% in the Ptz+D arm) including symptomatic left ventricular dysfunction (CHF) (0.9% in the Ptz+T arm and 0.0% in the T+D arm, Ptz+T+D arm, and Ptz+D arm)

Eye disorders: Lacrimation increased (1.9% in the T+D arm, 3.7% in the Ptz+T+D arm, 0.9% in the Ptz+T arm, and 4.3% in the Ptz+D arm)

Neoadjuvant Treatment of Breast Cancer (Study 3)

In Study 3, when PERJETA was administered in combination with trastuzumab and docetaxel for 3 cycles following 3 cycles of FEC, the most common adverse reactions ( > 30%) were diarrhea, nausea, alopecia, neutropenia, vomiting, and fatigue. The most common NCI-CTCAE (version 3) Grade 3 - 4 adverse reactions ( > 2%) were neutropenia, leukopenia, febrile neutropenia, diarrhea, left ventricular dysfunction, anemia, dyspnea, nausea, and vomiting.

Similarly, when PERJETA was administered in combination with docetaxel, carboplatin, and trastuzumab (TCH) for 6 cycles, the most common adverse reactions ( > 30%) were diarrhea, alopecia, neutropenia, nausea, fatigue, vomiting, anemia, and thrombocytopenia. The most common NCI-CTCAE (version 3) Grade 3 - 4 adverse reactions ( > 2%) were neutropenia, febrile neutropenia, anemia, leukopenia, diarrhea, thrombocytopenia, vomiting, fatigue, ALT increased, hypokalemia, and hypersensitivity.

The rates of adverse events resulting in permanent discontinuation of any component of neoadjuvant treatment were 6.7% for patients receiving PERJETA in combination with trastuzumab and docetaxel following FEC and 7.9% for patients receiving PERJETA in combination with TCH. Table 3 reports the adverse reactions that occurred in patients who received neoadjuvant treatment with PERJETA for breast cancer in Study 3.

Table 3 : Summary of Adverse Reactions Occurring in ≥ 10% of Patients Receiving Neoadjuvant Treatment with PERJETA in Study 3

Body System/Adverse Reactions PERJETA + trastuzumab + FEC followed by PERJETA + trastuzumab + docetaxel
n=72
Frequency rate %
PERJETA + trastuzumab + docetaxel following FEC
n=75
Frequency rate %
PERJETA + TCH
n=76
Frequency rate %
All Grades % Grades 3 - 4 % All Grades % Grades 3 - 4 % All Grades % Grades 3 - 4 %
General disorders and administration site conditions
Fatigue 36.1 0.0 36.0 0.0 42.1 3.9
Asthenia 9.7 0.0 14.7 1.3 13.2 1.3
Edema peripheral 11.1 0.0 4.0 0.0 9.2 0.0
Mucosal inflammation 23.6 0.0 20.0 0.0 17.1 1.3
Pyrexia 16.7 0.0 9.3 0.0 15.8 0.0
Skin and subcutaneous tissue disorders
Alopecia 48.6 0.0 52.0 0.0 55.3 0.0
Rash 19.4 0.0 10.7 0.0 21.1 1.3
Dry skin 5.6 0.0 9.3 0.0 10.5 0.0
Palmar-Plantar Erythrodysaesthesia Syndrome 6.9 0.0 10.7 0.0 7.9 0.0
Gastrointestinal disorders
Diarrhea 61.1 4.2 61.3 5.3 72.4 11.8
Dyspepsia 25.0 1.4 8 0.0 22.4 0.0
Nausea 52.8 0.0 53.3 2.7 44.7 0.0
Vomiting 40.3 0.0 36.0 2.7 39.5 5.3
Constipation 18.1 0.0 22.7 0.0 15.8 0.0
Stomatitis 13.9 0.0 17.3 0.0 11.8 0.0
Blood and lymphatic system disorders
Neutropenia 51.4 47.2 46.7 42.7 48.7 46.1
Anemia 19.4 1.4 9.3 4.0 38.2 17.1
Leukopenia 22.2 19.4 16.0 12.0 17.1 11.8
Febrile neutropenia 18.1 18.1 9.3 9.3 17.1 17.1
Thromb ocytopenia 6.9 0.0 1.3 0.0 30.3 11.8
Immune system disorders
Hypersensitivity 9.7 2.8 1.3 0.0 11.8 2.6
Nervous system disorders
Neuropathy peripheral 5.6 0.0 1.3 0.0 10.5 0.0
Headache 22.2 0.0 14.7 0.0 17.1 0.0
Dysgeusia 11.1 0.0 13.3 0.0 21.1 0.0
Dizziness 8.3 0.0 8.0 1.3 15.8 0.0
Musculoskeletal and connective tissue disorders
Myalgia 16.7 0.0 10.7 1.3 10.5 0.0
Arthralgia 11.1 0.0 12.0 0.0 6.6 0.0
Respiratory, thoracic, and mediastinal disorders
Cough 9.7 0.0 5.3 0.0 11.8 0.0
Dyspnea 12.5 0.0 8.0 2.7 10.5 1.3
Epistaxis 11.1 0.0 10.7 0.0 15.8 1.3
Oropharyngeal pain 8.3 0.0 6.7 0.0 11.8 0.0
Metabolism and nutrition disorders
Decreased appetite 20.8 0.0 10.7 0.0 21.1 0.0
Eye disorders
Lacrimation increased 12.5 0.0 5.3 0.0 7.9 0.0
Psychiatric disorders
Insomnia 11.1 0.0 13.3 0.0 21.1 0.0
Investigations
ALT increased 6.9 0.0 2.7 0.0 10.5 3.9
FEC=5-fluorouracil, epirubicin, cyclophosphamide, TCH=docetaxel, carboplatin, trastuzumab

