Perjeta Generic Name: pertuzumab Brand Name: Perjeta Drug Class: Perjeta (Pertuzumab) side effects drug center Related Drugs Arimidex Aromasin Capecitabine Tablets Cytoxan Ellence Faslodex Fosamax Fosamax Plus D Halotestin Herceptin Kisqali Kisqali FeMara Co-Pack Ontruzant Phesgo Piqray Talzenna Trodelvy Xeloda Health Resources Breast Cancer Mammogram PROFESSIONAL CONSUMER SIDE EFFECTS Overview Professional Information Perjeta Side Effects Center What Is Perjeta? Perjeta (pertuzumab) Injection is a monoclonal antibody used 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. What Are Side Effects of Perjeta? Common side effects of Perjeta include: heart problems, diarrhea, nausea, vomiting, tiredness, loss of appetite, dry skin, rash or itching, numbness or tingling in your hands or feet, or cold symptoms such as stuffy nose, sneezing, or sore throat Temporary hair loss may occur. Normal hair growth should return after treatment with Perjeta has ended. Dosage for Perjeta 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. What Drugs, Substances, or Supplements Interact with Perjeta? Perjeta may interact with other drugs. Tell your doctor all medications and supplements you use. Perjeta During Pregnancy and Breastfeeding Perjeta can cause serious (possibly fatal) harm to a fetus if used during pregnancy. Use 2 forms of birth control while using this medication and for 6 month after treatment has stopped. Consult your doctor to discuss birth control. If you are planning pregnancy, become pregnant, or think you may be pregnant, tell your doctor immediately. It is unknown if this drug passes into breast milk. Consult your doctor before breastfeeding. Additional Information Our Perjeta (pertuzumab) Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication. Perjeta Consumer Information Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Some side effects may occur during the injection. Tell your caregiver right away if you feel weak, tired, or nauseated, or if you have a fast heartbeat, headache, fever, chills, muscle pain, or an unusual taste in your mouth. Call your doctor at once if you have: dizziness, pounding heartbeats or fluttering in your chest; new or worsening cough or shortness of breath; swelling in your lower legs; low blood cell counts--fever, chills, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed; or signs of tumor cell breakdown--confusion, weakness, muscle cramps, nausea, vomiting, fast or slow heart rate, decreased urination, tingling in your hands and feet or around your mouth. Your cancer treatments may be delayed or permanently discontinued if you have certain side effects. Common side effects are more likely to occur, such as: nausea, diarrhea; temporary hair loss; fever, low blood cell counts; tiredness; rash; or numbness, tingling, or burning pain in your hands or feet. This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Read the entire detailed patient monograph for Perjeta (Pertuzumab) Perjeta Professional Information SIDE EFFECTS The following adverse reactions are discussed in greater detail in other sections of the label: Left Ventricular Dysfunction [see WARNINGS AND PRECAUTIONS] Embryo-Fetal Toxicity [see WARNINGS AND PRECAUTIONS] Infusion-Related Reactions [see WARNINGS AND PRECAUTIONS] Hypersensitivity Reactions/Anaphylaxis [see WARNINGS AND PRECAUTIONS] 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 2 were identified in 804 patients with HER2-positive metastatic breast cancer treated in CLEOPATRA. 