Medical Editor: John P. Cunha, DO, FACOEP
What Is Herceptin?
Herceptin (trastuzumab) is a cancer medicine used to treat breast cancer that has progressed after treatment with other chemotherapy.
What Are Side Effects of Herceptin?
Common side effects of Herceptin include:
- diarrhea,
- redness or irritation at injection (IV) site,
- muscle/joint/back pain,
- stomach or abdominal pain,
- headache,
- sleep problems (insomnia),
- nausea and vomiting (may be severe),
- weight loss,
- rash,
- altered sense of taste,
- mouth sores,
- loss of appetite,
- tiredness, and
- cold symptoms such as stuffy nose, sinus pain, sneezing, or sore throat.
Tell your doctor if you have serious side effects of Herceptin including:
- bone pain,
- increased coughing,
- swelling of the hands/ankles/feet,
- sudden unexplained weight gain,
- unusual tiredness,
- severe headache,
- tingling or numbness (e.g., in the hands, feet, leg),
- mental/mood changes,
- fast or pounding heartbeat, and
- easy bruising or bleeding.
Dosage for Herceptin
Dose of Herceptin depends on the type of cancer being treated, and whether other chemotherapy drugs are being given, among other factors.
What Drugs, Substances, or Supplements Interact with Herceptin?
Other drugs may affect Herceptin. Tell your doctor all prescription and over-the-counter medications and supplements you use.
Herceptin During Pregnancy and Breastfeeding
Herceptin is not recommended during pregnancy because of the possible risk of harm to a fetus. This drug should only be used during pregnancy if the benefits outweigh these risks. Use 2 forms of birth control (e.g., condoms and birth control pills/patch/ring) while using this medication and for 6 month after treatment has stopped. Consult your doctor for details and to discuss birth control. It is not known whether this drug passes into breast milk. Because of the possible risk to the infant, breastfeeding is not recommended while using this drug or for 6 months after the last dose.
Additional Information
Our Herceptin (trastuzumab) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
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.

QUESTION
A lump in the breast is almost always cancer. See AnswerGet 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, or in the days afterward. Tell your caregiver right away if you feel dizzy, nauseated, itchy, light-headed, weak, short of breath, or if you have a headache, fever, chills, or chest pain.
Call your doctor at once if you have:
- new or worsening cough;
- a light-headed feeling, like you might pass out;
- severe headache, blurred vision, pounding in your neck or ears;
- blisters or ulcers in your mouth, red or swollen gums, trouble swallowing;
- heart problems--pounding heartbeats, dizziness, swelling in your lower legs, rapid weight gain, feeling short of breath;
- low blood cell counts--fever, chills, tiredness, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed; or
- signs of tumor cell breakdown--tiredness, weakness, muscle cramps, nausea, vomiting, diarrhea, fast or slow heart rate, 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 may include:
- heart problems;
- nausea, diarrhea, weight loss;
- headache;
- trouble sleeping, feeling tired;
- low blood cell counts;
- rash;
- fever, chills, cough, or other signs of infection;
- mouth sores;
- altered sense of taste; or
- cold symptoms such as stuffy nose, sinus pain, sore throat.
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 Herceptin (Trastuzumab)

SLIDESHOW
Breast Cancer Awareness: Symptoms, Diagnosis, and Treatment See SlideshowSIDE EFFECTS
The following adverse reactions are discussed in greater detail in other sections of the label:
- Cardiomyopathy [see WARNINGS AND PRECAUTIONS]
- Infusion Reactions [see WARNINGS AND PRECAUTIONS]
- Embryo-Fetal Toxicity [see WARNINGS AND PRECAUTIONS]
- Pulmonary Toxicity [see WARNINGS AND PRECAUTIONS]
- Exacerbation of Chemotherapy-Induced Neutropenia [see WARNINGS AND PRECAUTIONS]
The most common adverse reactions in patients receiving Herceptin in the adjuvant and metastatic breast cancer setting are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia. Adverse reactions requiring interruption or discontinuation of Herceptin treatment include CHF, significant decline in left ventricular cardiac function, severe infusion reactions, and pulmonary toxicity [see DOSAGE AND ADMINISTRATION].
