Fda has approved perjeta for neoadjuvant use!!

[carolanno]

Don't know if anyone has seen or posted this yet, but check it out! Because of Perjeta's great performance when added to the Herceptin/chemo regimen to shrink tumors prior to surgery, it has won accelerated approval to be used in early stage breast cancer. It is the first breast cancer drug they've approved for this use. Instead of waiting until it's metastasized and then treating w/Perjeta, we may actually prevent it from happening. Hopefully, women won't be denied coverage any longer for this potentially life saving drug.

['lizbeth]

FDA NEWS RELEASE

For Immediate Release: Sept. 30, 2013
Media Inquiries: Stephanie Yao, 301-796-0394, stephanie.yao@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
FDA approves Perjeta for neoadjuvant breast cancer treatment
First drug approved for use in preoperative breast cancer
The U.S. Food and Drug Administration today granted accelerated approval to Perjeta (pertuzumab) as part of a complete treatment regimen for patients with early stage breast cancer before surgery (neoadjuvant setting). Perjeta is the first FDA-approved drug for the neoadjuvant treatment of breast cancer.
Perjeta was approved in 2012 for the treatment of patients with advanced or late-stage (metastatic) HER2-positive breast cancer. HER2-positive breast cancers have increased amounts of the HER2 protein that contributes to cancer cell growth and survival.
Perjeta’s new use is intended for patients with HER2-positive, locally advanced, inflammatory or early stage breast cancer (tumor greater than 2 cm in diameter or with positive lymph nodes) who are at high risk of having their cancer return or spread (metastasize) or of dying from the disease. It is to be used in combination with trastuzumab and other chemotherapy prior to surgery and, depending upon the treatment regimen used, may be followed by chemotherapy after surgery. Following surgery, patients should continue to receive trastuzumab to complete one year of treatment.
“We are seeing a significant shift in the treatment paradigm for early stage breast cancer,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “By making effective therapies available to high-risk patients in the earliest disease setting, we may delay or prevent cancer recurrences.’’
In May 2012, the FDA issued a draft guidance about the use of pathologic complete response (pCR), defined as the absence of invasive cancer in the breast and lymph nodes, as an endpoint to support accelerated approval of a drug for neoadjuvant treatment of high-risk, early stage breast cancer. Under the FDA’s accelerated approval program, patients are provided access to promising drugs to treat serious or life-threatening conditions while confirmatory clinical trials are conducted.
Perjeta’s accelerated approval for neoadjuvant treatment is based on a study designed to measure pCR. In the study, 417 participants were randomly assigned to receive one of four neoadjuvant treatment regimens: trastuzumab plus docetaxel, Perjeta plus trastuzumab and docetaxel, Perjeta plus trastuzumab or Perjeta plus docetaxel. About 39 percent of participants who received Perjeta plus trastuzumab and docetaxel achieved pCR, compared to about 21 percent who received trastuzumab plus docetaxel.
The confirmatory trial for this accelerated approval is being conducted in participants with HER2-positive breast cancer who had prior breast cancer surgery and are at high risk of having their cancer return. More than 4,800 participants are enrolled in this trial, which will provide further data on efficacy, safety and long-term outcomes. Results are expected in 2016.
The most common side effects reported in participants receiving Perjeta plus trastuzumab and docetaxel were hair loss, diarrhea, nausea and a decrease in infection-fighting white blood cells. Other significant side effects included decreased cardiac function, infusion-related reactions, hypersensitivity reactions and anaphylaxis.
The FDA reviewed Perjeta’s use for neoadjuvant treatment under the agency’s priority review program, which provides for an expedited review of drugs that may offer major advances in treatment.
Breast cancer is the second leading cause of cancer-related death among women. An estimated 232,340 women will be diagnosed with breast cancer, and 39,620 will die from the disease in 2013, according to the National Cancer Institute. Almost 20 percent of breast cancers have increased amounts of the HER2 protein.
Perjeta is marketed by Genentech, a member of the Roche Group, based in South San Francisco, Calif.
For more information:
FDA: Office of Hematology and Oncology Products
FDA: Approved Drugs: Questions and Answers
NCI: Breast Cancer
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