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. Adverse reactions resulting in permanent discontinuation of all study therapy were 6% in the PERJETA-treated group and 5% for patients in the placebo-treated group. The most common adverse reactions (>1%) that led to discontinuation of all study therapy was left ventricular dysfunction (1% for patients in the PERJETA-treated group and 2% for patients in the placebo-treated group). The most common adverse reactions that led to discontinuation of docetaxel alone were edema, fatigue, edema peripheral, neuropathy peripheral, neutropenia, nail disorder and pleural effusion. Table 2 reports the adverse reactions that occurred in at least 10% of patients in the PERJETAtreated group. The safety profile of PERJETA remained unchanged with an additional 2.75 years of follow-up (median total follow-up of 50 months) in CLEOPATRA. 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 2: Summary of Adverse Reactions Occurring in ≥ 10% of Patients on the PERJETA Treatment Arm in CLEOPATRA 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 2 37 3 Mucosal inflammation 28 1 20 1 Asthenia 26 2 30 2 Edema peripheral 23 0.5 30 0.8 Pyrexia 19 1 18 0.5 Skin and subcutaneous tissue disorders Alopecia 61 0 60 0.3 Rash 34 0.7 24 0.8 Nail disorder 23 1 23 0.3 Pruritus 14 0 10 0 Dry skin 11 0 4 0 Gastrointestinal disorders Diarrhea 67 8 46 5 Nausea 42 1 42 0.5 Vomiting 24 1 24 2 Stomatitis 19 0.5 15 0.3 Constipation 15 0 25 1 Blood and lymphatic system disorders Neutropenia 53 49 50 46 Anemia 23 2 19 4 Leukopenia 18 12 20 15 Febrile neutropenia* 14 13 8 7 Nervous system disorders Neuropathy peripheral 32 3 34 2 Headache 21 1 17 0.5 Dysgeusia 18 0 16 0 Dizziness 13 0.5 12 0 Musculoskeletal and connective tissue disorders Myalgia 23 1 24 0.8 Arthralgia 15 0.2 16 0.8 Infections and infestations Upper respiratory tract infection 17 0.7 13 0 Nasopharyngitis 12 0 13 0.3 Respiratory, thoracic, and mediastinal disorders Dyspnea 14 1 16 2 Metabolism and nutrition disorders Decreased appetite 29 2 26 2 Eye disorders Lacrimation increased 14 0 14 0 Psychiatric disorders Insomnia 13 0 13 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 CLEOPATRA: Infections and Infestations Paronychia (7% in the PERJETA-treated group vs. 4% in the placebo-treated group) Adverse Reactions Reported in Patients Receiving PERJETA and Trastuzumab After Discontinuation of Docetaxel In CLEOPATRA, 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%), upper respiratory tract infection (13%), rash (12%), headache (11%), and fatigue (11%). Neoadjuvant Treatment Of Breast Cancer (NeoSphere) In NeoSphere, 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 CLEOPATRA. 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 3 reports the adverse reactions that occurred in patients who received neoadjuvant treatment with PERJETA for breast cancer in NeoSphere. Table 3 Summary of Adverse Reactions Occurring in ≥ 10% in the Neoadjuvant Setting for Patients Receiving PERJETA in NeoSphere 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 0 26 0.9 12 0 26 1 Mucosal inflammation 21 0 26 2 3 0 26 0 Asthenia 18 0 21 2 3 0 16 2 Pyrexia 10 0 17 0 8 0 9 0 Edema peripheral 10 0 3 0 0.9 0 5 0 Skin and subcutaneous tissue disorders Alopecia 66 0 65 0 3 0 67 0 Rash 21 2 26 0.9 11 0 29 1 Gastrointestinal disorders Diarrhea 34 4 46 6 28 0 54 4 Nausea 36 0 39 0 14 0 36 1 Stomatitis 7 0 18 0 5 0 10 0 Vomiting 12 0 13 0 5 0 16 2 Blood and lymphatic system disorders Neutropenia 64 59 50 45 0.9 0.9 65 57 Leukopenia 21 11 9 5 0 0 14 9 Nervous system disorders Dysgeusia 10 0 15 0 5 0 7 0 Headache 11 0 11 0 14 0 13 0 Peripheral Sensory Neuropathy 12 0.9 8 0.9 2 0 11 0 Musculoskeletal and connective tissue disorders Myalgia 22 0 22 0 9 0 21 0 Arthralgia 8 0 10 0 5 0 10 0 Metabolism and nutrition disorders Decreased appetite 7 0 14 0 2 0 15 0 Psychiatric disorders Insomnia 11 0 8 0 4 0 9 0 The following adverse reactions were reported in < 10% of patients receiving neoadjuvant treatment and occurred more frequently in PERJETA-treated groups in NeoSphere: (Ptz=pertuzumab; H=trastuzumab; D=docetaxel) Blood and Lymphatic System Disorders Anemia (7% in the H+D arm, 3% in the Ptz+H+D arm, 5% in the Ptz+H arm and 9% in the Ptz+D arm), Febrile neutropenia (7% in the H+D arm, 8% in the Ptz+H+D arm, 0% in the Ptz+H arm and 