The following selected adverse reactions were reported in < 10% of patients receiving neoadjuvant treatment in Study 3: (Ptz=pertuzumab; T=trastuzumab; D=docetaxel; FEC= fluorouracil, epirubicin, and cyclophosphamide; TCH=docetaxel, carboplatin, and trastuzumab)

Skin and subcutaneous tissue disorders: Nail disorder (9.7% in the Ptz+T+FEC/Ptz+T+D arm, 6.7% in the FEC/Ptz+T+D arm, and 9.2% in the Ptz+TCH arm), Paronychia (0% in the Ptz+T+FEC/Ptz+T+D and 1.3% in both the FEC/Ptz+T+D and Ptz+TCH arms), Pruritis (2.8% in the Ptz+T+FEC/Ptz+T+D arm, 4.0% in the FEC/Ptz+T+D arm, and 3.9% in the Ptz+TCH arm)

Infections and infestations: Upper respiratory tract infection (8.3% in the Ptz+T+FEC/Ptz+T+D arm, 4.0% in the FEC/Ptz+T+D arm, and 2.6% in the Ptz+TCH arm), Nasopharyngitis (6.9% in the Ptz+T+FEC/Ptz+T+D arm, 6.7% in the FEC/Ptz+T+D arm, and 7.9% in the Ptz+TCH arm)

Respiratory, thoracic, and mediastinal disorders: Pleural effusion (1.4% in the Ptz+T+FEC/Ptz+T+D arm and 0% in the FEC/Ptz+T+D and Ptz+TCH arm)

Cardiac disorders: Left ventricular dysfunction (5.6% in the Ptz+T+FEC/PTZ+T+D arm, 4.0% in the FEC/Ptz+T+D arm, and 2.6% in the Ptz+TCH arm) including symptomatic left ventricular systolic dysfunction (CHF) (2.7% in the FEC/Ptz+T+D arm and 0% in the Ptz+T+FEC/Ptz+T+D and Ptz+TCH arms)

Immunogenicity

As with all therapeutic proteins, there is the potential for an immune response to PERJETA.

Patients in Study 1 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 antipertuzumab 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.

Read the Perjeta (pertuzumab) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

No drug-drug interactions were observed between pertuzumab and trastuzumab, or between pertuzumab and docetaxel.

Last reviewed on RxList: 10/18/2013
This monograph has been modified to include the generic and brand name in many instances.

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