An estimated 2240 men
and 232,340 women will
be diagnosed with invasive
breast cancer in 2013,
and an estimated 410 men
and 39,620 women will die
from their disease ( 1).
Table 10: Currently Approved Human Epidermal Growth
Factor 2 (HER2) Targeted Drugs
Generic Name Trade Name Formulation
ado-trastuzumab emtansine Kadcyla
Molecularly Targeted Therapies
Research is continually expanding our understanding of cancer biology, making it increasingly possible
to link specific defects in the molecular machinery of cells to cancer development. This knowledge is
directly enabling the development of medicines that precisely target these alterations and block their
ill effects. As a result, the standard of care is transforming from a one-size-fits-all approach to one
in which the molecular makeup of the patient and of the tumor dictate the best therapeutic strategy.
This approach is variously called personalized cancer medicine, molecularly based medicine, precision
medicine, or tailored therapy.
The number of molecularly targeted therapies approved by the FDA is increasing, and is expected to
continue to grow as our knowledge of cancer biology expands. Because of the greater precision of many
of the newest cancer medicines, they are more effective and less toxic than the treatments that have
been the mainstay of patient care for decades. Thus, these new medicines are not only saving the lives of
countless cancer patients, but are also improving their quality of life.
A Direct Hit: Targeting Chemotherapy to Breast Cancer
It is anticipated that in 2013, more than 45,000 individuals in the United States will be diagnosed with
breast cancer that overexpresses the protein HER2 ( 1, 132). HER2-positive breast cancer tends to be
aggressive, and the outcome for patients is typically poor. Decades of research led to the development
and FDA approval of three HER2-targeted therapies that have revolutionized the treatment of this disease:
trastuzumab (Herceptin), lapatinib (Tykerb), and pertuzumab (Perjeta) (see Table 10). These drugs
significantly prolong survival for patients with metastatic disease when given together with standard
chemotherapies (133-135). Unfortunately, some patients fail to respond to treatment, and in most of
those who do respond initially, the disease ultimately progresses. As a result, new therapies for this
subtype of breast cancer are urgently needed and are being actively researched.
An exciting new treatment for patients with metastatic HER2-positive breast cancer, like Kim Alexander,
was approved by the FDA in February 2013. The drug, ado-trastuzumab emtansine (Kadcyla), which
was referred to as T-DM1 during clinical development, is an antibody-drug conjugate. Antibody-drug conjugates are a new type of targeted anticancer therapy, which use an antibody to deliver an
attached drug directly to those cancer cells that display the antibody’s target on their surfaces. This
precision reduces the side effects of the drugs compared with traditional chemotherapy that is delivered
systemically. In the case of T-DM1, the chemotherapy DM1 is attached to the antibody trastuzumab
using a stable linker. The HER2-targeting properties of trastuzumab allow T-DM1 to be delivered directly
to HER2-positive cells. The result is a significant improvement in survival for many patients (132).
The development of antibody-drug conjugates is an intensively studied area of cancer research that is
showing great promise for near-term patient benefit. In the United States alone, approximately 80 clinical
trials are either ongoing or actively recruiting patients to test antibody-drug conjugates as a treatment for