7% in the Ptz+D arm) Nervous System Disorders Dizziness (4% in the H+D arm, 3% in the Ptz+H+D arm, 6% in the Ptz+H arm and 3% in the Ptz+D arm) Infections and Infestations Upper respiratory tract infection (3% in the H+D arm, 5% in the Ptz+H+D arm, 2% in the Ptz+H arm and 7% in the Ptz+D arm) Eye Disorders Lacrimation increased (2% in the H+D arm, 4% in the Ptz+H+D arm, 0.9% in the Ptz+H arm, and 4% in the Ptz+D arm) Neoadjuvant Treatment Of Breast Cancer (TRYPHAENA) In TRYPHAENA, 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 NCICTCAE (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. Adverse reactions resulting in permanent discontinuation of any component of neoadjuvant treatment occurred in 7% of patients receiving PERJETA in combination with trastuzumab and docetaxel following FEC, and 8% for patients receiving PERJETA in combination with TCH. The most common adverse reactions (>2%) resulting in permanent discontinuation of PERJETA were left ventricular dysfunction, drug hypersensitivity, and neutropenia. Table 4 reports the adverse reactions that occurred in patients who received neoadjuvant treatment with PERJETA for breast cancer in TRYPHAENA. Table 4: Summary of Adverse Reactions Occurring in ≥ 10% of Patients Receiving Neoadjuvant Treatment with PERJETA in TRYPHAENA Body System/Adverse Reactions PERJETA + trastuzumab + FEC followed by PERJETA + trastuzumab + docetaxel vPERJETA + trastuzumab + docetaxel following FEC PERJETA + TCH n=72 n=75 n=76 Frequency rate % Frequency rate % 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 0 36 0 0 4 Mucosal inflammation 24 0 20 0 17 1 Pyrexia 17 0 9 0 16 0 Asthenia 10 0 15 1 13 1 Edema peripheral 11 0 4 0 9 0 Skin and subcutaneous tissue disorders Alopecia 49 0 52 0 55 0 Rash 19 0 11 0 21 1 Palmar-Plantar Erythrodysaesthesia Syndrome 7 0 11 0 8 0 Dry skin 6 0 9 0 11 0 Gastrointestinal disorders Diarrhea 61 4 61 5 72 12 Nausea 53 0 53 3 45 0 Vomiting 40 0 36 3 39 5 Dyspepsia 25 1 8 0 22 0 Constipation 18 0 23 0 16 0 Stomatitis 14 0 17 0 12 0 Blood and lymphatic system disorders Neutropenia 51 47 47 43 49 46 Leukopenia 22 19 16 12 17 12 Anemia 19 1 9 4 38 17 Febrile neutropenia 18 18 9 9 17 17 Thrombocytopenia` 7 0 1 0 30 12 Immune system disorders Hypersensitivity 10 3 1 0 12 3 Nervous system disorders Headache 22 0 15 0 17 0 Dysgeusia 11 0 13 0 21 0 Dizziness 8 0 8 1 16 0 Neuropathy peripheral 6 0 1 0 11 0 Musculoskeletal and connective tissue disorders Myalgia 17 0 11 1 11 0 Arthralgia 11 0 12 0 7 0 Respiratory, thoracic, and mediastinal disorders Dyspnea 13 0 8 3 11 1 Epistaxis 11 0 11 0 16 1 Cough 10 0 5 0 12 0 Oropharyngeal pain 8 0 7 0 12 0 Metabolism and nutrition disorders Decreased appetite 21 0 11 0 21 0 Eye disorders Lacrimation increased 13 0 5 0 8 0 Psychiatric disorders Insomnia 11 0 13 0 21 0 Investigations ALT increased 7 0 3 0 11 4 FEC=5-fluorouracil, epirubicin, cyclophosphamide, TCH=docetaxel, carboplatin, trastuzumab The following selected adverse reactions were reported in < 10% of patients receiving neoadjuvant treatment in TRYPHAENA: (Ptz=pertuzumab; H=trastuzumab; D=docetaxel; FEC= fluorouracil, epirubicin, and cyclophosphamide; TCH=docetaxel, carboplatin, and trastuzumab) Skin and Subcutaneous Tissue Disorders Nail disorder (10% in the Ptz+H+FEC/Ptz+H+D arm, 7% in the FEC/Ptz+H+D arm, and 9% in the Ptz+TCH arm), Paronychia (0% in the Ptz+H+FEC/Ptz+H+D arm, and 1% in both the FEC/Ptz+H+D and Ptz+TCH arms), Pruritus (3% in the Ptz+H+FEC/Ptz+H+D arm, 4% in the FEC/Ptz+H+D arm, and 4% in the Ptz+TCH arm) Infections and Infestations Upper respiratory tract infection (8.3% in the Ptz+H+FEC/Ptz+H+D arm, 4.0% in the FEC/Ptz+H+D arm, and 2.6% in the Ptz+TCH arm), Nasopharyngitis (6.9% in the Ptz+H+FEC/Ptz+H+D arm, 6.7% in the FEC/Ptz+H+D arm, and 7.9% in the Ptz+TCH arm) Neoadjuvant Treatment Of Breast Cancer (BERENICE) In BERENICE, when PERJETA was administered in combination with trastuzumab