FDA has approved Pertuzumab [Perjeta] in combination with Trastuzumab [Herceptin] and docetaxel chemotherapy for the treatment of people with HER2-positive metastatic breast cancer

June 13, 2012

June 11, 2012 – The American Food and Drug Administration (FDA) has approved Pertuzumab [Perjeta].  Pertuzumab [Perjeta] is approved in combination with Trastuzumab [Herceptin]  and docetaxel chemotherapy for the treatment of people with HER2-positive metastatic breast cancer (mBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. This approval is based on data from a Phase III study which showed that people with previously untreated HER2-positive mBC who received the combination of Perjeta, Trastuzumab [Herceptin] and docetaxel chemotherapy lived a median of 6.1 months longer without their cancer getting worse (progression-free survival, or PFS) compared to Trastuzumab [Herceptin] plus docetaxel chemotherapy (median PFS 18.5 vs. 12.4 months). The combination of Pertuzumab [Perjeta], Trastuzumab [Herceptin] and chemotherapy is the only regimen to have shown a significant improvement in PFS compared to Trastuzumab [Herceptin] plus chemotherapy in people with previously untreated HER2-positive mBC.

Pertuzumab [Perjeta] is a personalized medicine that targets the HER2 receptor, a protein found in high quantities on the outside of cells in HER2-positive cancers. Pertuzumab [Perjeta] is believed to work in a way that is complementary to Pertuzumab [Perjeta], as the two medicines target different regions on the HER2 receptor. With the approval by the FDA, Genentech, the maker of Pertuzumab [Perjeta] has agreed to post-marketing commitments related to the manufacturing process for Pertuzumab [Perjeta]. These include FDA review of data from the next several productions of the medicine.  “We expect to meet demand for Pertuzumab [Perjeta] following today’s FDA approval. We recently identified a cell growth issue that might affect our future supply of the medicine,” said Patrick Y. Yang, Ph.D., head, Pharma Global Technical Operations. “We take this very seriously and are working with the FDA to ensure a consistent manufacturing process that maintains drug supply for the people who need it.” Pertuzumab [Perjeta] will be available to people in the United States within two weeks. Genentech is committed to helping people who need Pertuzumab [Perjeta]. Genentech Access Solutions is available to provide doctors and patients coverage and reimbursement support, patient assistance and information resources.

Roche has also submitted a Marketing Authorization Application to the European Medicines Agency (EMA) for Pertuzumab [Perjeta] in combination with Trastuzumab [Herceptin] and docetaxel chemotherapy for the treatment of previously untreated HER2-positive mBC or locally recurrent, unresectable (inoperable) breast cancer, in people who have not received previous treatment or whose disease has returned after treatment in the early-stage setting. This application is currently under review by the EMA.

Pertuzumab [Perjeta] Efficacy in HER2-positive mBC

The FDA approval of Pertuzumab [Perjeta] is based on results from CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab), an international, Phase III, randomized, double-blind, placebo-controlled study. The study evaluated the efficacy and safety profile of Pertuzumab [Perjeta] combined with Trastuzumab [Herceptin] and docetaxel chemotherapy compared to Trastuzumab [Herceptin] and chemotherapy plus placebo in 808 people with previously untreated HER2-positive mBC or that had recurred after prior therapy in the adjuvant or neoadjuvant setting. The study showed people who received Pertuzumab [Perjeta] in combination with Trastuzumab [Herceptin] and chemotherapy experienced a 38 percent reduction in the risk of their disease worsening or death compared to people who received Trastuzumab [Herceptin] and chemotherapy plus placebo (HR=0.62; p-value less than 0.0001, according to independent review). The study demonstrated a 6.1 month improvement in median PFS for people who received Pertuzumab [Perjeta] compared to those who received Trastuzumab [Herceptin] and chemotherapy plus placebo (median PFS 18.5 vs. 12.4 months).

In CLEOPATRA, the most common adverse reactions (rate greater than 30 percent) seen with Pertuzumab [Perjeta] in combination with Trastuzumab [Herceptin] and docetaxel were diarrhea, hair loss, low white blood cell count, nausea, fatigue, rash and peripheral neuropathy (numbness, tingling or burning sensation in the arms or legs). The most common Grade 3-4 adverse reactions (rate greater than 2 percent) were low white blood cell count, low white blood cell count with fever, decrease in a certain type of white blood cell, diarrhea, peripheral neuropathy, decrease in red blood cell count, weakness and fatigue.

More about Pertuzumab [Perjeta]

Pertuzumab [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 Pertuzumab [Perjeta] to HER2 may also signal the body’s immune system to destroy the cancer cells. The mechanisms of action of Pertuzumab [Perjeta] and Trastuzumab [Herceptin] are believed to complement each other, as both bind to the HER2 receptor, but to different regions. The combination of Pertuzumab [Perjeta], Trastuzumab [Herceptin] and chemotherapy is thought to provide a more comprehensive blockade of HER signaling pathways.

Pertuzumab [Perjeta] Indication Statement

Pertuzumab [Perjeta]is approved for use along with Trastuzumab [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 breast cancer.

Important Safety Information

  • Pertuzumab [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 Pertuzumab [Perjeta]
  • Because side effects from this treatment are common, it is important to know what side effects may happen and what symptoms patients should watch for
  • 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

Serious Side Effect of Pertuzumab [Perjeta]

Most Serious Side Effect: Receiving Pertuzumab [Perjeta] during pregnancy can result in the death of an unborn baby and birth defects.

