Food and Drug Administration (FDA) approved Perjeta® (pertuzumab)* in combination with Herceptin® (trastuzumab) and docetaxel chemotherapy for people with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic breast cancer.1
The combination of Perjeta, trastuzumab and docetaxel chemotherapy was the only regimen that has been shown to significantly improve the time people with previously untreated HER2-positive metastatic breast cancer lived without their disease getting worse (median progression-free survival, or PFS, 18.5 vs. 12.4 months; 6.1 months improvement) compared to trastuzumab and docetaxel chemotherapy
3. PERJETA® is a first-line treatment for HER2positive metastatic breast cancer.
• PERJETA is an FDA-approved
treatment for HER2-positive
metastatic breast cancer. It is
a targeted therapy used as
part of a first-line HER2positive metastatic breast
cancer treatment plan, in
combination with Herceptin
(trastuzumab) and docetaxel
(chemotherapy).
5. PERJETA is referred to as a HER2
dimerization inhibitor (HDI).
• Learn more about HDIs.
6. HER family receptors are activated by ligand-induced
dimerization, or receptor pairing.3 Dimerization is a critical
step in HER family-mediated signaling, and HER receptors
are able to homodimerize or heterodimerize with
8. What is HER2-positive breast cancer?
All cells have HER2 receptors, including healthy cells and cancer cells. In
HER2-positive breast cancer, tumor cells have more HER2 receptors than
normal. Too much HER2 makes these cancer cells grow and divide too
rapidly.
NONCANCEROUS CELL
9. What is HER2-positive breast cancer?
All cells have HER2 receptors, including healthy cells and cancer cells. In HER2-positive breast
cancer, tumor cells have more HER2 receptors than normal. Too much HER2 makes these
cancer cells grow and divide too rapidly.
HER2-POSITIVE CANCER CELL
Cancer treatments called HER2-targeted therapies have been
developed to target the HER2 receptor.
PERJETA is one of those HER2-targeted therapies.
10. PERJETA is a targeted therapy for treating HER2-positive metastatic breast cancer.
PERJETA was designed to search
for and attack cancer cells with
too much HER2
HER2 tells cancer cells to grow by
sending signals
HER2 works by sending signals
that tell cells to grow and divide
One way that HER2 can send
signals is by pairing with other
HER receptors. This process is
called dimerization
11. PERJETA is a targeted therapy for treating HER2-positive metastatic breast cancer.
PERJETA works with Herceptin to target
HER2
PERJETA and Herceptin both target HER2
but work in different ways
PERJETA is thought to block one method
of signaling so that certain receptors are
unable to pair (dimerization) with HER2
Together, PERJETA and Herceptin are
thought to create a stronger blockade
against HER2 signals, helping to slow
down cancer cell growth
HER2 signaling could inhibit the growth of tumors.
13. PERJETA is proven to help control cancer growth
Adding PERJETA to Herceptin and docetaxel (chemotherapy) increased the time people
lived without their cancer growing or spreading by an average of 50%, compared with
people who took Herceptin and docetaxel (chemotherapy) alone
14. ERJETA helped people live longer
On average, people who were given PERJETA, Herceptin, and docetaxel
(chemotherapy) lived significantly longer than people given only Herceptin and
docetaxel (chemotherapy)
PERJETA is proven to shrink tumors
80% of people taking the PERJETA combination had their tumors shrink, compared to
69% of people taking Herceptin and docetaxel (chemotherapy) alonePeople who had
their tumors shrink maintained this response, on average, for 62% longer on the
PERJETA combination compared with people taking only Herceptin and docetaxel
(chemotherapy) (20.2 months vs 12.5 months)
PERJETA is taken together with Herceptin, another HER2 therapy
PERJETA is a targeted therapy used as part of a first-line HER2-positive metastatic
breast cancer treatment plan. This treatment plan includes Herceptin and docetaxel, a
type of chemotherapy. PERJETA and Herceptin both target HER2 but are believed to
work in complementary ways. The combination may increase death of cancer cells.
16. I. Introduction/General Information
A. Embryologically: belong to integument
B. Functionally: part of reproductive
system
1. Respond to sexual stimulation
2. Feed babies
17. Breast, continued …
C. Modified apocrine sweat glands
- apex of cell becomes part of secretion
and breaks off
D. Present in males and females
18. II. Anatomy
A. Position and Attachment
1. Lateral aspect of pectoral region
2.