and paclitaxel for 4 cycles following 4 cycles of ddAC, the most common adverse reactions (> 30%) were nausea, diarrhea, alopecia, fatigue, constipation, peripheral neuropathy and headache. The most common Grade 3 – 4 adverse reactions (> 2%) were neutropenia, febrile neutropenia, neutrophil count decreased, white blood cell count decreased, anemia, diarrhea, peripheral neuropathy, alanine aminotransferase increased and nausea. When PERJETA was administered in combination with trastuzumab and docetaxel for 4 cycles following 4 cycles of FEC, the most common adverse reactions (> 30%) were diarrhea, nausea, alopecia, asthenia, constipation, fatigue, mucosal inflammation, vomiting, myalgia, and anemia. The most common Grade 3 – 4 adverse reactions (> 2%) were febrile neutropenia, diarrhea, neutropenia, neutrophil count decreased, stomatitis, fatigue, vomiting, mucosal inflammation, neutropenic sepsis and anemia. Adverse reactions resulting in permanent discontinuation of any component of neoadjuvant treatment were 14% for patients receiving PERJETA in combination with trastuzumab and paclitaxel following ddAC and 8% for patients receiving PERJETA in combination with trastuzumab and docetaxel following FEC. The most common adverse reactions (>1%) resulting in permanent discontinuation of any component of neoadjuvant treatment were neuropathy peripheral, ejection fraction decreased, diarrhea, neutropenia and infusion related reaction. Table 5 reports the adverse reactions that occurred in patients who received neoadjuvant treatment with PERJETA for breast cancer in BERENICE. Table 5: Summary of Adverse Reactions Occurring in ≥ 10% of Patients Receiving Neoadjuvant Treatment with PERJETA in BERENICE Body System/Adverse Reactions PERJETA + trastuzumab + paclitaxel following ddAC PERJETA + trastuzumab + docetaxel following FEC n=199 n=198 Frequency rate % Frequency rate % All Grades % Grades 3 – 4 % All Grades % Grades 3 – 4 % General disorders and administration site conditions Fatigue 58 1 1 5 Asthenia 19 2 41 0 Mucosal inflammation 22 1 37 4 Pyrexia 15 0 18 0 Edema peripheral 9 0 12 1 Skin and subcutaneous tissue disorders Alopecia 62 0 59 0 Rash 14 0 11 0 Dry skin 14 0 10 0 Nail discoloration 15 0 2 0 Palmar-Plantar Erythrodysaesthesia Syndrome 6 0 10 0.5 Gastrointestinal disorders Nausea 71 3 69 2 Diarrhea 67 3 69 10 Constipation 35 0.5 38 0.5 Vomiting 23 1 35 4 Stomatitis 25 0 27 5 Dyspepsia 19 0 16 0 Abdominal pain upper 6 0 13 0 Abdominal pain 5 0 10 0 Gastroesophageal reflux disease 12 0 2 0 Blood and lymphatic system disorders Anemia 27 3 30 3 Neutropenia 22 12 16 9 Febrile neutropenia 7 7 17 17 Nervous system disorders Headache 30 0.5 14 0.5 Dysgeusia 20 0 19 0.5 Neuropathy peripheral 42 3 26 0.5 Paresthesia 15 0 9 0 Dizziness 12 0 8 0 Musculoskeletal and connective tissue disorders Myalgia 20 0 33 1 Arthralgia 20 0 21 1 Back pain 10 0 9 0 Pain in extremity 10 0 8 0 Bone pain 12 0.5 5 0 Infections and infestations Urinary tract infection 11 1 2 0 Respiratory, thoracic, and mediastinal disorders Epistaxis 25 0 19 0 Dyspnea 15 0.5 15 0.5 Cough 20 0.5 9 0 Oropharyngeal pain 10 0 8 0.5 Metabolism and nutrition disorders Decreased appetite 20 0 23 0 Eye disorders Lacrimation increased 9 0 18 0 Psychiatric disorders Insomnia 19 0 13 0 Vascular disorders Hot flush 19 0 13 0 Investigations White blood cell count decreased 11 4 3 2 Injury, poisoning and procedural complications Infusion related reaction 16 1 13 1 ddAC = dose-dense doxorubicin, cyclophosphamide, FEC=5-fluorouracil, epirubicin, cyclophosphamide The following selected adverse reactions were reported in < 10% of patients receiving neoadjuvant treatment in BERENICE: (Ptz=pertuzumab; H=trastuzumab; P=paclitaxel; ddAC=dose-dense doxorubicin and cyclophosphamide; D=docetaxel; FEC= fluorouracil, epirubicin, and cyclophosphamide) Skin and Subcutaneous Tissue Disorders Pruritus (9% in the ddAC/Ptz+H+P arm, and 