In the metastatic gastric cancer setting, the most common adverse reactions (≥ 10%) that were increased (≥ 5% difference) in the Herceptin arm as compared to the chemotherapy alone arm were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia. The most common adverse reactions which resulted in discontinuation of treatment on the Herceptincontaining arm in the absence of disease progression were infection, diarrhea, and febrile neutropenia.
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.
Adjuvant Breast Cancer Studies
The data below reflect exposure to one-year Herceptin therapy across three randomized, open-label studies, Studies 1, 2, and 3, with (n = 3678) or without (n = 3363) trastuzumab in the adjuvant treatment of breast cancer.
The data summarized in Table 3 below, from Study 3, reflect exposure to Herceptin in 1678 patients; the median treatment duration was 51 weeks and median number of infusions was 18. Among the 3386 patients enrolled in the observation and one-year Herceptin arms of Study 3 at a median duration of follow-up of 12.6 months in the Herceptin arm, the median age was 49 years (range: 21 to 80 years), 83% of patients were Caucasian, and 13% were Asian.
Table 3 : Adverse Reactions for Study 3a,
All Gradesb
Adverse Reaction | One Year Herceptin (n = 1678) |
Observation (n = 1708) |
Cardiac | ||
Hypertension | 64 (4%) | 35 (2%) |
Dizziness | 60 (4%) | 29 (2%) |
Ejection Fraction Decreased | 58 (3.5%) | 11 (0.6%) |
Palpitations | 48 (3%) | 12 (0.7%) |
Cardiac Arrhythmiasc | 40 (3%) | 17 (1%) |
Cardiac Failure Congestive | 30 (2%) | 5 (0.3%) |
Cardiac Failure | 9 (0.5%) | 4 (0.2%) |
Cardiac Disorder | 5 (0.3%) | 0 (0%) |
Ventricular Dysfunction | 4 (0.2%) | 0 (0%) |
Respiratory Thoracic Mediastinal Disorders | ||
Cough | 81 (5%) | 34 (2%) |
Influenza | 70 (4%) | 9 (0.5%) |
Dyspnea | 57 (3%) | 26 (2%) |
URI | 46 (3%) | 20 (1%) |
Rhinitis | 36 (2%) | 6 (0.4%) |
Pharyngolaryngeal Pain | 32 (2%) | 8 (0.5%) |
Sinusitis | 26 (2%) | 5 (0.3%) |
Epistaxis | 25 (2%) | 1 (0.06%) |
Pulmonary Hypertension | 4 (0.2%) | 0 (0%) |
Interstitial Pneumonitis | 4 (0.2%) | 0 (0%) |
Gastrointestinal Disorders | ||
Diarrhea | 123 (7%) | 16 (1%) |
Nausea | 108 (6%) | 19 (1%) |
Vomiting | 58 (3.5%) | 10 (0.6%) |
Constipation | 33 (2%) | 17 (1%) |
Dyspepsia | 30 (2%) | 9 (0.5%) |
Upper Abdominal Pain | 29 (2%) | 15 (1%) |
Musculoskeletal & Connective Tissue Disorders | ||
Arthralgia | 137 (8%) | 98 (6%) |
Back Pain | 91 (5%) | 58 (3%) |
Myalgia | 63 (4%) | 17 (1%) |
Bone Pain | 49 (3%) | 26 (2%) |
Muscle Spasm | 46 (3%) | 3 (0.2%) |
Nervous System Disorders | ||
Headache | 162 (10%) | 49 (3%) |
Paraesthesia | 29 (2%) | 11 (0.6%) |
Skin & Subcutaneous Tissue Disorders | ||
Rash | 70 (4%) | 10 (0.6%) |
Nail Disorders | 43 (2%) | 0 (0%) |
Pruritus | 40 (2%) | 10 (0.6%) |
General Disorders | ||
Pyrexia | 100 (6%) | 6 (0.4%) |
Edema Peripheral | 79 (5%) | 37 (2%) |
Chills | 85 (5%) | 0 (0%) |
Asthenia | 75 (4.5%) | 30 (2%) |
Influenza-like Illness | 40 (2%) | 3 (0.2%) |
Sudden Death | 1 (0.06%) | 0 (0%) |
Infections | ||
Nasopharyngitis | 135 (8%) | 43 (3%) |
UTI | 39 (3%) | 13 (0.8%) |
Immune System Disorders | ||
Hypersensitivity | 10 (0.6%) | 1 (0.06%) |
Autoimmune Thyroiditis | 4 (0.3%) | 0 (0%) |
a Median follow-up duration of 12.6 months in
the one-year Herceptin treatment arm. b The incidence of Grade 3 or higher adverse reactions was <1% in both arms for each listed term. c Higher level grouping term. |
In Study 3, a comparison of 3-weekly Herceptin treatment for two years versus one year was also performed. The rate of asymptomatic cardiac dysfunction was increased in the 2-year Herceptin treatment arm (8.1% versus 4.6% in the one-year Herceptin treatment arm). More patients experienced at least one adverse reaction of Grade 3 or higher in the 2-year Herceptin treatment arm (20.4%) compared with the one-year Herceptin treatment arm (16.3%).
