Does Perjeta (pertuzumab) cause side effects?
Perjeta (pertuzumab) is a monoclonal antibody used to treatbreast cancerthat has spread beyond the breast (metastasized).
The cells ofcancershave various receptors on their surfaces. Chemicals bind to these receptors and cause changes within thecancercells. One of the receptors that occurs in about one-third of all breast cancers is called HER2, which is known to control the growth and development of thecancercells and the production of newcancercells.
If HER2 receptors are present in large numbers on the cancer cells, then the cancer cells may multiply and grow quickly. Normally, the immune system produces antibodies that will detect and attack HER2 receptors to slow the growth of cancer cells.
However, if HER2 is present in large amounts, the immune system may be unable to control HER2. Perjeta is thought to block the HER2 receptors when there is overexpression, thereby blocking growth of the cancer.
Common side effects of Perjeta include
- diarrhea,
- nausea,
- vomiting,
- anemia,
- inflammation of the mouth and lips,
- reduced number of white blood cells,
- inflammation ofmucusmembranes in the digestive tract,
- rash,
- hair loss,
- weakness,
- itching,
- painin extremities, and
- changes in sense of taste.
Serious side effects of Perjeta include
- heart failure,
- infusion reactions,
- seriousallergicreactions,
- reducedred blood cells(anemia),
- reduced platelets, and
- reduced white blood cells (which increases the risk for febrileneutropeniaand infections).
The manufacturer has not identified any Perjetadrug interactions.
Perjeta can cause fetal harm when administered topregnant女人,要d not be administered duringpregnancy.
It is unknown if Perjeta is excreted inhuman milk.Breastfeedingmothers should decide whether to stopnursingor discontinue Perjeta.
What are the important side effects of Perjeta (pertuzumab)?
Common side effects of pertuzumab include:
- Diarrhea
- Nausea
- Vomiting
- Anemia
- Stomatitis
- Reduced number of white blood cells
- Mucositis
- Rash
- Hair loss
- Weakness
- Itching
- Painin extremities
- Changes in sense of taste (dysgeusia)
Pertuzumab also causesheartfailure, infusion reactions, and serious allergic reactions. Treatment may also reduce the number of red blood cells (anemia), and reduce the number of platelets and white blood cells. A reduced number of white blood cells increases the risk for febrile neutropenia and infections.
Perjeta (pertuzumab) side effects list for healthcare professionals
The following adverse reactions are discussed in greater detail in other sections of the label:
- Left Ventricular Dysfunction
- Embryo-Fetal Toxicity
- Infusion-Related Reactions
- Hypersensitivity Reactions/Anaphylaxis
Clinical Trials Experience
Becauseclinical trialsare 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 metastaticbreast cancertreated in CLEOPATRA. Patients were randomized to receive either Perjeta in combination withtrastuzumabanddocetaxelor 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.
不良反应导致永久性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 % |
成绩3 – 4 % |
All Grades % |
成绩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)
在NeoSphere,最常见的不良反应en 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 forbreast cancerin 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 % |
成绩3 – 4 % | All Grades % |
成绩3 – 4 % |
All Grades % |
成绩3 – 4 % |
All Grades % |
成绩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.
不良反应导致永久性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 % |
成绩3 – 4 % |
All Grades % |
成绩3 – 4 % |
All Grades % |
成绩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, andcyclophosphamide; 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)
乳腺癌的新辅助治疗(贝蕾妮斯)
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,
- 粘膜炎症,
- vomiting,
- myalgia, and
- anemia.
The most common Grade 3 – 4 adverse reactions (> 2%) were
- febrile neutropenia,
- diarrhea,
- neutropenia,
- neutrophil count decreased,
- stomatitis,
- fatigue,
- vomiting,
- 粘膜炎症,
- neutropenicsepsisand
- anemia.
不良反应导致永久性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 % |
成绩 3 – 4 % |
All Grades % |
成绩 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 andchemotherapyor placebo in combination with trastuzumab and chemotherapy.
不良反应导致永久性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.
腹泻的发病率,所有成绩,是更高的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 % |
成绩 3 – 4 % |
All Grades % |
成绩 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 |
的不良反应报道≥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+ACchemoarm, 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%),
- radiationskin injury (12%), and
- hotflush(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.
- Tumorlysis 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 withhyperuricemia, hyperphosphatemia, andacute renal failurewhich may represent possible TLS. Providers should consider additional monitoring and/or treatment as clinically indicated.