8% in the FEC/Ptz+H+D arm), Nail disorder (7% in the ddAC/Ptz+H+P arm, and 10% in the FEC/Ptz+H+D arm) Infections and Infestations Upper respiratory tract infection (7% in the ddAC/Ptz+H+P arm, and 2% in the FEC/Ptz+H+D arm), nasopharyngitis (7% in the ddAC/Ptz+H+P arm, and 9% in the FEC/Ptz+H+D arm), paronychia (0.5% in the ddAC/Ptz+H+P arm, and 1% in the FEC/Ptz+H+D arm) Adjuvant Treatment Of Breast Cancer (APHINITY) The adverse reactions described in Table 6 were identified in 4769 patients with HER2-positive early breast cancer treated in APHINITY. Patients were randomized to receive either PERJETA in combination with trastuzumab and chemotherapy or placebo in combination with trastuzumab and chemotherapy. Adverse reactions resulting in permanent discontinuation of any study therapy were 13% for patients in the PERJETA-treated group and 12% for patients in the placebo-treated group. Adverse reactions resulting in permanent discontinuation of PERJETA or placebo was 7% and 6%, respectively. The most common adverse reactions (>0.5%) resulting in permanent discontinuation of any study treatment were ejection fraction decreased, neuropathy peripheral, diarrhea, and cardiac failure. Table 6 reports the adverse reactions that occurred in at least 10% of patients in the PERJETA-treated group. When PERJETA was administered in combination with trastuzumab and chemotherapy, the most common adverse reactions (> 30%) were diarrhea, nausea, alopecia, fatigue, peripheral neuropathy, and vomiting. The most common Grade 3 – 4 adverse reactions (> 2%) were neutropenia, febrile neutropenia, diarrhea, neutrophil count decreased, anemia, white blood cell count decreased, leukopenia, fatigue, nausea, and stomatitis. The incidence of diarrhea, all Grades, was higher when chemotherapy was administered with targeted therapy (61% in the PERJETA-treated group vs. 34% in the placebo-treated group), and was higher when administered with non-anthracycline based therapy (85% in the PERJETAtreated group vs. 62% in the placebo-treated group) than with anthracycline based therapy (67% in the PERJETA-treated group vs. 41% in the placebo-treated group). The incidence of diarrhea during the period that targeted therapy was administered without chemotherapy was 18% in the PERJETA-treated group vs. 9% in the placebo-treated group. The median duration of all Grades diarrhea was 8 days for the PERJETA-treated group vs. 6 days for the placebo-treated group. The median duration of Grade ≥3 diarrhea was 20 days for the PERJETA-treated group vs. 8 days for the placebo-treated group. More patients required hospitalization for diarrhea as a serious adverse event in the PERJETA-treated group (2.4%) than in the placebo-treated group (0.7%). Table 6: Summary of Adverse Reactions Occurring in ≥ 10% of Patients Receiving Adjuvant Treatment with PERJETA in APHINITY Body System/ Adverse Reactions PERJETA + trastuzumab + chemotherapy n=2364 Frequency rate % Placebo + trastuzumab + chemotherapy n=2405 Frequency rate % All Grades % Grades 3 – 4 % All Grades % Grades 3 – 4 % General disorders and administration site conditions Fatigue 49 4 44 3 Mucosal inflammation 23 2 19 0.7 Asthenia 21 1 21 2 Pyrexia 20 0.6 20 0.7 Edema peripheral 17 0 0 0.2 Skin and subcutaneous tissue disorders Alopecia 67 <0.1 67 <0.1 Rash 26 0.4 20 0.2 Pruritus 14 0.1 9 <0.1 Dry skin 13 0.1 11 <0.1 Nail disorder 12 0.2 12 0.1 Gastrointestinal disorders Diarrhea 71 10 45 4 Nausea 69 2 65 2 Vomiting 32 2 30 2 Constipation 29 0.5 32 0.3 Stomatitis 28 2 24 1 Dyspepsia 14 0 14 0 Abdominal pain 12 0.5 11 0.6 Abdominal pain upper 10 0.3 9 0.2 Blood and lymphatic system disorders Anemia 28 7 23 5 Neutropenia 25 16 23 16 Febrile neutropenia* 12 12 11 11 Nervous system disorders Dysgeusia 26 0.1 22 <0.1 Neuropathy peripheral 33 1 32 1 Headache 22 0.3 23 0.4 Paresthesia 12 0.5 10 0.2 Dizziness 11 0 11 0.2 Musculoskeletal and connective tissue disorders Arthralgia 