The safety data from Studies 1 and 2 were obtained from 3655 patients, of whom 2000 received Herceptin; the median treatment duration was 51 weeks. The median age was 49 years (range: 24-80); 84% of patients were White, 7% Black, 4% Hispanic, and 3% Asian.
In Study 1, only Grade 3-5 adverse events, treatment-related Grade 2 events, and Grade 2-5 dyspnea were collected during and for up to 3 months following protocol-specified treatment. The following non-cardiac adverse reactions of Grade 2-5 occurred at an incidence of at least 2% greater among patients receiving Herceptin plus chemotherapy as compared to chemotherapy alone: fatigue (29.5% vs. 22.4%), infection (24.0% vs. 12.8%), hot flashes (17.1% vs. 15.0%), anemia (12.3% vs. 6.7%), dyspnea (11.8% vs. 4.6%), rash/desquamation (10.9% vs. 7.6%), leukopenia (10.5% vs. 8.4%), neutropenia (6.4% vs. 4.3%), headache (6.2% vs. 3.8%), pain (5.5% vs. 3.0%), edema (4.7% vs. 2.7%), and insomnia (4.3% vs. 1.5%). The majority of these events were Grade 2 in severity.
In Study 2, data collection was limited to the following investigator-attributed treatment-related adverse reactions: NCI-CTC Grade 4 and 5 hematologic toxicities, Grade 3-5 non-hematologic toxicities, selected Grade 2-5 toxicities associated with taxanes (myalgia, arthralgias, nail changes, motor neuropathy, and sensory neuropathy) and Grade 1-5 cardiac toxicities occurring during chemotherapy and/or Herceptin treatment. The following non-cardiac adverse reactions of Grade 2-5 occurred at an incidence of at least 2% greater among patients receiving Herceptin plus chemotherapy as compared to chemotherapy alone: arthralgia (12.2% vs. 9.1%), nail changes (11.5% vs. 6.8%), dyspnea (2.4% vs. 0.2%), and diarrhea (2.2% vs. 0%). The majority of these events were Grade 2 in severity.
Safety data from Study 4 reflect exposure to Herceptin as part of an adjuvant treatment regimen from 2124 patients receiving at least one dose of study treatment [AC-TH: n = 1068; TCH: n=1056].
The overall median treatment duration was 54 weeks in both the AC-TH and TCH arms. The median number of infusions was 26 in the AC-TH arm and 30 in the TCH arm, including weekly infusions during the chemotherapy phase and every three week dosing in the monotherapy period. Among these patients, the median age was 49 years (range 22 to 74 years). In Study 4, the toxicity profile was similar to that reported in Studies 1, 2, and 3 with the exception of a low incidence of CHF in the TCH arm.
Metastatic Breast Cancer Studies
The data below reflect exposure to Herceptin in one randomized, open-label study, Study 5, of chemotherapy with (n = 235) or without (n = 234) trastuzumab in patients with metastatic breast cancer, and one single-arm study (Study 6; n = 222) in patients with metastatic breast cancer. Data in Table 4 are based on Studies 5 and 6.
