Phesgo
Generic: PERTUZUMAB, TRASTUZUMAB, AND HYALURONIDASE-ZZXF
Basic Information
Manufacturer
Genentech, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
SUBCUTANEOUS
FDA Set ID
27dd5e6b-72cd-458d-a015-cf4dab5800da
Indications & Usage
1 INDICATIONS AND USAGE PHESGO is a combination of pertuzumab and trastuzumab, HER2/neu receptor antagonists, and hyaluronidase, an endoglycosidase, indicated for: Use in combination with chemotherapy as: neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer.
( 1.1 ) adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence ( 1.1 ) Use in combination with docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.
( 1.2 ) 1.1 Early Breast Cancer (EBC) PHESGO is indicated for use in combination with chemotherapy for the neoadjuvant treatment of adult patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer [see Dosage and Administration (2.2) and Clinical Studies (14.2) ] .
the adjuvant treatment of adult patients with HER2-positive early breast cancer at high risk of recurrence [see Dosage and Administration (2.2) and Clinical Studies (14.2) ] .
Select patients for therapy based on an FDA-authorized companion diagnostic test [see Dosage and Administration (2.1) ].
1.2 Metastatic Breast Cancer (MBC) PHESGO is indicated for use in combination with docetaxel for the treatment of adult patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease [see Dosage and Administration (2.2) and Clinical Studies (14.1) ] .
Select patients for therapy based on an FDA-authorized companion diagnostic test [see Dosage and Administration (2.1) ].
( 1.1 ) adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence ( 1.1 ) Use in combination with docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.
( 1.2 ) 1.1 Early Breast Cancer (EBC) PHESGO is indicated for use in combination with chemotherapy for the neoadjuvant treatment of adult patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer [see Dosage and Administration (2.2) and Clinical Studies (14.2) ] .
the adjuvant treatment of adult patients with HER2-positive early breast cancer at high risk of recurrence [see Dosage and Administration (2.2) and Clinical Studies (14.2) ] .
Select patients for therapy based on an FDA-authorized companion diagnostic test [see Dosage and Administration (2.1) ].
1.2 Metastatic Breast Cancer (MBC) PHESGO is indicated for use in combination with docetaxel for the treatment of adult patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease [see Dosage and Administration (2.2) and Clinical Studies (14.1) ] .
Select patients for therapy based on an FDA-authorized companion diagnostic test [see Dosage and Administration (2.1) ].
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Cardiomyopathy [see Warnings and Precautions (5.1) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.2) ] Pulmonary Toxicity [see Warnings and Precautions (5.3) ] Exacerbation of Chemotherapy-Induced Neutropenia [see Warnings and Precautions (5.4) ] Hypersensitivity and Administration-Related Reactions [see Warnings and Precautions (5.5) ] Neoadjuvant and Adjuvant Treatment of Breast Cancer The most common adverse reactions (>30%) with PHESGO were alopecia, nausea, diarrhea, anemia, and asthenia.
( 6.1 ) Metastatic Breast Cancer (based on intravenous pertuzumab ) The most common adverse reactions (> 30%) with pertuzumab in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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.
Neoadjuvant and Adjuvant Treatment of Breast Cancer The safety of PHESGO was evaluated in an open-label, multicenter, randomized trial (FeDeriCa) conducted in 500 patients with HER2 overexpressing early breast cancer [see Clinical Studies (14.2) ] .
Patients were randomized to receive either PHESGO (1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase/15 mL) followed every 3 weeks by a maintenance dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase/10 mL or the recommended dosages for intravenous pertuzumab and intravenous trastuzumab.
Patients were randomized to receive 8 cycles of neoadjuvant chemotherapy with concurrent administration of 4 cycles of either PHESGO or intravenous pertuzumab and trastuzumab during cycles 5-8, followed by surgery.
Following surgery, patients continued therapy with PHESGO alone or intravenous pertuzumab and trastuzumab (intravenous or subcutaneously administered) as treated prior to surgery, for an additional 14 cycles, to complete 18 cycles.