3.
4.
5.
Located between ribs 3 and 6/7
Extend form sternum to axilla
Surrounded by superficial fascia
Rest on deep fascia
20. Position & attachment, continued ….
6. Fixed to skin & underlying
fascia by fibrous C.T. bands
a. Cooper’s (Suspensory)
Ligaments
b. Ligaments may retract when
breast tumors are present
22. Position & attachment, continued …
6. Left breast is usually slightly larger
7. Base is circular, either flattened or
concave
8. Separated from pectoralis major
muscle by fascia, retromammary
space
24. Anatomy, continued …
B. Structure
1. Outer surface convex, skin covered
2. Nipple:
a. At fourth intercostal space
b. Small conical/cylindrical
prominence below center
26. Structure, continued …
c. Surrounded by areola: pigmented
ring of skin
d. Thin skinned region lacking hair,
sweat glands
e. Contains areolar glands
27. Structure, continued …
3. Areola: contains dark pigment that
intensifies with pregnancy
a. Circular and radial smooth muscle fibers
b. Cause nipple erection
29. Structure, continued …
4. Each breast consists of ~ 20 lobes
of secretory tissue
a. Each lobe has one lactiferous duct
b. Lobes (and ducts) arranged radially
c. Embedded in connective tissue &
adipose of superficial fascia
d. Lobes composed of lobules
e. Lobules comprise alveoli
31. Structure, continued …
5. Excretory (lactiferous) ducts
converge toward areola
a. Form ampullae (collection sites of
lactiferous sinuses)
b. Ducts become contracted at base of
nipple
33. Structure, continued …
6. Secretory epithelium
a. Changes with hormonal signals
b. Onset of menstruation
c. Pregnancy (glands begin to enlarge at 2nd month)
d. After birth, 1st secretion is colostrom (contain
antibodies)
34. Structure, continued …
7. “Tail of Spence” = axillary tail
a. prolongation of upper, outer
quadrant in axillary direction
b. Passes under axillary fascia
c. May be mistaken for axillary lymph
nodes
36. Structure, continued …
8. Fatty Tissue: surrounds surface, fills
spaces between lobes
a. Determines form & size of breast
b. No fatty deposit under nipple &
areola
38. Structure, continued …
C. Vessels & nerves
1. Arteries: derived from thoracic
branches of three pairs of arteries
a. Axillary arteries
1) continuous with subclavian a.
2) gives rise to external mammary
( = lateral thoracic) artery
39. Vessels & Nerves, continued …
b. Internal mammary (thoracic) arteries
1) first descending branch of
subclavian artery
2) supply intercostal spaces & breast
3) used for coronary bypass surgery
c. Intercostal arteries:
1) numerous branches from internal
& external mammary arteries
2) supply intercostal spaces & breast
40. Arterial Supply to the Breast
Subclavian a.
Axillary a.
External
mammary
(thoracic) a.
Internal
mammary
(thoracic) a.
41. Vessels & Nerves, continued …
2. Veins:
a. form a ring around the base of the
venosus”)