Among the 464 patients treated in Study 5, the median age was 52 years (range: 25-77 years). Eighty-nine percent were White, 5% Black, 1% Asian, and 5% other racial/ethnic groups. All patients received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly. The percentages of patients who received Herceptin treatment for ≥ 6 months and ≥ 12 months were 58% and 9%, respectively.
Among the 352 patients treated in single agent studies (213 patients from Study 6), the median age was 50 years (range 28-86 years), 86% were White, 3% were Black, 3% were Asian, and 8% in other racial/ethnic groups. Most of the patients received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly. The percentages of patients who received Herceptin treatment for ≥ 6 months and ≥ 12 months were 31% and 16%, respectively.
Table 4 : Per-Patient Incidence of Adverse Reactions
Occurring in ≥ 5% of Patients in Uncontrolled Studies or at Increased
Incidence in the Herceptin Arm (Studies 5 and 6)
Single Agenta n = 352 |
Herceptin + Paclitaxel n = 91 |
Paclitaxel Alone n = 95 |
Herceptin + ACb n = 143 |
ACb Alone n = 135 |
|
Body as a Whole | |||||
Pain | 47% | 61% | 62% | 57% | 42% |
Asthenia | 42% | 62% | 57% | 54% | 55% |
Fever | 36% | 49% | 23% | 56% | 34% |
Chills | 32% | 41% | 4% | 35% | 11% |
Headache | 26% | 36% | 28% | 44% | 31% |
Abdominal pain | 22% | 34% | 22% | 23% | 18% |
Back pain | 22% | 34% | 30% | 27% | 15% |
Infection | 20% | 47% | 27% | 47% | 31% |
Flu syndrome | 10% | 12% | 5% | 12% | 6% |
Accidental injury | 6% | 13% | 3% | 9% | 4% |
Allergic reaction | 3% | 8% | 2% | 4% | 2% |
Cardiovascular | |||||
Tachycardia | 5% | 12% | 4% | 10% | 5% |
Congestive heart failure | 7% | 11% | 1% | 28% | 7% |
Digestive | |||||
Nausea | 33% | 51% | 9% | 76% | 77% |
Diarrhea | 25% | 45% | 29% | 45% | 26% |
Vomiting | 23% | 37% | 28% | 53% | 49% |
Nausea and vomiting | 8% | 14% | 11% | 18% | 9% |
Anorexia | 14% | 24% | 16% | 31% | 26% |
Heme & Lymphatic | |||||
Anemia | 4% | 14% | 9% | 36% | 26% |
Leukopenia | 3% | 24% | 17% | 52% | 34% |
Metabolic | |||||
Peripheral edema | 10% | 22% | 20% | 20% | 17% |
Edema | 8% | 10% | 8% | 11% | 5% |
Musculoskeletal | |||||
Bone pain | 7% | 24% | 18% | 7% | 7% |
Arthralgia | 6% | 37% | 21% | 8% | 9% |
Nervous | |||||
Insomnia | 14% | 25% | 13% | 29% | 15% |
Dizziness | 13% | 22% | 24% | 24% | 18% |
Paresthesia | 9% | 48% | 39% | 17% | 11% |
Depression | 6% | 12% | 13% | 20% | 12% |
Peripheral neuritis | 2% | 23% | 16% | 2% | 2% |
Neuropathy | 1% | 13% | 5% | 4% | 4% |
Respiratory | |||||
Cough increased | 26% | 41% | 22% | 43% | 29% |
Dyspnea | 22% | 27% | 26% | 42% | 25% |
Rhinitis | 14% | 22% | 5% | 22% | 16% |
Pharyngitis | 12% | 22% | 14% | 30% | 18% |
Sinusitis | 9% | 21% | 7% | 13% | 6% |
Skin | |||||
Rash | 18% | 38% | 18% | 27% | 17% |
Herpes simplex | 2% | 12% | 3% | 7% | 9% |
Acne | 2% | 11% | 3% | 3% | < 1% |
Urogenital | |||||
Urinary tract infection | 5% | 18% | 14% | 13% | 7% |
a Data for Herceptin single agent were from 4
studies, including 213 patients from Study 6. b Anthracycline (doxorubicin or epirubicin) and cyclophosphamide. |
Metastatic Gastric Cancer
The data below are based on the exposure of 294 patients to Herceptin in combination with a fluoropyrimidine (capecitabine or 5-FU) and cisplatin (Study 7). In the Herceptin plus chemotherapy arm, the initial dose of Herceptin 8 mg/kg was administered on Day 1 (prior to chemotherapy) followed by 6 mg/kg every 21 days until disease progression. Cisplatin was administered at 80 mg/m² on Day 1 and the fluoropyrimidine was administered as either capecitabine 1000 mg/m² orally twice a day on Days 1-14 or 5-fluorouracil 800 mg/m²/day as a continuous intravenous infusion Days 1 through 5. Chemotherapy was administered for six 21-day cycles. Median duration of Herceptin treatment was 21 weeks; median number of Herceptin infusions administered was eight.