  • Birth control should be used while receiving Pertuzumab [Perjeta] and for six months after a patient’s last dose of Pertuzumab [Perjeta]. Patients who are breastfeeding should talk with their doctor about either stopping breastfeeding or stopping Pertuzumab [Perjeta].

Other Possible Side Effects

  • Heart problems: Pertuzumab [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 Pertuzumab [Perjeta]
  • Infusion-related reactions: Pertuzumab [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 Pertuzumab [Perjeta], Trastuzumab [Herceptin], and docetaxel were fatigue, loss of taste, allergic reactions, muscle pain and vomiting
  • Severe allergic reactions: Some people receiving Pertuzumab [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 the body

Most Common Side Effects

The most common side effects of Pertuzumab [Perjeta] when given with Trastuzumab [Herceptin] and docetaxel are diarrhea, hair loss, low levels of white blood cells with or without a fever, upset stomach, fatigue, rash and damage to the nerves (numbness, tingling, pain in hands/feet).

Please see also Pertuzumab [Perjeta] Full Prescribing Information including Most Serious Side Effect for additional Important Safety Information.

 About Trastuzumab [Herceptin]

Trastuzumab [Herceptin] is a personalized medicine designed to specifically block the HER2 protein on the surface of some cancer cells. Based on preclinical studies, this biologic antibody is believed to work by attaching to HER2 receptors to stop signals that make the tumor cells grow and divide, and also by signaling the body’s immune system to destroy the cancer cells.

Trastuzumab [Herceptin] has two approved uses in metastatic breast cancer (mBC):

  • Trastuzumab [Herceptin] in combination with the chemotherapy drug paclitaxel is approved for the first-line treatment of HER2-positive mBC.
  • Trastuzumab [Herceptin] alone is approved for the treatment of HER2-positive mBC in patients who have received one or more chemotherapy regimens for metastatic disease.

Important Safety Information on Trastuzumab [Herceptin]

Trastuzumab [Herceptin] treatment can result in heart problems, including for those patients without symptoms (such as reduced heart function) and those patients with symptoms (such as congestive heart failure). One patient died in an adjuvant breast cancer trial from significantly weakened heart muscle. The risk and seriousness of these heart problems were highest in patients who received both Trastuzumab [Herceptin] and a certain type of chemotherapy (anthracycline).

Before taking the first dose of Trastuzumab [Herceptin] and during treatment, a patient’s doctor should check to see if there are any health conditions that may increase the patient’s chance of having serious heart problems. This includes a review of the patient’s health history and tests to see how well the heart muscle is working. These tests may include an echocardiogram or a multigated acquisition (MUGA) scan. Some early-stage breast cancer patients may also need to have a test done after they have finished taking Trastuzumab [Herceptin] to see how well their heart muscle is working.

Some patients have had serious infusion reactions and lung problems; fatal infusion reactions have been reported. These reactions usually occur during or within 24 hours of receiving Trastuzumab [Herceptin].

The patient’s doctor may need to completely stop Trastuzumab [Herceptin] treatment if the patient has a severe allergic reaction, swelling, lung problems, inflammation of the lung or severe shortness of breath.

Trastuzumab [Herceptin] can cause harm to the fetus (unborn baby), and in some cases death to the fetus, when taken by a pregnant woman. Women who could become pregnant need to use effective birth control methods during Trastuzumab [Herceptin] treatment and for at least six months after treatment with Trastuzumab [Herceptin]. Nursing mothers treated with Trastuzumab [Herceptin] should discontinue nursing or discontinue Trastuzumab [Herceptin].

Worsening of low white blood cell counts associated with chemotherapy has also occurred.

Patients must have a HER2 test to determine if their breast cancer is HER2-positive before using Trastuzumab [Herceptin], as benefit has only been shown in patients who are HER2-positive.

The most common side effects associated with Trastuzumab [Herceptin] in patients with breast cancer are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cells and muscle pain.

Because everyone is different, it is not possible to predict what side effects any one patient will have. Patients with questions or concerns about side effects should talk to their doctor.

Patients should read the Trastuzumab [Herceptin] full Prescribing Information including Boxed Warnings.

About Breast Cancer

Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 229,000 people will be diagnosed with breast cancer, and 40,000 will die from the disease in 2012. 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.

Patients are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088.


New Breast Cancer HER2 Diagnostic Tests Approved by FDA

June 13, 2012
June 12, 2012 — Two diagnostic tests to identify HER2-positive breast cancer have been approved by the US Food and Drug Administration (FDA) for use as companion diagnostics for the new targeted therapy Pertuzumab [Perjeta].
 
The tests — HercepTest and HER2 FISH pharmDx Kit — are both manufactured by Dako in Glostrup, Denmark. The tests serve as diagnostic tools to identify patients with HER2-positive metastatic breast cancer who might be eligible for treatment with HER2-positive targeted therapies. The latest of these —Pertuzumab [Perjeta]— was approved  just days ago by the American Food and Drug Administration (FDA) for use in combination with Trastuzumab [Herceptin] and chemotherapy in patients with HER2-positivemetastatic breast cancer who have not been treated with either trastuzumab or chemotherapy.
 
“The role of HER2 in diagnosis and clinical decision making continues to evolve with the recent approval of Pertuzumab [Perjeta]”, said David Hicks, MD, director of surgical pathology at the University of Rochester Medical Center in New York. “It is clear that optimal patient care depends now more than ever on the accurate, reliable, and reproducible assessment of HER2 status for the full benefit of pertuzumab to be derived by the appropriate patient population,” he noted in a Dako press release. Dako reported that it had been collaborating with Genentech on a parallel FDA approval process for the 2 tests and the new drug.

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