4) ] Metastatic Breast Cancer The most common adverse reactions (> 30%) with PERJETA in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy. 1 ) Neoadjuvant Treatment of Breast Cancer The most common adverse reactions (> 30%) with PERJETA in combination with trastuzumab and docetaxel were alopecia, diarrhea, nausea, and neutropenia.
1 ) The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel when given for 3 cycles following 3 cycles of FEC were fatigue, alopecia, diarrhea, nausea, vomiting, and neutropenia. 1 ) The most common adverse reactions (>30%) with PERJETA in combination with docetaxel, carboplatin, and trastuzumab (TCH) were fatigue, alopecia, diarrhea, nausea, vomiting, neutropenia, thrombocytopenia, and anemia.
1 ) The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and paclitaxel when given for 4 cycles following 4 cycles of ddAC were nausea, diarrhea, alopecia, fatigue, constipation, peripheral neuropathy, and headache.
1 ) The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel when given for 4 cycles following 4 cycles of FEC were diarrhea, nausea, alopecia, asthenia, constipation, fatigue, mucosal inflammation, vomiting, myalgia, and anemia.
1 ) Adjuvant Treatment of Breast Cancer The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and chemotherapy were diarrhea, nausea, alopecia, fatigue, peripheral neuropathy and vomiting. gov/medwatch .
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 clinical practice.
1) ] . Patients received either PERJETA administered at an initial dose of 840 mg followed by 420 mg every 3 weeks thereafter or placebo in combination with trastuzumab (initial dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks thereafter) and docetaxel (75 mg/m2 by intravenous infusion every 3 weeks for 6 cycles).
1 months for patients in the PERJETA-treated group. Permanent discontinuation of PERJETA, trastuzumab, and docetaxel due to adverse reactions occurred in 6% of patients. Adverse reactions that led to permanent discontinuation of PERJETA, trastuzumab, and docetaxel in >1% of patients were left ventricular dysfunction.
75 years of follow-up (median total follow-up of 50 months) in CLEOPATRA. The most common adverse reactions (> 30%) with PERJETA in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy.
The most common 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 3 summarizes the adverse reactions in CLEOPATRA that occurred ≥ 10% of patients in the PERJETA-treated group.
3 Respiratory, thoracic, and mediastinal disorders Dyspnea 14 1 16 2 Eye disorders Lacrimation increased 14 0 14 0 Psychiatric disorders Insomnia 13 0 13 0 Clinically relevant adverse reactions in < 10% of patients in the PERJETA-treated group in CLEOPATRA included paronychia (7%).
Adverse Reactions Reported in Patients Receiving PERJETA and Trastuzumab After Discontinuation of Docetaxel In CLEOPATRA, adverse reactions that occurred after discontinuation of docetaxel included diarrhea (19%), upper respiratory tract infection (13%), rash (12%), headache (11%), and fatigue (11%).
2) ] . In combination with trastuzumab and docetaxel, PERJETA was given intravenously at an initial dose of 840 mg, followed by 420 mg every 3 weeks for 4 cycles. After surgery, patients in the PERJETA plus trastuzumab arm received docetaxel every 3 weeks for 4 cycles prior to FEC.
9% of patients. The most common adverse reactions (> 30%) were alopecia, neutropenia, diarrhea, and nausea. The most common Grade 3 – 4 adverse reactions (> 2%) were neutropenia, febrile neutropenia, leukopenia, and diarrhea. Table 4 summarizes the adverse reactions in NeoSphere that occurred ≥ 10% of patients who received neoadjuvant PERJETA with trastuzumab and docetaxel followed by FEC.
9 Headache 11 0 11 0 Dysgeusia 10 0 15 0 Psychiatric disorders Insomnia 11 0 8 0 Metabolism and nutrition disorders Decreased appetite 7 0 14 0 Clinically relevant adverse reactions in < 10% of patients receiving neoadjuvant PERJETA with trastuzumab and docetaxel followed by FEC included anemia, febrile neutropenia, dizziness, upper respiratory tract infection, and increased lacrimation.
2) ]. 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. For PERJETA 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 Grade 3 – 4 adverse reactions (> 2%) were neutropenia, leukopenia, febrile neutropenia, diarrhea, left ventricular dysfunction, anemia, dyspnea, nausea, and vomiting. For PERJETA 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 Grade 3 – 4 adverse reactions (> 2%) were neutropenia, febrile neutropenia, anemia, leukopenia, diarrhea, thrombocytopenia, vomiting, fatigue, ALT increased, hypokalemia, and hypersensitivity. Table 5 summarizes the adverse reactions in TRYPHAENA that occurred in > 10% of patients who received neoadjuvant PERJETA with trastuzumab and docetaxel following FEC or who received neoadjuvant PERJETA in combination with TCH.