Table 5 : Study 7: Per Patient Incidence of Adverse
Reactions of All Grades (Incidence ≥ 5% between Arms) or Grade 3/4
(Incidence > 1% between Arms) and Higher Incidence in Herceptin Arm
Body System/Adverse Event | Herceptin + FC (N = 294) N (%) |
FC (N = 290) N (%) |
||
All Grades | Grades 3/4 | All Grades | Grades 3/4 | |
Investigations | ||||
Neutropenia | 230 (78) | 101 (34) | 212 (73) | 83 (29) |
Hypokalemia | 83 (28) | 28 (10) | 69 (24) | 16 (6) |
Anemia | 81 (28) | 36 (12) | 61 (21) | 30 (10) |
Thrombocytopenia | 47 (16) | 14 (5) | 33 (11) | 8 (3) |
Blood and Lymphatic System Disorders | ||||
Febrile Neutropenia | — | 15 (5) | — | 8 (3) |
Gastrointestinal Disorders | ||||
Diarrhea | 109 (37) | 27 (9) | 80 (28) | 11 (4) |
Stomatitis | 72 (24) | 2 (1) | 43 (15) | 6 (2) |
Dysphagia | 19 (6) | 7 (2) | 10 (3) | 1 (< 1) |
Body as a Whole | ||||
Fatigue | 102 (35) | 12 (4) | 82 (28) | 7 (2) |
Fever | 54 (18) | 3 (1) | 36 (12) | 0 (0) |
Mucosal Inflammation | 37 (13) | 6 (2) | 18 (6) | 2 (1) |
Chills | 23 (8) | 1 (< 1) | 0 (0) | 0 (0) |
Metabolism and Nutrition Disorders | ||||
Weight Decrease | 69 (23) | 6 (2) | 40 (14) | 7 (2) |
Infections and Infestations | ||||
Upper Respiratory Tract Infections | 56 (19) | 0 (0) | 29 (10) | 0 (0) |
Nasopharyngitis | 37 (13) | 0 (0) | 17 (6) | 0 (0) |
Renal and Urinary Disorders | ||||
Renal Failure and Impairment | 53 (18) | 8 (3) | 42 (15) | 5 (2) |
Nervous System Disorders | ||||
Dysgeusia | 28 (10) | 0 (0) | 14 (5) | 0 (0) |
The following subsections provide additional detail regarding adverse reactions observed in clinical trials of adjuvant breast cancer, metastatic breast cancer, metastatic gastric cancer, or post-marketing experience.
Cardiomyopathy
Serial measurement of cardiac function (LVEF) was obtained in clinical trials in the adjuvant treatment of breast cancer. In Study 3, the median duration of follow-up was 12.6 months (12.4 months in the observation arm; 12.6 months in the 1-year Herceptin arm); and in Studies 1 and 2, 7.9 years in the AC-T arm, 8.3 years in the AC-TH arm. In Studies 1 and 2, 6% of all randomized patients with post-AC LVEF evaluation were not permitted to initiate Herceptin following completion of AC chemotherapy due to cardiac dysfunction (LVEF < LLN or ≥ 16 point decline in LVEF from baseline to end of AC). Following initiation of Herceptin therapy, the incidence of new-onset dose-limiting myocardial dysfunction was higher among patients receiving Herceptin and paclitaxel as compared to those receiving paclitaxel alone in Studies 1 and 2, and in patients receiving one-year Herceptin monotherapy compared to observation in Study 3 (see Table 6, Figures 1 and 2). The per-patient incidence of new-onset cardiac dysfunction, as measured by LVEF, remained similar when compared to the analysis performed at a median follow-up of 2.0 years in the AC-TH arm. This analysis also showed evidence of reversibility of left ventricular dysfunction, with 64.5% of patients who experienced symptomatic CHF in the AC-TH group being asymptomatic at latest follow-up, and 90.3% having full or partial LVEF recovery.
