Drugs that target the HER2/neu protein

Drugs that target the HER2/neu protein

Trastuzumab (Herceptin): Trastuzumab is a type of drug known as a monoclonal
antibody—a man-made version of a very specific immune system protein. It attaches to a
growth-promoting protein known as HER2/neu (or just HER2), which is present in larger
than normal amounts on the surface of the breast cancer cells in about 1 of 5 patients.
Breast cancers with too much of this protein tend to grow and spread more aggressively.
Trastuzumab can help slow this growth and may also stimulate the immune system to
more effectively attack the cancer.
Trastuzumab is given as an injection into a vein (IV), usually once a week or as a larger
dose every 3 weeks. The optimal length of time to give it is not yet known.
Trastuzumab is often used (along with chemo) as adjuvant therapy for HER2-positive
cancers to reduce the risk of recurrence. It is given with chemo at first, and then given on
its own, usually for a total of a year of treatment. This may also be started before surgery
as neoadjuvant therapy. Although this drug is usually given for a year, studies are looking
at how long this drug needs to be given to be most effective.
Trastuzumab is also used to treat HER2-positive advanced breast cancers that return after
chemo or continue to grow during chemo. Treatment that combines trastuzumab with
chemo generally works better than chemo alone. If a cancer gets worse while a patient is
getting trastuzumab and chemo, often the trastuzumab is continued and the chemo is
changed.
Compared with chemo drugs, the side effects of trastuzumab are relatively mild. These
side effects are rare and may include fever and chills, weakness, nausea, vomiting, cough,
diarrhea, and headache. These side effects are generally mild and occur less often after
the first dose.
A more serious potential side effect is heart damage leading to a problem called
congestive heart failure. For most (but not all) women, this effect has been temporary and
has improved when the drug is stopped. The risk of heart problems is higher when
trastuzumab is given with certain chemo drugs such as doxorubicin (Adriamycin) and
epirubicin (Ellence). For this reason heart function is checked regularly during treatment
with trastuzumab. Major symptoms of congestive heart failure are shortness of breath, leg
swelling, and severe fatigue. Women having these symptoms should call their doctor
right away.

Trastuzumab should not be given to women who are pregnant because it may harm and
even cause death to the fetus. Women who could become pregnant need to use effective
birth control during treatment.
Pertuzumab (Perjeta™): Like trastuzumab, pertuzumab is a monoclonal antibody that
attaches to the HER2 protein. It seems to target a different part of the protein than
trastuzumab does. This drug is used to treat advanced breast cancer. When given along
with docetaxel (Taxotere) and trastuzumab to patients who have not yet received
chemotherapy for their advanced breast cancer, it has been shown to cause tumors to
shrink or stop growing for about 6 months longer than giving docetaxel and trastuzumab
alone.
This drug is given as an infusion into a vein every 3 weeks. When given with
trastuzumab and docetaxel, common side effects included diarrhea, hair loss, nausea,
fatigue, rash, and low white blood cell counts (sometimes with fever). Many side effects,
such as hair loss, nausea, and fatigue occur at about the same rate as in those who get just
docetaxel and trastuzumab.
This drug caused fetal harm and even death of the fetus in animal studies, so it should not
be given to women who are pregnant. Women who could become pregnant need to use
effective birth control during treatment. Although so far it has not been shown to affect
heart function, there is concern that it can, so it cannot be given to patients with poor
heart function. As with trastuzumab, your doctor will check tests of heart function every
few months while you are treated with this drug.
Lapatinib (Tykerb): Lapatinib is another drug that targets the HER2 protein. This drug
is given as a pill to women with advanced HER2-positive breast cancer that is no longer
helped by chemo and trastuzumab. It is also being studied as an adjuvant therapy in
patients with HER2-positive cancer. The chemo drug capecitabine (Xeloda) is often
given in combination with lapatinib to treat metastatic breast cancer. It may also be given
with letrozole (Femara) in patients with HER2-positive advanced breast cancer that is
also ER-positive.

In one study, giving lapatinib along with trastuzumab helped patients with advanced
breast cancer live longer than giving it alone.
The most common side effects of this drug include diarrhea, nausea, vomiting, rash, and
hand-foot syndrome (this was discussed in the section about chemotherapy). Diarrhea is a
common side effect and can be severe, so it is very important to let your health care team
know about any changes in bowel habits as soon as they happen.
In rare cases lapatinib may cause liver problems or a decrease in heart function (that can
lead to shortness of breath), although this seems to go away once treatment is finished.
Everolimus (Affinitor®)
Everolimus is a type of targeted therapy that blocks mTOR, a protein in cells that
normally promotes their growth and division. By blocking this protein, everolimus can
help stop cancer cells from growing. Everolimus may also stop tumors from developing
new blood vessels, which can help limit their growth. In treating breast cancer, this drug
seems to help hormone therapy drugs work better.
Everolimus is a pill taken once a day.
This drug was recently approved to treat advanced hormone receptor−positive,
HER2−negative, breast cancer in women who have gone through menopause. It is meant
to be used with exemestane (Aromasin) in these women if their cancers have grown while
they were being treated with either letrozole or anastrazole. This approval was based on a
study that showed that giving everolimus with exemestane was better than exemestane
alone in shrinking tumors and stopping their growth in post-menopausal women with
hormone receptor−positive, HER2−negative breast cancer that had stopped responding to
letrozole or anastrazole.
Common side effects of this drug include mouth sores, diarrhea, nausea, fatigue, feeling
weak or tired, low blood counts, shortness of breath, and cough. Everolimus can also
increase blood lipids (cholesterol and triglycerides) and blood sugars, so your doctor will
check your blood work periodically while you are on this drug. It can also increase your
risk of serious infections, so your doctor will watch you closely for infection while you
are on treatment.
Everolimus is also being studied for use with other hormone therapy drugs and for earlier
stage breast cancer. This is discussed further in the section, “What’s new in breast cancer
research and treatment?”