The median duration of treatment for PHESGO was 24 weeks (range: 0-42 weeks).
Serious adverse reactions occurred in 16% of patients who received PHESGO.
Serious adverse reactions in > 1% of patients included febrile neutropenia (4%), neutropenic sepsis (1%), and neutrophil count decreased (1%).
One fatal adverse reaction occurred in 1/248 (0.4%) of patients, which was due to acute myocardial infarction, and occurred prior to the start of HER2 targeted treatment with PHESGO.
Adverse reactions resulting in permanent discontinuation of any study drug occurred in 8% of patients on the PHESGO arm.
Adverse reactions which resulted in permanent discontinuation of PHESGO were ejection fraction decreased (1.2%), cardiac failure (0.8%), and pneumonitis/pulmonary fibrosis (0.8%).
Dosage interruptions due to an adverse reaction occurred in 40% of patients who received PHESGO.
Adverse reactions which required dosage interruption in > 1% of patients who received PHESGO included neutropenia (8%), neutrophil count decreased (4%), and diarrhea (7%).
Table 3 summarizes the adverse reactions in FeDeriCa.
Table 3: Adverse Reactions (≥5%) in Patients Who Received PHESGO in FeDeriCa Adverse Reactions PHESGO (n=248) Intravenous pertuzumab plus intravenous or subcutaneous trastuzumab (n=252) All Grades % Grades 3 – 4 % All Grades % Grades 3 – 4 % Skin and subcutaneous tissue disorders Alopecia 77 0 71 0.4 Dry skin 15 0.4 13 0 Rash 16 0.4 21 0 Nail discoloration 9 0 6 0 Erythema 9 0 5 0 Dermatitis 7 0 6 0 Nail disorder 7 0 7 0.4 Palmar-plantar erythrodysaesthesia syndrome 6 0.8 5 0.4 Gastrointestinal disorders Nausea 60 2 61 1.6 Diarrhea 60 7 57 4.8 Stomatitis 25 0.8 24 0.8 Constipation 22 0 21 0 Vomiting 20 0.8 19 1.2 Dyspepsia 14 0 12 0 Hemorrhoids 9 0 4.0 0 Abdominal pain upper 8 0 6 0 Abdominal pain 9 0.4 6 0 Blood and lymphatic system disorders Anemia 36 1.6 43 4.4 Neutropenia 22 14 27 14 Leukopenia 9 2.4 14 2 Febrile neutropenia 7 7 6 6 General disorders and administration site conditions Asthenia 31 0.4 32 2.4 Fatigue 29 2 24 2 Mucosal inflammation 15 0.8 20 1.2 Injection site reaction 15 0 0.8 0 Pyrexia 13 0 16 0.4 Edema peripheral 8 0 10 0 Malaise 7 0 6 0.4 Influenza-like illness 5 0 3.6 0 Nervous system disorders Dysgeusia 17 0 14 0 Peripheral sensory neuropathy 16 0.8 14 0.4 Headache 17 0 25 0.8 Neuropathy peripheral 12 0.4 15 2 Paresthesia 10 0.8 8 0 Dizziness 13 0 11 0 Investigations Weight decreased 11 0.8 6 0.8 Musculoskeletal and connective tissue disorders Myalgia 25 0.4 19 0.4 Arthralgia 24 0 28 0.4 Back pain 10 0 4.8 0 Bone pain 7 0 5 0 Pain in extremity 6 0 8 0 Muscle spasms 6 0 7 0 Musculoskeletal pain 6 0.4 8 0 Respiratory, thoracic and mediastinal disorder Cough 15 0.4 13 0 Epistaxis 12 0 14 0.4 Dyspnea 10 1.2 5 0 Rhinorrhea 7 0 4.4 0 Infections and infestations Upper respiratory tract infection 11 0 8 0.8 Nasopharyngitis 9 0 10 0 Paronychia 7 0.4 3.6 0 Urinary tract infection 7 0.4 5 0 Injury, poisoning and procedural complications Procedural pain 13 0 10 0 Radiation skin injury 19 0.4 19 0.4 Infusion related reaction 3.6 0 15 0.8 Metabolism and nutrition disorders Decreased appetite 17 0.8 19 0.4 Hypokalemia 7 1.6 8 0 Psychiatric disorders Insomnia 17 0 13 0.4 Eye disorders Lacrimation increased 5 0.4 6 0 Dry eye 5 0.4 3.2 0 Vascular disorders Hot flush 12 0 13 0 Clinically relevant adverse reactions in <5% of patients who received PHESGO include ejection fraction decreased (3.6%) and pruritus (3.2%).