29 0.9 33 1 Myalgia 26 0.9 30 1 Pain in extremity 10 0.2 10 0.2 Infections and infestations Nasopharyngitis 13 <0.1 12 0.1 Respiratory, thoracic, and mediastinal disorders Epistaxis 18 <0.1 14 0 Cough 16 <0.1 15 <0.1 Dyspnea 12 0.4 12 0.5 Metabolism and nutrition disorders Decreased appetite 24 0.8 20 0.4 Vascular disorders Hot flush 20 0.2 21 0.4 Eye disorders Lacrimation increased 13 0 13 <0.1 Psychiatric disorders Insomnia 17 0.3 17 <0.1 Investigations Neutrophil count decreased 14 10 14 10 Injury, poisoning and procedural complications Radiation skin injury 13 0.3 11 0.3 * In this table this denotes an adverse reaction that has been reported in association with a fatal outcome For the adverse reactions that were reported in ≥10% of patients with at least 5% difference between the PERJETA-treated group and the placebo-treated group in APHINITY, the breakdown per chemotherapy regimen is provided: (Ptz=pertuzumab; H=trastuzumab; AC=anthracyclines; TCH=docetaxel, carboplatin, and trastuzumab) Gastrointestinal Disorders Diarrhea (67% in the Ptz+H+AC chemo arm, 85% in the Ptz+TCH arm, 41% in the Pla+H+AC chemo arm, 62% in the Pla+TCH arm) Skin and Subcutaneous Disorders Rash (26% in the Ptz+H+AC chemo arm, 25% in the Ptz+TCH arm, 21% in the Pla+H+AC chemo arm, 19% in the Pla+TCH arm), Pruritus (14% in the Ptz+H+AC chemo arm, 15% in the Ptz+TCH arm, 9% in the Pla+H+AC chemo arm, 9% in the Pla+TCH arm) The following clinically relevant adverse reactions were reported in < 10% of patients in the PERJETA-treated group in APHINITY: Blood and Lymphatic System Disorders Leukopenia (9% in the PERJETA-treated group vs. 9% in the placebo-treated group) Infections and Infestations Upper respiratory tract infection (8% in the PERJETA-treated group vs. 7% in the placebo-treated group), paronychia (4% in the PERJETA-treated group vs. 2% in the placebo-treated group) Adverse Reactions Reported in Patients Receiving PERJETA and Trastuzumab After Discontinuation of Chemotherapy In the APHINITY study, during the targeted treatment alone phase, all adverse reactions in the PERJETA treatment group occurred in < 10% of patients with the exception of diarrhea (18%), arthralgia (15%), radiation skin injury (12%), and hot flush (12%). Immunogenicity As with all therapeutic proteins, there is the potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to pertuzumab in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. Patients in CLEOPATRA were tested at multiple time-points for antibodies to PERJETA. 3% (13/389) of patients in the PERJETA-treated group and 7% (25/372) of patients in the placebotreated group tested positive for anti-PERJETA antibodies. Of these 38 patients, none experienced anaphylactic/hypersensitivity reactions that were clearly related to the anti-drug antibodies (ADA). The presence of pertuzumab in patient serum at the levels expected at the time of ADA 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. In the neoadjuvant period of BERENICE, 0.3% (1/383) of patients treated with PERJETA tested positive for anti-PERJETA antibodies. This patient did not experience any anaphylactic/hypersensitivity reactions. Post-Marketing Experience The following adverse reactions have been identified during post-approval use of PERJETA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Tumor lysis syndrome (TLS): Cases of possible TLS have been reported in patients treated with PERJETA. Patients with significant tumor burden (e.g., bulky metastases) may be at a higher risk. Patients could present with hyperuricemia, hyperphosphatemia, and acute renal failure which may represent possible TLS. Providers should consider additional monitoring and/or treatment as clinically indicated. Read the entire FDA prescribing information for Perjeta (Pertuzumab) &Copy; Perjeta Patient Information is supplied by Cerner Multum, Inc. and Perjeta Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