['lizbeth]

Monday, Sep 30, 2013
FDA Grants Genentech’s Perjeta Accelerated Approval for Use Before Surgery in People With HER2-Positive Early Stage Breast Cancer

• The Perjeta regimen is the first treatment approved under a new FDA pathway for neoadjuvant use in breast cancer
• This new approval pathway makes Perjeta available to people with high-risk, early stage breast cancer more quickly than is possible with traditional approvals

South San Francisco, Calif. -- September 30, 2013 --
SOUTH SAN FRANCISCO, Calif. – September 30, 2013 – Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) granted accelerated approval of a Perjeta® (pertuzumab) regimen for neoadjuvant treatment (use before surgery) in people with high-risk, HER2-positive early stage breast cancer. This approval is based primarily on data from a Phase II study showing that nearly 40 percent of people receiving the combination of Perjeta, Herceptin® (trastuzumab) and docetaxel chemotherapy had no evidence of tumor tissue detectable at the time of surgery (known as a pathological complete response, or pCR). The Perjeta regimen is the first neoadjuvant breast cancer treatment approved by the FDA and also the first to be approved based on pCR data.
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. Treating people with breast cancer early, before the cancer has spread, may offer the best chance of preventing the disease from returning.
“A new approval pathway has made Perjeta available to people with HER2-positive early breast cancer several years earlier than previously possible,” said Hal Barron, M.D., chief medical officer and head, Global Product Development. “Together with the FDA, we’ve charted new territory. We look forward to working with health authorities around the world to explore additional ways to bring promising medicines to patients more quickly.”
This new neoadjuvant indication for Perjeta is for use prior to surgery in combination with Herceptin and docetaxel chemotherapy in people with HER2-positive, locally advanced, inflammatory, or early stage (tumor is greater than two centimeters in diameter or node positive) breast cancer. Perjeta should be used as part of a complete treatment regimen for early stage breast cancer. This use of Perjeta is based on an improvement in the percentage of people who had no evidence of cancer in the breast or lymph nodes at the time of surgery. Currently, no data have shown whether or not treatment with Perjeta prior to surgery improves survival. The safety of Perjeta as part of a doxorubicin (chemotherapy)-containing regimen has not been established. The safety of Perjeta administered for greater than six cycles for early stage breast cancer has not been established.
The Perjeta neoadjuvant indication was granted under the FDA’s accelerated approval program, which allows conditional approval of a medicine for a life-threatening disease based on early evidence suggesting clinical benefit. The approval is based on results from the NEOSPHERE study, a Phase II study of Perjeta in high-risk, HER2-positive early stage breast cancer. Additional data from the TRYPHAENA study, as well as longer-term safety data from the Phase III CLEOPATRA study of Perjeta in HER2-positive metastatic breast cancer, were also submitted in support of the approval. TRYPHAENA is a Phase II study of Perjeta in HER2-positive early stage breast cancer designed primarily to assess cardiac safety.
A full review of data from the ongoing Phase III APHINITY study will be required for the accelerated approval to be converted to a full approval. APHINITY compares Perjeta, Herceptin and chemotherapy with Herceptin and chemotherapy for adjuvant (post-surgery) treatment in people with HER2-positive early stage breast cancer. Data from APHINITY are expected in 2016.
Roche is discussing the option of submitting Perjeta in the neoadjuvant setting to regulatory authorities in other countries around the world. 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 body) or locally recurrent, unresectable (inoperable) breast cancer who have not received previous anti-HER2 therapy or chemotherapy for their metastatic disease.
Perjeta Data in HER2-positive Early Stage Breast Cancer
NEOSPHERE Study
The NEOSPHERE study (Neoadjuvant Study of Pertuzumab and Herceptin 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. 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), leukopenia (decrease in overall white blood cells, 4.7 percent) and diarrhea (5.6 percent).

