FDA Advisory Committee Recommends Accelerated Approval of Genentech’s
Perjeta for Neoadjuvant Use in HER2-Positive Early Stage Breast Cancer
*The FDA Will Make a Final Decision by October 31
*The Perjeta Regimen is the First Potential Treatment to be Reviewed by the
FDA for Neoadjuvant Use in Breast Cancer
SILVER SPRING, Md. -- September 12, 2013
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today
announced that the U.S. Food and Drug Administration’s (FDA) Oncologic Drugs
Advisory Committee (ODAC) voted 13 to 0, with one abstention, in favor of
recommending accelerated approval of a Perjeta^® (pertuzumab) regimen for
neoadjuvant treatment (use before surgery) in people with high-risk,
HER2-positive early stage breast cancer. The FDA will make a decision on
whether or not to approve Perjeta for this use by October 31, 2013. If
approved, the Perjeta regimen will be the first neoadjuvant breast cancer
treatment approved in the United States and the first treatment approved based
on pathological complete response (pCR) data, meaning there is no tumor tissue
detectable at the time of surgery.
Perjeta is already approved in a number of countries including the United
States for people with HER2-positive metastatic breast cancer (an advanced
form of the disease in which the cancer has spread to other parts of the
The Perjeta application for neoadjuvant use follows a proposed new FDA pathway
designed to more quickly bring promising medicines to people with earlier
stages of breast cancer, where treatment may have a greater impact.
“More than 6,000 people in the United States die of HER2-positive breast
cancer each year,” said Hal Barron, M.D., chief medical officer and head,
Global Product Development. “The ODAC’s recommendation is a step toward
bringing Perjeta to people with HER2-positive early stage breast cancer, where
treatment can potentially prevent the disease from returning and spreading.”
Neoadjuvant treatment may allow a doctor to quickly assess whether a medicine
is working and may also reduce a tumor's size so it is easier to surgically
remove. pCR is a common measure of neoadjuvant treatment effect in breast
cancer and can be assessed more quickly than traditional endpoints in early
stage breast cancer.
The ODAC recommendation was based on a review of results from NEOSPHERE and
TRYPHAENA, two Phase II studies of Perjeta in high-risk, HER2-positive early
stage breast cancer, as well as on longer-term safety data from the Phase III
CLEOPATRA study of Perjeta in HER2-positive metastatic breast cancer.
The ongoing Phase III APHINITY study will further evaluate Perjeta in the
adjuvant setting (after surgery) and compares Perjeta, Herceptin^®
(trastuzumab) and chemotherapy with Herceptin and chemotherapy in people with
HER2-positive early stage breast cancer. The study has completed enrollment
with approximately 4,800 people, and the primary endpoint is invasive
disease-free survival (IDFS). Genentech has proposed this study as a
confirmatory study to the FDA. Data are expected in 2016.
About the NEOSPHERE Study
The NEOSPHERE study (NeoadjuvantStudy ofPertuzumab andHerceptin in an Early
Regimen Evaluation) is a randomized, multicenter, international Phase II study
that was conducted in 417 people with newly diagnosed HER2-positive, locally
advanced, inflammatory or early stage breast cancer with tumors greater than
two centimeters. Participants were randomized to four study arms and received
four cycles (12 weeks) of neoadjuvant treatment. The primary endpoint was pCR.
Secondary endpoints included clinical response, time to clinical response,
safety profile, disease-free survival (DFS), breast-conserving surgery rate
and biomarker assessment. Study data showed the following:
*Treatment with Perjeta, Herceptin and docetaxel chemotherapy significantly
improved the rate of total pCR by 17.8 percent compared to Herceptin and
docetaxel alone (39.3 percent vs. 21.5 percent, p=0.0063).
*pCR of 21.5 percent for Herceptin and docetaxel
*pCR of 39.3 percent for Perjeta, Herceptin and docetaxel
*pCR of 11.2 percent for Perjeta and Herceptin
*pCR of 17.7 percent for Perjeta and docetaxel
*The most common severe (Grade 3 or higher) AEs for the Perjeta regimen
were neutropenia (decrease in a certain type of white blood cell, 44.9
percent), febrile neutropenia (fever associated with decrease in a certain
type of white blood cell,
8.4 percent) and diarrhea (5.6 percent).
About the TRYPHAENA Study
The TRYPHAENA study (ToleRabilitY of Pertuzumab, Herceptin and AnthracyclinEs
in NeoAdjuvant breast cancer) is a randomized, multicenter Phase II study that
was conducted in 225 people with HER2-positive, locally advanced, inflammatory
or early stage breast cancer with tumors greater than two centimeters.