Table 6a : Per-patient Incidence of New
Onset Myocardial Dysfunction (by LVEF) Studies 1, 2, 3 and 4
LVEF < 50% and Absolute Decrease from Baseline | Absolute LVEF Decrease | ||||
LVEF < 50% | ≥ 10% decrease | ≥ 16% decrease | < 20% and ≥ 10% | ≥ 20% | |
Studies 1 & 2bc | |||||
AC→TH | 23.1% | 18.5% | 11.2% | 37.9% | 8.9% |
(n = 1856) | (428) | (344) | (208) | (703) | (166) |
AC→T | 11.7% | 7.0% | 3.0% | 22.1% | 3.4% |
(n = 1170) | (137) | (82) | (35) | (259) | (40) |
Study 3d | |||||
Herceptin | 8.6% | 7.0% | 3.8% | 22.4% | 3.5% |
(n = 1678) | (144) | (118) | (64) | (376) | (59) |
Observation | 2.7% | 2.0% | 1.2% | 11.9% | 1.2% |
(n = 1708) | (46) | (35) | (20) | (204) | (21) |
Study 4e | |||||
TCH | 8.5% | 5.9% | 3.3% | 34.5% | 6.3% |
(n = 1056) | (90) | (62) | (35) | (364) | (67) |
AC→TH | 17% | 13.3% | 9.8% | 44.3% | 13.2% |
(n = 1068) | (182) | (142) | (105) | (473) | (141) |
AC→T | 9.5% | 6.6% | 3.3% | 34% | 5.5% |
(n = 1050) | (100) | (69) | (35) | (357) | (58) |
a For Studies 1, 2 and 3, events are counted
from the beginning of Herceptin treatment. For Study 4, events are counted from
the date of randomization. b Studies 1 and 2 regimens: doxorubicin and cyclophosphamide followed by paclitaxel (AC→T) or paclitaxel plus Herceptin (AC→TH). c Median duration of follow-up for Studies 1 and 2 combined was 8.3 years in the AC→TH arm. d Median follow-up duration of 12.6 months in the one-year Herceptin treatment arm. e Study 4 regimens: doxorubicin and cyclophosphamide followed by docetaxel (AC→T) or docetaxel plus Herceptin (AC→TH); docetaxel and carboplatin plus Herceptin (TCH). |
Figure 1 : Studies 1 and 2: Cumulative Incidence of
Time to First LVEF Decline of ≥ 10 Percentage Points from Baseline and to
Below 50% with Death as a Competing Risk Event
![]() |
Time 0 is initiation of paclitaxel or Herceptin + paclitaxel therapy.
Figure 2 : Study 3: Cumulative Incidence of Time to
First LVEF Decline of ≥ 10 Percentage Points from Baseline and to Below
50% with Death as a Competing Risk Event
![]() |
Time 0 is the date of randomization.
Figure 3 : Study 4: Cumulative Incidence of Time to
First LVEF Decline of ≥ 10 Percentage Points from Baseline and to Below
50% with Death as a Competing Risk Event
![]() |
Time 0 is the date of randomization.
The incidence of treatment emergent congestive heart failure among patients in the metastatic breast cancer trials was classified for severity using the New York Heart Association classification system (I-IV, where IV is the most severe level of cardiac failure) (see Table 2). In the metastatic breast cancer trials, the probability of cardiac dysfunction was highest in patients who received Herceptin concurrently with anthracyclines.
In Study 7, 5.0% of patients in the Herceptin plus chemotherapy arm compared to 1.1% of patients in the chemotherapy alone arm had LVEF value below 50% with a ≥10% absolute decrease in LVEF from pretreatment values.