Summary
Perjeta (pertuzumab) is a monoclonal antibody used to treat breast cancer that has spread beyond the breast (metastasized). Common side effects of Perjeta include diarrhea, nausea, vomiting, anemia, inflammation of the mouth and lips, reduced number of white blood cells, inflammation of mucus membranes in the digestive tract, rash, hair loss, weakness, itching, pain in extremities, and changes in sense of taste. Perjeta can cause fetal harm when administered to pregnant women and should not be administered during pregnancy. It is unknown if Perjeta is excreted in human milk.
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Breast Cancer in Men
Second Source WebMD Medical Reference
Male Breast Cancer
Male breast cancer accounts for 1% of all breast cancers, and most cases are found in men between the ages of 60 and 70. A man's risk of developing breast cancer is one in 1,000. Signs and symptoms include a firm mass located below the nipple and skin changes around the nipple, including puckering, redness or scaling, retraction and ulceration of the nipple. Treatment depends upon staging and the health of the patient.
Breast Cancer
乳腺癌是一种侵入性肿瘤发展n the mammary gland. Breast cancer is detected via mammograms, breast self-examination (BSE), biopsy, and specialized testing on breast cancer tissue. Treatment of breast cancer may involve surgery, radiation, hormone therapy, chemotherapy, and targeted therapy. Breast cancer risk may be lowered by managing controllable risk factors. What you should know about breast cancer Breast cancer is the most common cancer among American women. One in every eight women in the United States develops breast cancer. There are many types of breast cancer that differ in their capability of spreading (metastasize) to other body tissues. The causes of breast cancer are unknown, although medical professionals have identified a number of risk factors. There are 11 common types of breast cancer and 4 uncommon types of breast cancer. Breast cancer early signs and symptoms include a lump in the breast or armpit, bloody nipple discharge, inverted nipple, orange-peel texture or dimpling of the breast's skin (peau d'orange), breast pain or sore nipple, swollen lymph nodes in the neck or armpit, and a change in the size or shape of the breast or nipple. Breast cancer can also be symptom free, which makes following national screening recommendations an important practice. Breast cancer is diagnosed during a physical exam, by a self-exam of the breasts, mammography, ultrasound testing, and biopsy. Treatment of breast cancer depends on the type of cancer and its stage (0-IV) and may involve surgery, radiation, or chemotherapy.
Triple-Negative Breast Cancer
Triple-negative breast cancer is more common in Hispanic and African-American women. Signs and symptoms include a lump in the armpit or breast, nipple discharge and inversion, and changes in the breast's skin. Treatment may incorporate surgery, chemotherapy, and radiation therapy.
Can Fibroadenomas Turn Into Breast Cancer?
A fibroadenoma is the most common type of benign, non-cancerous lump of the breast. Although it is rare, complex fibroadenomas and phyllodes tumors have a chance to develop into malignant breast cancer.
Inflammatory Breast Cancer
Inflammatory breast cancer is an accelerated form of breast cancer that is not usually detected by mammogram or ultrasound. Symptoms of inflammatory breast cancer include pain in the breast, skin change in the breast area, bruise on the breast,sudden swelling of the breast, nipple retraction or discharge, and swelling of the lymph nodes.
Breast Cancer Prevention
Lifestyle changes, a healthy antioxidant-rich diet, exercise, and weight reduction can help reduce a woman's risk of developing breast cancer. It's important to be aware of how risk factors such as family history, lifestyle factors, breast conditions, radiation therapy, and hormonal factors may influence your chances of developing breast cancer. Mammography and breast self-examinations are crucial steps in breast cancer prevention.
Breast Cancer and Coping With Stress
Being diagnosed with breast cancer is stressful. Learning relaxation techniques, exercising, eating well, getting adequate sleep, receiving psychotherapy, and maintaining a positive attitude can help you cope. Creating documents, such as an advance directive, living will, and durable power of attorney will outline your wishes in the event that you are no longer able to make decisions regarding your care.
Breast Cancer and Lymphedema
Lymphedema is a common chronic, debilitating condition in which excess fluid called lymph collects in tissues and causes swelling in them. It is common after a mastectomy, lumpectomy or breast cancer surgery and radiation therapy.