nipple (“circulus
b. Large veins pass from circulus venosus to circumference of
mammary gland, then to
c. External mammary v to axillary v
or
d. Internal mammary v to subclavian v
43. Breast Anatomy, con’t…
3. Innervation: derived from:
a. anterior & lateral cutaneous
nerves of thorax
b. spinal segments T3 – T6
44. Structure, continued …
4. Lymphatics: clinically significant!
a. Glandular lymphatics drain into anterior axillary (pectoral)
nodes
central axillary nodes apical nodes
deep cervical nodes
subclavicular (subclavian) nodes
b. Medial quadrants drain into parasternal nodes
45. Lymph Nodes of the Breast
Subclavian
nodes
Axillary
nodes
Lateral
pectoral
nodes
Parasternal
nodes
46. Lymphatics, continued …
c. Superficial regions of skin, areola, nipples:
-form large channels & drain into pectoral nodes
d. NOTE: axillary nodes also drain lymph from arm
48. Routes of Metastasis
• From medial lymphatics to parasternal nodes
– Then to mediastinal nodes
• Across the sternum in lymphatics to
opposite side via cross-mammary pathways
– Then to contralateral breast
• From subdiaphragmatic lymphatics to nodes in
abdomen
– Then to liver, ovaries, peritoneum
49. Major Routes of Metastasis
Channels to Contralateral Breast
Axillary Lymph Channels
Subdiaphragmatic Lymph Channels
50. Structure, continued …
D. Anomalies
1. Inverted nipple: congenital or due
to cancer
2. Ectopic nipple:
a. “polythelia” or “hyperthelia”
b. additional nipples along milk line
3. Amastia
4. Micromastia
51. Anomalies, continued …
5. Macromastia
6. Gynecomastia
a. breast development of male in areolar region
b. noted in males who smoke marijuana at
puberty
52. III. Diseases of the Breast
A. Most are readily detectable
B. Etiology unknown, influencing factors
1. Sex
2. Heredity
53. Diseases of the breast, continued …
3. Endocrine influence
a. Menstruation – tenderness from fluid engorgement
b. Post-menopause
1) decrease of fibro-cystic disease
2) increase in cancer
c. Pregnancy
54. Diseases of the Breast, continued …
C. General symptoms & signs
1. Nipple discharge
a. always significant if not pregnant.
b. May be due to benign pituitary tumor.
2. Local pain, tenderness
3. Duration of lesion
4. Size, rate of growth
55. Symptoms & Signs, continued …
5. Retraction sign: “dimpling” involving
skin, nipple or areola
6. Mobility of mass
a. Benign = movable
1) not attached
2) not invasive
b. Malignant = attached
1)May grow into bone
56. Symptoms & Signs, continued …
7. Consistency of mass
a. Cysts = fluctuant; compressible
b. Fibroadenoma = rubbery
c. Carcinoma = firm, hard (like gravel)
8. Axillary area lymph node enlargement
57. D. Benign breast conditions
1. Infection = usually during or after
lactation
a. Recurrent, subareolar abscess
b. TB of the breast
2. Trauma = contusion
3. Hypertrophy = seen in either sex at adolescence
a. Gynecomastia = in males
58. Hypertrophy, continued …
b.
Other causes
1) testicular or pituitary tumor
2) cirrhosis
3) hypogonadism = not enough testosterone
4) estrogen administration for prostate cancer
60. Breast cancer originates in breast
tissue and arises from the ductal
tissue of the breast and, less
commonly, the lobulartissue. There
are several forms of breast cancer
based, in part, on cellular and
genetic characteristics,
62. HER2-Positive
Overabundance of the HER2 protein
classifies the breast cancer as HER2positive and causes breast cancer
cells to multiply, spread more rapidly,
and survive longer than other
breast cancers
64. Hormone Receptor-Positive
Breast cancer cells that express
hormone receptors for estrogen
(ER) and/or progesterone (PR)
are dependent on the signaling
of those receptors
72. Mammography
• Use a low-dose x-ray system to examine
breasts
• Digital mammography replaces x-ray
film by solid-state detectors that
convert x-rays into electrical signals.
These signals are used to produce images
that can be displayed on a computer
screen (similar to digital cameras)
• Mammography can show changes in the
breast up to two years before a
physician can feel them
72
73. Computer-Aided Diagnosis
• Mammography allows for efficient
diagnosis of breast cancers at an
earlier stage
• Radiologists misdiagnose 10-30%
of the malignant cases
• Of the cases sent for surgical
biopsy, only 10-20% are
actually malignant
CAD systems
can assist
radiologists to
Reduce these
problems
National Cancer Institute
73
74. What Mammograms Show
Two of the most important mammographic
indicators of breat cancers
– Masses
– Microcalcifications: Tiny flecks of calcium – like
grains of salt – in the soft tissue of the breast
that can sometimes indicate an early cancer.