Infusion Reactions
During the first infusion with Herceptin, the symptoms most commonly reported were chills and fever, occurring in approximately 40% of patients in clinical trials. Symptoms were treated with acetaminophen, diphenhydramine, and meperidine (with or without reduction in the rate of Herceptin infusion); permanent discontinuation of Herceptin for infusion reactions was required in < 1% of patients. Other signs and/or symptoms may include nausea, vomiting, pain (in some cases at tumor sites), rigors, headache, dizziness, dyspnea, hypotension, elevated blood pressure, rash, and asthenia. Infusion reactions occurred in 21% and 35% of patients, and were severe in 1.4% and 9% of patients, on second or subsequent Herceptin infusions administered as monotherapy or in combination with chemotherapy, respectively. In the post-marketing setting, severe infusion reactions, including hypersensitivity, anaphylaxis, and angioedema have been reported.
Anemia
In randomized controlled clinical trials, the overall incidence of anemia (30% vs. 21% [Study 5]), of selected NCI-CTC Grade 2-5 anemia (12.3% vs. 6.7% [Study 1]), and of anemia requiring transfusions (0.1% vs. 0 patients [Study 2]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. Following the administration of Herceptin as a single agent (Study 6), the incidence of NCI-CTC Grade 3 anemia was < 1%. In Study 7 (metastatic gastric cancer), on the Herceptin containing arm as compared to the chemotherapy alone arm, the overall incidence of anemia was 28% compared to 21% and of NCICTC Grade 3/4 anemia was 12.2% compared to 10.3%.
Neutropenia
In randomized controlled clinical trials in the adjuvant setting, the incidence of selected NCI-CTC Grade 4-5 neutropenia (1.7% vs. 0.8% [Study 2]) and of selected Grade 2-5 neutropenia (6.4% vs. 4.3% [Study 1]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. In a randomized, controlled trial in patients with metastatic breast cancer, the incidences of NCI-CTC Grade 3/4 neutropenia (32% vs. 22%) and of febrile neutropenia (23% vs. 17%) were also increased in patients randomized to Herceptin in combination with myelosuppressive chemotherapy as compared to chemotherapy alone. In Study 7 (metastatic gastric cancer) on the Herceptin containing arm as compared to the chemotherapy alone arm, the incidence of NCI-CTC Grade 3/4 neutropenia was 36.8% compared to 28.9%; febrile neutropenia 5.1% compared to 2.8%.
Infection
The overall incidences of infection (46% vs. 30% [Study 5]), of selected NCI-CTC Grade 2-5 infection/febrile neutropenia (24.3% vs. 13.4% [Study 1]) and of selected Grade 3-5 infection/febrile neutropenia (2.9% vs. 1.4% [Study 2]) were higher in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. The most common site of infections in the adjuvant setting involved the upper respiratory tract, skin, and urinary tract.
In Study 4, the overall incidence of infection was higher with the addition of Herceptin to AC-T but not to TCH [44% (AC-TH), 37% (TCH), 38% (AC-T)]. The incidences of NCI-CTC Grade 3-4 infection were similar [25% (AC-TH), 21% (TCH), 23% (AC-T)] across the three arms.
In a randomized, controlled trial in treatment of metastatic breast cancer, the reported incidence of febrile neutropenia was higher (23% vs. 17%) in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to chemotherapy alone.
Pulmonary Toxicity
Adjuvant Breast Cancer
Among women receiving adjuvant therapy for breast cancer, the incidence of selected NCI-CTC Grade 2-5 pulmonary toxicity (14.3% vs. 5.4% [Study 1]) and of selected NCI-CTC Grade 3-5 pulmonary toxicity and spontaneous reported Grade 2 dyspnea (3.4% vs. 0.9% [Study 2]) was higher in patients receiving Herceptin and chemotherapy compared with chemotherapy alone. The most common pulmonary toxicity was dyspnea (NCI-CTC Grade 2-5: 11.8% vs. 4.6% [Study 1]; NCI-CTC Grade 2-5: 2.4% vs. 0.2% [Study 2]).