Breast Cancer Recurrence
Breast cancer most often recurs within the first 3-5 years after the initial treatment. Changes in the look, feel, or appearance of the breast may indicate breast cancer recurrence. Factors related to recurrence include tumor size, tumor grade, hormone receptor status, lymph node involvement, and oncogene expression. Check out the center below for more medical references on breast cancer, including multimedia (slideshows, images, and quizzes), related diseases, treatment, diagnosis, medications, and prevention or wellness.
Breast Cancer Stages
Breast cancer staging is the determination of the extent and spread of cancer. An individual's health care team uses stages to summarize the extent of cancer in a standardized way that is recognized by all health care providers. They use this staging to determine the treatment most appropriate for the type of cancer. Cancer staging helps to determine the prognosis, or outlook, of cancer, including rates of recurrence and survival rates.
HER2-Positive Breast Cancer
In about 10%-20% of breast cancers, the cancer cells test positive for HER2, sometimes referred to as the HER2/neu protein. HER2 is a growth-promoting protein located on the surface of some cancer cells. HER2-positive breast cancers tend to grow more rapidly and spread more aggressively than breast cancers that are HER2-negative. Doctors do not know what specifically causes some breast cancers to express this protein while others do not.
Breast Cancer Early Warning Signs and Symptoms
In most cases, there are no early warning signs of breast cancer. Breast cancer may not produce any early symptoms, and in many cases, it is first discovered on screening mammography. The most common sign of breast cancer is a new lump or mass in the breast.
Breast Cancer Treatment
Breast cancer treatments depend upon the type of breast cancer that is present as well as the stage (extent of spread) of the tumor. Treatment for early breast cancer typically involves surgery to remove the tumor. After surgery, medical professionals may administer radiation therapy, chemotherapy, or targeted therapy.
What Is the Breast Cancer BRCA Gene Test?
BRCA genes (BRCA 1 and 2, when normal, repair damaged DNA) are among the genetic mutations linked to breast cancer, ovarian cancer, and other cancers when mutated. Every woman with a BRCA mutation is at high risk for breast cancer, irrespective of whether she has a family history of breast cancer or not. By age 80, a woman with a BRCA mutation has about an 80% chance of developing breast cancer. BRCA1 and BRCA2 gene mutations also increase the risk of ovarian cancer, by 54% and 23%, respectively.
What Questions Should I Ask My Doctor About Breast Cancer?
A diagnosis of breast cancer can be overwhelming, so it's important to write down all your questions before meeting with your doctor.
What Should I Know About Breast Cancer?
Breast cancer is the most common non-skin cancer of American women, but it can also occur in men. Every year in the U.S., there are over 266,000 new diagnoses of breast cancer. A woman has a risk of one in eight for developing breast cancer at some point during her lifetime.
Breast Cancer Treatment by Stage
Treatment of breast cancer depends upon the stage of the cancer at the time of diagnosis. Some of the various treatments include: hormone therapy, radiation therapy, surgery, chemotherapy, HER2-targeted therapy, neoadjuvant therapy, and adjuvant therapy.
Breast Cancer in Young Women
About 5% of cases of breast cancer occur in women under the age of 40 years old. Some risk factors for breast cancer in young women include a personal history of breast cancer or breast disease, family history of breast cancer, prior radiation therapy, and the presence of BRCA1/BRCA2 gene mutations. Breast self-exams, clinical breast exams, and screening mammograms may help detect breast cancer. Treatment may include surgery, chemotherapy, radiation, and hormone therapy.
Breast Cancer Clinical Trials
乳腺癌的临床试验研究项目s designed to evaluate new medical treatments, drugs, or devices for the treatment of breast cancer. Clinical trials are designed to test the safety and efficacy of new treatments as well as assess potential side effects. Clinical trials also compare new treatment to existing treatments to determine if it's any better. There are many important questions to ask your doctor before taking part in a breast cancer clinical trial.
Breast Cancer During Pregnancy
Breast cancer occurs in about 1 in every 1,000 pregnant women. Treatment of breast cancer during pregnancy involves surgery, but it is very difficult to protect the baby from the dangerous effects of radiation and chemotherapy. It can be an agonizing to decide whether or not to undergo breast cancer treatment while one is pregnant.
Genetic Testing: Families With Breast Cancer
Breast cancer can be a killer and the decision to get tested to see if a patient is prone to the disease should be discussed with a doctor -- particularly if the woman has a history of breast cancer in her family. Genetic testing can only tell so much about breast cancer risk, however.
Treatment & Diagnosis
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- Breast Cancer, Metastatic: Treatment Goals and Therapy Options -- Harold J. Burstein, MD
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