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 alone.
• The most common severe (Grade 3 or higher) 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), febrile neutropenia (9.3 percent), diarrhea (5.3 percent) and left ventricular dysfunction (4.0 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 percent

About Perjeta
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.
Perjeta Indication Statements
Perjeta is approved for use in combination with Herceptin and docetaxel chemotherapy in people who have 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.
Perjeta is approved for use prior to surgery in combination with Herceptin and docetaxel chemotherapy in people with HER2-positive, locally advanced, inflammatory, or early stage (tumor is greater than two centimeters in diameter or node positive) breast cancer. Perjeta should be used as part of a complete treatment regimen for early stage breast cancer. This use of Perjeta is based on an improvement in the percentage of people who had no evidence of cancer in the breast or lymph nodes at the time of surgery. Currently, no data have shown whether or not treatment with Perjeta prior to surgery improves survival. The safety of Perjeta as part of a doxorubicin (chemotherapy)-containing regimen has not been established. The safety of Perjeta administered for greater than six cycles for early stage breast cancer has not been established.
Important Safety Information
Most Serious Side Effects of Perjeta
Perjeta may cause 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 Perjeta.

Receiving Perjeta during pregnancy can result in the death of an unborn baby and birth defects.

• Patients who think they may be pregnant should contact their healthcare provider immediately.
• If patients are exposed to Perjeta during pregnancy, they are encouraged to enroll in the MotHER Pregnancy Registry by contacting (800) 690-6720.

Perjeta should not be used in patients who are allergic to pertuzumab or to any of the ingredients in Perjeta.
Other Possible Serious Side Effects

• 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 vomiting
• 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 the body

Perjeta has only been shown to work in people with HER2-positive breast cancer.
Most Common Side Effects
The most common side effects of Perjeta when given with Herceptin and docetaxel chemotherapy for treatment of breast cancer that has spread to other parts of the body (metastatic) are:

• Diarrhea
• Hair loss
• Low levels of white blood cells with or without a fever
• Nausea
• Feeling tired
• Rash
• Damage to the nerves (numbness, tingling, pain in hands/feet)

The most common side effects of Perjeta when given with Herceptin and docetaxel chemotherapy as part of an early stage breast cancer regimen before surgery are:

• Hair loss
• Diarrhea
• Nausea
• Low levels of white blood cells with or without a fever

The most common side effects of Perjeta when given with Herceptin and docetaxel chemotherapy following three cycles of epirubicin, cyclophosphamide and fluorouracil as part of an early stage breast cancer regimen before surgery are:

• Feeling tired
• Hair loss
• Diarrhea
• Nausea
• Vomiting
• Low levels of white blood cells with or without a fever

The most common side effects of Perjeta when given with Herceptin, docetaxel chemotherapy and carboplatin chemotherapy as part of an early stage breast cancer regimen before surgery are:

• Feeling tired
• Hair loss
• Diarrhea
• Nausea
• Vomiting
• Low levels of white blood cells with or without a fever
• Low platelet count
• Low levels of red blood cells

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 Effects 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.
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.
About Genentech Access Solutions
Genentech is committed to people having access to our medicines. Genentech Access Solutions is a team of more than 350 Genentech employees who help those who need our medicines. Our knowledgeable and experienced specialists can help patients and medical practices navigate the access and reimbursement process and provide assistance to eligible patients in the United States who do not have insurance coverage or who cannot afford their out-of-pocket co-pay costs. For more information, please visit http://www.Genentech-Access.com.
About Genentech
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 http://www.gene.com.

[phil]

I am excited that this drug will be available at the outset of dx and tx for her2 bc. But it is Still Denied to Stage IV's . Thanks to this Slow , Piece - meal FDA approval process with Perjeta . I know for a fact that Ins. co's are denying Stage IV appr. for Perjeta. BC/BS of the NW for one. Based on it not being fda approved for Stage IV. How many more yrs ??
maybe I'm just suspiscious, but PCR is one of FDA head Dr. Pazdours' " pet stats . he has written on it. he is the architect of the FDA slow -down of approvals, , starting in 2009 . he has championed replacing time to progr., TTP, and progr.- free survival, PFS with overall survival stats , OS. this slows down approval time , even as the drugs get better , and many are genetic, with fewer s/e.
OS , PCR leave a bad taste in my mouth , I think of how his focus on OS has actually led to LESS SURVIVAL. in the cases of T DM-1 and pertuzumab, so far.