Pneumonitis/pulmonary infiltrates occurred in 0.7% of patients receiving Herceptin compared with 0.3% of those receiving chemotherapy alone. Fatal respiratory failure occurred in 3 patients receiving Herceptin, one as a component of multi-organ system failure, as compared to 1 patient receiving chemotherapy alone.
In Study 3, there were 4 cases of interstitial pneumonitis in the one-year Herceptin treatment arm compared to none in the observation arm at a median follow-up duration of 12.6 months.
Metastatic Breast Cancer
Among women receiving Herceptin for treatment of metastatic breast cancer, the incidence of pulmonary toxicity was also increased. Pulmonary adverse events have been reported in the post-marketing experience as part of the symptom complex of infusion reactions. Pulmonary events include bronchospasm, hypoxia, dyspnea, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, and acute respiratory distress syndrome. For a detailed description, see WARNINGS AND PRECAUTIONS.
Thrombosis/Embolism
In 4 randomized, controlled clinical trials, the incidence of thrombotic adverse events was higher in patients receiving Herceptin and chemotherapy compared to chemotherapy alone in three studies (2.6% vs. 1.5% [Study 1], 2.5% and 3.7% vs. 2.2% [Study 4] and 2.1% vs. 0% [Study 5]).
Diarrhea
Among women receiving adjuvant therapy for breast cancer, the incidence of NCI-CTC Grade 2-5 diarrhea (6.7% vs. 5.4% [Study 1]) and of NCI-CTC Grade 3-5 diarrhea (2.2% vs. 0% [Study 2]), and of Grade 1-4 diarrhea (7% vs. 1% [Study 3; one-year Herceptin treatment at 12.6 months median duration of follow-up]) were higher in patients receiving Herceptin as compared to controls. In Study 4, the incidence of Grade 3-4 diarrhea was higher [5.7% AC-TH, 5.5% TCH vs. 3.0% AC-T] and of Grade 1-4 was higher [51% AC-TH, 63% TCH vs. 43% AC-T] among women receiving Herceptin. Of patients receiving Herceptin as a single agent for the treatment of metastatic breast cancer, 25% experienced diarrhea. An increased incidence of diarrhea was observed in patients receiving Herceptin in combination with chemotherapy for treatment of metastatic breast cancer.
Renal Toxicity
In Study 7 (metastatic gastric cancer) on the Herceptin-containing arm as compared to the chemotherapy alone arm the incidence of renal impairment was 18% compared to 14.5%. Severe (Grade 3/4) renal failure was 2.7% on the Herceptin-containing arm compared to 1.7% on the chemotherapy only arm. Treatment discontinuation for renal insufficiency/failure was 2% on the Herceptin-containing arm and 0.3% on the chemotherapy only arm.
In the post-marketing setting, rare cases of nephrotic syndrome with pathologic evidence of glomerulopathy have been reported. The time to onset ranged from 4 months to approximately 18 months from initiation of Herceptin therapy. Pathologic findings included membranous glomerulonephritis, focal glomerulosclerosis, and fibrillary glomerulonephritis. Complications included volume overload and congestive heart failure.
Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity. Among 903 women with metastatic breast cancer, human anti-human antibody (HAHA) to Herceptin was detected in one patient using an enzyme-linked immunosorbent assay (ELISA). This patient did not experience an allergic reaction. Samples for assessment of HAHA were not collected in studies of adjuvant breast cancer.
The incidence of antibody formation is highly dependent on the sensitivity and the 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 Herceptin with the incidence of antibodies to other products may be misleading.
Post-Marketing Experience
The following adverse reactions have been identified during post-approval use of Herceptin. 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.
- Infusion reaction [see WARNINGS AND PRECAUTIONS]
- Oligohydramnios or oligohydramnios sequence, including pulmonary hypoplasia, skeletal abnormalities, and neonatal death [see WARNINGS AND PRECAUTIONS]
- Glomerulopathy [see ADVERSE REACTIONS]
- Immune thrombocytopenia
- Tumor lysis syndrome (TLS): Cases of possible TLS have been reported in patients treated with Herceptin. 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 Herceptin (Trastuzumab)
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