74
75. Detection of Malignant Masses
Malignant masses have a more spiculated
appearance
benign
malignant
75
76. Mammogram – Difficult Case
• Heterogeneously dense breast
• Cancer can be difficult to
detect with this type of
breast tissue
• The fibroglandular tissue
(white areas) may hide the
tumor
• The breasts of younger
women contain more glands
and ligaments resulting in
dense breast tissue
76
77. Mammogram – Easier Case
• With age, breast tissue
becomes fattier and has
fewer glands
• Cancer is relatively easy
to detect in this type of
breast tissue
77
78. Different Views
Side-to-Side
MRI - Cancer can have a unique
appearance – many small irregular
white areas that turned out to be
cancer (used for diagnosis)
Top-to-Bottom
78
81. Tumors and Cysts, con’t…
b. Breast Cyst
1. Benign
2. May be aspirated
if large
82. Benign conditions, continued …
c. Fibrocystic breast
changes
1) 20%+ of remenopausal
women
2) discomfort, cysts
3) treatment rarely
required
4) More likely to not
detect a developing
cancer
83. Tumors & cysts, continued ….
d. Intraductal papilloma
- may produce “chocolate”
or
bloody
discharge from nipple
e. Lipoma: common
- fatty tumors
84. Carcinoma of the breast
1.
Most common malignant tumor among
women
2. 1/8 of women will develop breast cancer
a. 1/6 in Orange County
b. 1/5 in San Francisco
3. Generally no discomfort
86. Carcinoma of breast, continued …
4.
Physical signs:
a.
b.
c.
d.
e.
Slowly growing, painless mass
May demonstrate retracted nipple
May be bleeding from nipple
May be distorted areola, or breast contour
Skin dimpling in more advanced stages with
retraction of Cooper’s ligaments
87. Physical signs, continued …
f. Attachment of mass
g. Edema of skin
1)with “orange skin” appearance (peau d’orange)
2) due to blocked lymphatics
h. Enlarged axillary or deep cervical lymph nodes
88. Breast Cancer, con’t…
5. Common sites for metastasis
a. Lungs & pleura
b. Skeleton system (skull, vertebral column,
pelvis)
c. Liver
6. Atypical carcinomas
a. Inflammatory carcinoma (hormonal,
chemotherapy)
b. Paget’s disease of the breast
pagget's
disease
89. Scalar Field
• A scalar field is a n-dimensional space
with a scalar value attached to each
point in the space (e.g., a gray-scale
image)
89
90. Scalar Field and Gradient
• A scalar field is a n-dimensional space
with a scalar value attached to each
point in the space (e.g., a gray-scale
image)
• The derivative of a scalar field results
in a vector field called the gradient
– i.e., the gradient is a vector field
• which points in the direction of the greatest
rate of increase of the scalar field, and
• whose magnitude is the greatest rate of change
90
Black representing
Higher values
91. Gradient
The derivative of a scalar field
results in a vector field called
the gradient
– i.e., the gradient is a vector
field
• which points in the direction of
the greatest rate of increase
of the scalar field, and
• whose magnitude is the
greatest rate of change
91
Black representing
Higher values
92. Cartesian Gradient
g (P )
For an image function
I(P) where P is a pixel,
the Cartesian gradient
at P is:
I ( P)
92
I ( P)
y
I ( P)
x
tan
Magnitude:
Orientation:
arctan
P
x
I ( P)
y
g ( P)
( P)
(P)
I ( P)
y
I ( P)
x
m( P)
I ( P)
x
2
I ( P)
y
2
I ( P)
y
I ( P)
x
93. Radial Gradient
• The radial gradient
vector has the same
magnitude as the
Cartesian gradient
vector, but
• the orientation is given
as:
r ( P)
93
( P)
( P)
Radial gradient
r(P)
g (P )
(P)
P
(P)
94. Feature: Spiculation
[Huo et al.]
• Extract the mass using a
region-growing technique
• The maximum gradient and
its angle relative to the
radial direction are
computed
• Calculate the full-width at
half-maximum (FWHM)
from the cumulative
gradient orientation
histogram
94
95. Feature: Spiculation [Chan et al.]
• Determine the outline of
the segmented mass
• Obtain the rubber-bandstraightening-transformed
image
– The spicules become
approximately aligned in a
similar direction
• The rectangular region can
then be subjected to
texture analysis
95
96. Breast Calcifications
• Calcifications show up as
white spots on a mammogram
• Round well-defined, larger
calcifications (left column)
are more likely benign
• Tight cluster of tiny,
irregularly shaped
calcifications (right column)
may indicate cancer
96
97. Calcification Features
• The morphology of individual
calcification, e.g., shape, area,
and brightness
• The heterogeneity of
individual features
characterized by the mean,
the standard deviation, and
the maximum value for each
feature.