Participants were randomized to one of three neoadjuvant Perjeta regimens. The
primary endpoint was cardiac safety. Secondary endpoints included pCR,
clinical response, breast-conserving surgery rate, DFS, progression-free
survival (PFS), overall survival (OS) and biomarker assessment. Study data
showed the following:
*The study was not powered to compare the three study arms. The rates of
total pCR in the three arms were as follows:
*pCR of 56.2 percent for Perjeta, Herceptin and anthracycline-based
chemotherapy, followed by Perjeta, Herceptin and docetaxel
*pCR of 54.7 percent for anthracycline-based chemotherapy, followed by
Perjeta, Herceptin and docetaxel
*pCR of 63.6 percent for the anthracycline-free arm (Perjeta,
Herceptin, docetaxel and carboplatin chemotherapy)
*No new or unexpected cardiac AEs, or other AEs, were observed in any of
the study arms. AEs observed were consistent with those seen in previous
studies of Perjeta, Herceptin and chemotherapy, either in combination or
*The most common severe AEs in any of the three study arms were:
*In the concurrent arm: neutropenia (47.2 percent), leukopenia
(decrease in overall white blood cells, 19.4 percent) and febrile
neutropenia (18.1 percent)
*In the sequential arm: neutropenia (42.7 percent), leukopenia (12.0
percent) and febrile neutropenia (9.3 percent)
*In the anthracycline-free arm: neutropenia (46.1 percent), febrile
neutropenia (17.1 percent), anemia (decrease in red blood cells, 17.1
percent); the AEs of diarrhea, leukopenia, anemia and
thrombocytopenia (decrease in platelets) all had an incidence of 11.8
Perjeta is a medicine that targets the HER2 receptor, a protein found on the
outside of many normal cells and in high quantities on the outside of cancer
cells in HER2-positive cancers. Perjeta is designed specifically to prevent
the HER2 receptor from pairing (or “dimerizing”) with other HER receptors
(EGFR/HER1, HER3 and HER4) on the surface of cells, a process that is believed
to play a role in tumor growth and survival. Binding of Perjeta to HER2 may
also signal the body’s immune system to destroy the cancer cells. The
mechanisms of action of Perjeta and Herceptin are believed to complement each
other, as both bind to the HER2 receptor, but to different places. The
combination of Perjeta and Herceptin is thought to provide a more
comprehensive blockade of HER signaling pathways.
About Genentech and Roche in HER2-positive Breast Cancer
Genentech and Roche have spent more than 30 years studying the role of HER2 in
cancer, and Perjeta is a result of this research. A companion diagnostic test
is used to determine if a person is HER2-positive and whether treatment with
Perjeta and Herceptin is appropriate.
Perjeta Indication Statement
Perjeta is approved for use in combination with Herceptin and docetaxel
chemotherapy in people with HER2-positive breast cancer that has spread to
different parts of the body (metastatic) and who have not received anti-HER2
therapy or chemotherapy for metastatic disease.
Important Safety Information
*Because side effects from this treatment are common, it is important to
know what side effects may happen and what symptoms patients should watch
*A patient’s doctor may stop treatment if serious side effects happen.
Patients must contact their healthcare team right away if they have
questions or are worried about any side effects.
Most Serious Side Effect of Perjeta
Receiving Perjeta during pregnancy can result in the death of an unborn baby
and birth defects.
*Birth control should be used while receiving Perjeta and for six months
after a patient’s last dose of Perjeta. Patients who are breastfeeding
should talk with their doctor about either stopping breastfeeding or
stopping treatment with Perjeta.
*If a patient thinks she may be pregnant, she should contact her healthcare
*If a patient is exposed to Perjeta during pregnancy, she is encouraged to
enroll in the MotHER Pregnancy Registry by contacting (800) 690-6720.
Other Possible Serious Side Effects
*Heart problems: Perjeta can result in heart problems, including those
without symptoms (such as reduced heart function) and those with symptoms
(such as congestive heart failure). A patient’s doctor may run tests to
monitor the patient’s heart function before and during treatment with
*Infusion-related reactions: Perjeta is a medicine that is delivered into a
vein through a needle. This process can cause reactions known as
infusion-related reactions. The most common infusion-related reactions
when receiving Perjeta, Herceptin, and docetaxel chemotherapy were feeling
tired, abnormal or altered taste, allergic reactions, muscle pain and
*Severe allergic reactions: Some people receiving Perjeta may have severe
allergic reactions, called hypersensitivity reactions or anaphylaxis. This
reaction may be severe, may happen quickly and may affect many areas of
Perjeta has been shown to work only in people with HER2-positive breast
cancer. Patients must have a HER2 test to know if their breast cancer is
HER2-positive before receiving an anti-HER2 treatment, such as Perjeta.
Most Common Side Effects
The most common side effects of Perjeta when given with Herceptin and
docetaxel chemotherapy are:
*Low levels of white blood cells with or without a fever
*Damage to the nerves (numbness, tingling, pain in hands/feet)
Report side effects to the FDA at (800) FDA-1088 or
http://www.fda.gov/medwatch. Patients and caregivers may also report side
effects to Genentech at (888) 835-2555.
Please see Perjeta full Prescribing Information including Most Serious Side
Effect for additional Important Safety Information at http://www.perjeta.com.
About Breast Cancer
Breast cancer is the most common cancer among women worldwide. According to
the American Cancer Society, approximately 235,000 people in the United States
will be diagnosed with breast cancer, and 40,000 will die from the disease in
2013. In HER2-positive breast cancer, increased quantities of the Human
Epidermal growth factor Receptor 2 (HER2) are present on the surface of the
tumor cells. This is known as “HER2 positivity” and affects approximately 25
percent of people with breast cancer. HER2-positive cancer is a particularly
aggressive form of breast cancer.
Founded more than 35 years ago, Genentech is a leading biotechnology company
that discovers, develops, manufactures and commercializes medicines to treat
patients with serious or life-threatening medical conditions. The company, a
member of the Roche Group, has headquarters in South San Francisco,
California. For additional information about the company, please visit
Susan Willson, 650-467-6800
Sonali Padhi, 650-467-0842
Thomas Kudsk Larsen, 650-467-2016
Karl Mahler, 011 41 61 687 8503
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