In the FeDeriCa trial, when PHESGO was administered alone, adverse reactions occurred in <10% of patients with the exception of radiation skin injury (20%), arthralgia (19%), diarrhea (17%), injection site reaction (13%), dyspepsia (12%), asthenia (11%), hot flush (11%), and pruritus (10%).
Table 4 summarizes the laboratory abnormalities in FeDeriCa.
Table 4: Select Laboratory Abnormalities (≥5%) that Worsened from Baseline in Patients Who Received PHESGO in FeDeriCa The denominator used to calculate the rate varied from 163 to 252 based on the number of patients with a baseline value and at least one post-treatment value.
Laboratory Abnormality PHESGO (n=248) Intravenous pertuzumab plus intravenous or subcutaneous trastuzumab (n=252) All Grades % Grades 3 – 4 % All Grades % Grades 3 – 4 % Hematology Hemoglobin (low) 90 2.8 92 4.4 Lymphocytes, Absolute (low) 89 37 88 36 Total Leukocyte Count (low) 82 25 78 25 Neutrophils, Total Absolute (low) 68 30 67 33 Platelet (low) 27 0 28 0.4 Chemistry Creatinine (high) 84 0 87 0.4 Alanine aminotransferase (high) 58 1.6 68 2.4 Aspartate aminotransferase (high) 50 0.8 58 0.8 Potassium (low) 17 5.2 17 2.8 Albumin (low) 16 0 20 0.4 Potassium (high) 13 1.2 9 0 Sodium (low) 13 0.4 10 1.6 Bilirubin (high) 9 0 9 0.4 Glucose (low) 9 0 9 0.4 Sodium (high) 7 0.8 10 0.8 Other Clinical Trials Experience The safety of the addition of intravenous pertuzumab to trastuzumab in combination with chemotherapy has been established in studies conducted in patients with HER2 overexpressing early breast cancer.
The following adverse reactions have been reported following administration of intravenous pertuzumab and trastuzumab: diarrhea, alopecia, nausea, fatigue, neutropenia, vomiting, peripheral neuropathy, constipation, anemia, asthenia, mucosal inflammation, myalgia, and thrombocytopenia.
Refer to the Prescribing Information for pertuzumab for more information.
The safety of intravenous pertuzumab, trastuzumab and docetaxel has been established in patients with HER2 overexpressing metastatic breast cancer.
The following adverse reactions have been reported following administration of intravenous pertuzumab and trastuzumab: diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy.
Refer to the Prescribing Information for pertuzumab for more information.
6.2 Postmarketing Experience The following adverse reactions have been identified with the use of intravenous trastuzumab.
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.
Glomerulopathy Immune thrombocytopenia Tumor lysis syndrome (TLS): 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.
( 6.1 ) Metastatic Breast Cancer (based on intravenous pertuzumab ) The most common adverse reactions (> 30%) with pertuzumab in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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.
Neoadjuvant and Adjuvant Treatment of Breast Cancer The safety of PHESGO was evaluated in an open-label, multicenter, randomized trial (FeDeriCa) conducted in 500 patients with HER2 overexpressing early breast cancer [see Clinical Studies (14.2) ] .