• Cluster features such as total
area, compactness
97
98. Database Approach to
Computer-Aided Diagnosis
Content-based image retrieval techniques can provide radiologists
“visual aids” to increase confidence in their diagnosis
• The database consists of a large
number of images with verified
pathology results
• Diagnosis is done by submitting
the suspected mass region as a
query to retrieve similar cases
from the database
98
99. A Mammography CAD System
[Giger et al.]
Probability of
malignancy
Similar images of
known diagnosis
Indicates the unknown
lesion relative to all
lesions in the database
99
101. DESCRIPTION
PERJETA® (Pertuzumab)is a recombinant humanized monoclonal
antibody that targets the extracellular dimerization domain
(Subdomain II) of the human epidermal growth factor receptor 2
protein (HER2). Pertuzumab is produced by recombinant DNA
technology in a mammalian cell (Chinese Hamster Ovary) culture
containing the antibiotic, gentamicin. Gentamicin is not detectable
in the final product. Pertuzumab has an approximate molecular
weight of 148 kDa.
PERJETA is a sterile, clear to slightly opalescent, colorless to pale
brown liquid for intravenous infusion. Each single use vial contains
420 mg of pertuzumab at a concentration of 30 mg/mL in 20 mM
L-histidine acetate (pH 6.0), 120 mM sucrose and 0.02%
polysorbate 20.
PERJETA® is a first-line treatment for HER2-positive metastatic breast cancer.
103. PERJETA® is a first-line treatment for HER2-positive metastatic breast cancer.
104. Pharmacokinetics
PERJETA® Pertuzumab demonstrated linear
pharmacokinetics at a dose range of 2 – 25
mg/kg. Based on a population PK analysis that
included 481 patients, the median clearance
(CL) of pertuzumab was 0.24 L/day and the
median half-life was 18 days. With an initial
dose of 840 mg followed by a maintenance
dose of 420 mg every three weeks thereafter,
the steady-state concentration of pertuzumab
was reached after the first maintenance dose.
PERJETA® is a first-line treatment for HER2-positive metastatic breast cancer.
105. INDICATIONS AND USAGE
1.1 Metastatic Breast Cancer (MBC)
PERJETA is indicated for use in
combination with trastuzumab and
docetaxel for the treatment of patients
with HER2-positive metastatic breast
cancer who have not received prior antiHER2 therapy or chemotherapy for
metastatic disease.
PERJETA® is a first-line treatment for HER2-positive metastatic breast cancer.
106. INDICATIONS AND USAGE
1.2 Neoadjuvant Treatment of Breast Cancer
PERJETA is indicated for use in combination with
trastuzumab and docetaxel for the 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. This
indication is based on demonstration of an improvement
in pathological complete response rate. No data are
available demonstrating improvement in event-free
survival or overall surviva
PERJETA® is a first-line treatment for HER2-positive metastatic breast cancer.
107. DOSAGE AND ADMINISTRATION
The initial dose of PERJETA is 840 mg administered as a
60-minute intravenous infusion, followed every 3
weeks by a dose of 420 mg administered as an
intravenous infusion over 30 to 60 minutes.
When administered with PERJETA, the recommended
initial dose of trastuzumab is 8 mg/kg administered as a
90-minute intravenous infusion, followed every 3
weeks by a dose of 6 mg/kg administered as an
intravenous infusion over 30 to 90 minutes.
PERJETA® is a first-line treatment for HER2-positive metastatic breast cancer.
108. DOSAGE AND ADMINISTRATION
Metastatic Breast Cancer (MBC)
When administered with PERJETA, the
recommended initial dose of docetaxel is 75
mg/m2 administered as an intravenous infusion.
The dose may be escalated to 100 mg/m2
administered every 3 weeks if the initial dose is
well tolerated.
PERJETA® is a first-line treatment for HER2-positive metastatic breast cancer.