[LeahM]

Wishing it would be approved as for Stage 4 too. I wanted this so bad when first diagnosed but couldn't get it. Now, 3 months off Herceptin I can't get it in the future. It's time for a change.

['lizbeth]

FDA approves Perjeta for type of late-stage breast cancer
The U.S. Food and Drug Administration today approved Perjeta (pertuzumab), a new anti-HER2 therapy, to treat patients with HER2-positive late-stage (metastatic) breast cancer.
Intended for patients who have not received prior treatment for metastatic breast cancer with an anti-HER2 therapy or chemotherapy, Perjeta is combined with trastuzumab, another anti-HER2 therapy, and docetaxel, a type of chemotherapy.

@Leah - I think you would qualify. You haven't received any treatment other than for Stage I/II breast cancer, correct?
Knock on wood - that you will never, ever need Perjeta!

I agree with Phil about how piecemeal the approvals are becoming. Why Perjeta only for firstline MBC treatment? This is so frustrating.

I checked Genentech's pipeline for phase III trials for MBC.
I see there is an ongoing trial for Perjeta for 2nd line MBC, and TDM1 for 1st and 3rd line MBC.

The system is the system. I try and post all the clinical trials I come across. The way the system is - we need to work to get full enrollment in the trials as quickly as possible.

With Pcr as an outcome, FastTrack could open up the treatment options for early breast cancer in rapid succession. Hopefully more & more options will enter into the pipeline since the cost of these trials will be dropping significantly. Having income years earlier than typical must be a huge boost to Roche. I hope this helps Genentech move more early breast cancer targeted therapies into the pipeline.

I remember when I was searching for clinical trials in 2007, I felt left out because it seemed that I had to wait until the clinical trial for MBC ended, and then the early breast cancer trial had to start and end. I wondered why the trials couldn't start at the same time. Things have really changed in the last 6 years. This fast track on neoadjuvant studies is quite a shift for the FDA.

So what change would help the stage IV/MBC patients the most? I dislike the system of trying one toxic chemo, then another in the hopes that it will work. Isn't there a company in Greece that can extract CTCs and then run tests (similar to Rational Therapeutics solid tumor cell death end points) to determine which treatments are the most effective?

That is my wish, to use the cancer cells as the test dummy for treatments, and not the MBC patient. The current system truly makes them suffer, and it need to change.

[LeahM]

Thanks 'lizbeth for clearing that up for me. I was under the impression that if you had had a targeted therapy med before for HER2+ then you couldn't get Perjeta. Good for me to know it is available. I will ask my BS about this again as I was under the impression from a recent seminar I went to that I wasn't a candidate for it if (God forbid) I morph into Stage 4.

I will look for the Greek company, I agree that using MBC patients as test dummies isn't a very good idea.

so much to think about. thank you

[LeahM]

Ok wait. Just so I'm clear on this. If Herceptin fails me, a person with early stage BC then I can get Perjeta, but if Herceptin fails a Stage 4 then that person can't get Perjeta?

[jacqueline1102]

Hi all,

Just wanted you to know that I am stage IV and have been receiving Herceptin and Perjeta since August 1, 2012. So far so good. I don't understand why some/many women are not getting this drug. In my treatment center, there is another woman who is Stage IV and she, too, received Perjeta.

Take care,

Jackie

[KDR]

Wondering, are you at a smaller facility? I have heard it (had been) much easier to gain access at one vs. a larger place.

['lizbeth]

Leah,

I think some of the ladies are receiving it off label. After all the standard of care guidelines . . . are just guidelines.

I think some doctors invoke Parlay . . .

Elizabeth: Wait! You have to take me to shore. According to the Code of the Order of the Brethren...
Barbossa: First, your return to shore was not part of our negotiations nor our agreement so I must do nothing. And secondly, you must be a pirate for the pirate's code to apply and you're not. And thirdly, the code is more what you'd call "guidelines" than actual rules. Welcome aboard the Black Pearl, Miss Turner!