Patients were randomized to receive either PHESGO (1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase/15 mL) followed every 3 weeks by a maintenance dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase/10 mL or the recommended dosages for intravenous pertuzumab and intravenous trastuzumab.
Patients were randomized to receive 8 cycles of neoadjuvant chemotherapy with concurrent administration of 4 cycles of either PHESGO or intravenous pertuzumab and trastuzumab during cycles 5-8, followed by surgery.
Following surgery, patients continued therapy with PHESGO alone or intravenous pertuzumab and trastuzumab (intravenous or subcutaneously administered) as treated prior to surgery, for an additional 14 cycles, to complete 18 cycles.
The median duration of treatment for PHESGO was 24 weeks (range: 0-42 weeks).
Serious adverse reactions occurred in 16% of patients who received PHESGO.
Serious adverse reactions in > 1% of patients included febrile neutropenia (4%), neutropenic sepsis (1%), and neutrophil count decreased (1%).
One fatal adverse reaction occurred in 1/248 (0.4%) of patients, which was due to acute myocardial infarction, and occurred prior to the start of HER2 targeted treatment with PHESGO.
Adverse reactions resulting in permanent discontinuation of any study drug occurred in 8% of patients on the PHESGO arm.
Adverse reactions which resulted in permanent discontinuation of PHESGO were ejection fraction decreased (1.2%), cardiac failure (0.8%), and pneumonitis/pulmonary fibrosis (0.8%).
Dosage interruptions due to an adverse reaction occurred in 40% of patients who received PHESGO.
Adverse reactions which required dosage interruption in > 1% of patients who received PHESGO included neutropenia (8%), neutrophil count decreased (4%), and diarrhea (7%).
Table 3 summarizes the adverse reactions in FeDeriCa.
Table 3: Adverse Reactions (≥5%) in Patients Who Received PHESGO in FeDeriCa Adverse Reactions PHESGO (n=248) Intravenous pertuzumab plus intravenous or subcutaneous trastuzumab (n=252) All Grades % Grades 3 – 4 % All Grades % Grades 3 – 4 % Skin and subcutaneous tissue disorders Alopecia 77 0 71 0.4 Dry skin 15 0.4 13 0 Rash 16 0.4 21 0 Nail discoloration 9 0 6 0 Erythema 9 0 5 0 Dermatitis 7 0 6 0 Nail disorder 7 0 7 0.4 Palmar-plantar erythrodysaesthesia syndrome 6 0.8 5 0.4 Gastrointestinal disorders Nausea 60 2 61 1.6 Diarrhea 60 7 57 4.8 Stomatitis 25 0.8 24 0.8 Constipation 22 0 21 0 Vomiting 20 0.8 19 1.2 Dyspepsia 14 0 12 0 Hemorrhoids 9 0 4.0 0 Abdominal pain upper 8 0 6 0 Abdominal pain 9 0.4 6 0 Blood and lymphatic system disorders Anemia 36 1.6 43 4.4 Neutropenia 22 14 27 14 Leukopenia 9 2.4 14 2 Febrile neutropenia 7 7 6 6 General disorders and administration site conditions Asthenia 31 0.4 32 2.4 Fatigue 29 2 24 2 Mucosal inflammation 15 0.8 20 1.2 Injection site reaction 15 0 0.8 0 Pyrexia 13 0 16 0.4 Edema peripheral 8 0 10 0 Malaise 7 0 6 0.4 Influenza-like illness 5 0 3.6 0 Nervous system disorders Dysgeusia 17 0 14 0 Peripheral sensory neuropathy 16 0.8 14 0.4 Headache 17 0 25 0.8 Neuropathy peripheral 12 0.4 15 2 Paresthesia 10 0.8 8 0 Dizziness 13 0 11 0 Investigations Weight decreased 11 0.8 6 0.8 Musculoskeletal and connective tissue disorders Myalgia 25 0.4 19 0.4 Arthralgia 24 0 28 0.4 Back pain 10 0 4.8 0 Bone pain 7 0 5 0 Pain in extremity 6 0 8 0 Muscle spasms 6 0 7 0 Musculoskeletal pain 6 0.4 8 0 