109. DOSAGE AND ADMINISTRATION
Neoadjuvant Treatment of Breast Cancer
PERJETA should be administered every 3 weeks for 3 to 6 cycles as part of one of the
following treatment regimens for early breast cancer [see Clinical Studies (14.2)]:
Four preoperative cycles of PERJETA in combination with trastuzumab and docetaxel
followed by 3 postoperative cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) as
given in Study 2
Three preoperative cycles of FEC alone followed by 3 preoperative cycles of PERJETA in
combination with docetaxel and trastuzumab as given in Study 3
preoperative cycles of PERJETA in combination with docetaxel, carboplatin, and
Six
trastuzumab (TCH) (escalation of docetaxel above 75 mg/m2 is not recommended) as given
in Study 3
Following surgery, patients should continue to receive trastuzumab to complete 1 year of
treatment. There is insufficient evidence to recommend continued use of PERJETA for greater
than 6 cycles for early breast cancer. There is insufficient evidence to recommend
concomitant administration of an anthracycline with PERJETA, and there are no safety data
to support sequential use of doxorubicin with PERJETA.
PERJETA® is a first-line treatment for HER2-positive metastatic breast cancer.
110. DOSAGE AND ADMINISTRATION
Dose Modification
For delayed or missed doses, if the time between two sequential
infusions is less than 6 weeks, the 420 mg dose of PERJETA should be
administered. Do not wait until the next planned dose. If the time
between two sequential infusions is 6 weeks or more, the initial dose of
840 mg PERJETA should be re-administered as a 60-minute intravenous
infusion followed every 3 weeks thereafter by a dose of 420 mg
administered as an intravenous infusion over 30 to 60 minutes.
PERJETA should be discontinued if trastuzumab treatment is
discontinued.
Dose reductions are not recommended for PERJETA.
PERJETA® is a first-line treatment for HER2-positive metastatic breast cancer.
111. Preparation for Administration
Administer as an intravenous infusion only. Do not administer as an
intravenous push or bolus. Do not mix PERJETA with other drugs.
Preparation
Prepare the solution for infusion, using aseptic technique, as follows:
1. Parenteral drug products should be inspected visually for particulates and
discoloration prior to administration.
2. Withdraw the appropriate volume of PERJETA solution from the vial(s).
3. Dilute into a 250 mL 0.9% sodium chloride PVC or non-PVC polyolefin
infusion bag.
4. Mix diluted solution by gentle inversion. Do not shake.
5. Administer immediately once prepared.
6. If the diluted infusion solution is not used immediately, it can be stored at
2oC to 8oC for up to 24 hours.
7. Dilute with 0.9% Sodium Chloride injection only. Do not use dextrose (5%)
solution.
PERJETA® is a first-line treatment for HER2-positive metastatic breast cancer.
112. DOSAGE FORMS AND STRENGTHS
PERJETA (pertuzumab) 420 mg/14 mL
(30 mg/mL) in a single-use vial
CONTRAINDICATIONS
PERJETA is contraindicated in patients with known
hypersensitivity to pertuzumab or to any of its
excipients.
PERJETA® is a first-line treatment for HER2-positive metastatic breast cancer.
113. HER2 Testing
Detection of HER2 protein overexpression is necessary for selection of patients
appropriate for PERJETA therapy because these are the only patients studied
and for whom benefit has been shown [see Indications and Usage (1) and
Clinical Studies (14)]. Patients with breast cancer were required to have
evidence of HER2 overexpression defined as 3+ IHC or FISH amplification ratio
2.0 in the clinical studies. Only limited data were available for patients,whose
breast cancer was positive by FISH, but did not demonstrate protein
overexpression by IHC.
114. HER2 Testing
Assessment of HER2 status should be performed by laboratories using FDAapproved tests with demonstrated proficiency in the specific technology being
utilized. Improper assay performance, including use of sub-optimally fixed tissue,
failure to utilize specified reagents, deviation from specific assay instructions, and
failure to include appropriate controls for assay validation, can lead to unreliable
results.
115. ADVERSE REACTIONS
Metastatic Breast Cancer
1. The most common adverse reactions (> 30%) with PERJETA in
combination with trastuzumab and docetaxel were diarrhea, alopecia,
neutropenia, nausea, fatigue, rash, and peripheral neuropathy.
Neoadjuvant Treatment of Breast Cancer
1. The most common adverse reactions (> 30%) with PERJETA in
combination with trastuzumab and docetaxel were alopecia, diarrhea,
nausea, and neutropenia.
2. 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.
3. 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.