Table 5:
Adverse Reactions (≥ 10%) in Patients Receiving Neoadjuvant Treatment with PERJETA in TRYPHAENA Adverse Reactions PERJETA + trastuzumab + docetaxel following FEC PERJETA + TCH n=75 % n=76 % All Grades % Grades 3 – 4 % All Grades % Grades 3 – 4 % Gastrointestinal disorders Diarrhea 61 5 72 12 Nausea 53 3 45 0 Vomiting 36 3 39 5 Dyspepsia 8 0 22 0 Constipation 23 0 16 0 Stomatitis 17 0 12 0 Skin and subcutaneous tissue disorders Alopecia 52 0 55 0 Rash 11 0 21 1 Palmar-Plantar Erythrodysaesthesia Syndrome 11 0 8 0 Dry skin 9 0 11 0 Blood and lymphatic system disorders Neutropenia 47 43 49 46 Leukopenia 16 12 17 12 Anemia 9 4 38 17 Febrile neutropenia 9 9 17 17 Thrombocytopenia 1 0 30 12 General disorders and administration site conditions Fatigue 36 0 42 4 Mucosal inflammation 20 0 17 1 Pyrexia 9 0 16 0 Asthenia 15 1 13 1 Edema peripheral 4 0 9 0 Psychiatric disorders Insomnia 13 0 21 0 Nervous system disorders Headache 15 0 17 0 Dysgeusia 13 0 21 0 Dizziness 8 1 16 0 Neuropathy peripheral 1 0 11 0 Metabolism and nutrition disorders Decreased appetite 11 0 21 0 Respiratory, thoracic, and mediastinal disorders Epistaxis 11 0 16 1 Dyspnea 8 3 11 1 Oropharyngeal pain 7 0 12 0 Cough 5 0 12 0 Musculoskeletal and connective tissue disorders Myalgia 11 1 11 0 Arthralgia 12 0 7 0 Eye disorders Lacrimation increased 5 0 8 0 Investigations ALT increased 3 0 11 4 Immune system disorders Hypersensitivity 1 0 12 3 Clinically relevant adverse reactions in < 10% of patients who received neoadjuvant PERJETA with trastuzumab and docetaxel following FEC or who received neoadjuvant PERJETA in combination with TCH included nail disorder, paronychia, pruritus, upper respiratory tract infection, and nasopharyngitis.
2) ]. 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 peripheral neuropathy, decreased ejection fraction, diarrhea, neutropenia and infusion-related reaction. For PERJETA 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, decreased neutrophil count, decreased white blood cell count, anemia, diarrhea, peripheral neuropathy, increased ALT, and nausea. For PERJETA 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, decreased neutrophil count stomatitis, fatigue, vomiting, mucosal inflammation, neutropenic sepsis and anemia. Table 6 summarizes the adverse reactions in BERENICE that occurred in ≥ 10% of patients who received neoadjuvant PERJETA with trastuzumab and paclitaxel following ddAC or who received neoadjuvant PERJETA with trastuzumab and docetaxel following FEC.
5 Metabolism and nutrition disorders Decreased appetite 20 0 23 0 Psychiatric disorders Insomnia 19 0 13 0 Vascular disorders Hot flush 19 0 13 0 Injury, poisoning and procedural complications Infusion-related reaction 16 1 13 1 Eye disorders Increased lacrimation 9 0 18 0 Investigations Decreased white blood cell count 11 4 3 2 Infections and infestations Urinary tract infection 11 1 2 0 Clinically relevant adverse reactions in < 10% of patients who received PERJETA in combination with trastuzumab and paclitaxel following ddAC or patients receiving PERJETA in combination with trastuzumab and docetaxel following FEC included pruritus, nail disorder, paronychia, upper respiratory tract infection, and nasopharyngitis.
3) ]. Patients were randomized to receive either PERJETA in combination with trastuzumab and chemotherapy or placebo in combination with trastuzumab and chemotherapy. Investigators selected one of three anthracycline-based or non-anthracycline-based chemotherapy regimens for patients.
PERJETA and trastuzumab were administered intravenously every 3 weeks starting on Day 1 of the first taxane-containing cycle, for a total of 52 weeks (up to 18 cycles) or until recurrence, withdrawal of consent, or unmanageable toxicity.
4%. The incidence of diarrhea was higher when chemotherapy was administered with PERJETA (61%) and was higher when administered with non-anthracycline based therapy (85%) than with anthracycline based therapy (67%). The median duration of diarrhea was 8 days.
The median duration of Grade ≥3 diarrhea was 20 days. The incidence of diarrhea during the period PERJETA and trastuzumab were administered without chemotherapy was 18% in the PERJETA-treated group. Adverse reactions resulting in permanent discontinuation of any study therapy were 13% for patients in the PERJETA-treated group.
Adverse reactions resulting in permanent discontinuation of PERJETA was 7%. 5%) resulting in permanent discontinuation of any study treatment were ejection fraction decreased, neuropathy peripheral, diarrhea, and cardiac failure. 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. Table 7 summarizes the adverse reactions that occurred in ≥ 10% of patients who received adjuvant PERJETA in combination with trastuzumab and chemotherapy followed by PERJETA and trastuzumab for a total of 52 weeks (up to 18 cycles) or until recurrence, withdrawal of consent, or unmanageable toxicity.
3 Clinically relevant adverse reactions in < 10% of patients who received PERJETA in combination with trastuzumab and anthracycline-based or non-anthracycline-based chemotherapy regimens included l eukopenia, upper respiratory tract infection, and paronychia Adverse Reactions in Patients Receiving PERJETA and Trastuzumab After Discontinuation of Chemotherapy In APHINITY, adverse reactions that occurred after discontinuation of chemotherapy in >10% included diarrhea (18%), arthralgia (15%), radiation skin injury (12%), and hot flush (12%).