Respiratory, thoracic and mediastinal disorder Cough 15 0.4 13 0 Epistaxis 12 0 14 0.4 Dyspnea 10 1.2 5 0 Rhinorrhea 7 0 4.4 0 Infections and infestations Upper respiratory tract infection 11 0 8 0.8 Nasopharyngitis 9 0 10 0 Paronychia 7 0.4 3.6 0 Urinary tract infection 7 0.4 5 0 Injury, poisoning and procedural complications Procedural pain 13 0 10 0 Radiation skin injury 19 0.4 19 0.4 Infusion related reaction 3.6 0 15 0.8 Metabolism and nutrition disorders Decreased appetite 17 0.8 19 0.4 Hypokalemia 7 1.6 8 0 Psychiatric disorders Insomnia 17 0 13 0.4 Eye disorders Lacrimation increased 5 0.4 6 0 Dry eye 5 0.4 3.2 0 Vascular disorders Hot flush 12 0 13 0 Clinically relevant adverse reactions in <5% of patients who received PHESGO include ejection fraction decreased (3.6%) and pruritus (3.2%).
In the FeDeriCa trial, when PHESGO was administered alone, adverse reactions occurred in <10% of patients with the exception of radiation skin injury (20%), arthralgia (19%), diarrhea (17%), injection site reaction (13%), dyspepsia (12%), asthenia (11%), hot flush (11%), and pruritus (10%).
Table 4 summarizes the laboratory abnormalities in FeDeriCa.
Table 4: Select Laboratory Abnormalities (≥5%) that Worsened from Baseline in Patients Who Received PHESGO in FeDeriCa The denominator used to calculate the rate varied from 163 to 252 based on the number of patients with a baseline value and at least one post-treatment value.
Laboratory Abnormality PHESGO (n=248) Intravenous pertuzumab plus intravenous or subcutaneous trastuzumab (n=252) All Grades % Grades 3 – 4 % All Grades % Grades 3 – 4 % Hematology Hemoglobin (low) 90 2.8 92 4.4 Lymphocytes, Absolute (low) 89 37 88 36 Total Leukocyte Count (low) 82 25 78 25 Neutrophils, Total Absolute (low) 68 30 67 33 Platelet (low) 27 0 28 0.4 Chemistry Creatinine (high) 84 0 87 0.4 Alanine aminotransferase (high) 58 1.6 68 2.4 Aspartate aminotransferase (high) 50 0.8 58 0.8 Potassium (low) 17 5.2 17 2.8 Albumin (low) 16 0 20 0.4 Potassium (high) 13 1.2 9 0 Sodium (low) 13 0.4 10 1.6 Bilirubin (high) 9 0 9 0.4 Glucose (low) 9 0 9 0.4 Sodium (high) 7 0.8 10 0.8 Other Clinical Trials Experience The safety of the addition of intravenous pertuzumab to trastuzumab in combination with chemotherapy has been established in studies conducted in patients with HER2 overexpressing early breast cancer.
The following adverse reactions have been reported following administration of intravenous pertuzumab and trastuzumab: diarrhea, alopecia, nausea, fatigue, neutropenia, vomiting, peripheral neuropathy, constipation, anemia, asthenia, mucosal inflammation, myalgia, and thrombocytopenia.
Refer to the Prescribing Information for pertuzumab for more information.
The safety of intravenous pertuzumab, trastuzumab and docetaxel has been established in patients with HER2 overexpressing metastatic breast cancer.
The following adverse reactions have been reported following administration of intravenous pertuzumab and trastuzumab: diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy.
Refer to the Prescribing Information for pertuzumab for more information.
6.2 Postmarketing Experience The following adverse reactions have been identified with the use of intravenous trastuzumab.
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.
Glomerulopathy Immune thrombocytopenia Tumor lysis syndrome (TLS): 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.