Perjeta Treatment of HER2 positive Breast Cancer

FDA Approves Perjecta for Adjuvant Treatment of HER2-positive Breast Cancer

On December 20, 2017, the Food and Drug Administration granted regular approval to Perjeta (pertuzumab) for use in combination with Herceptin (trastuzumab) and chemotherapy as adjuvant treatment of patients with HER2-positive early stage breast cancer at high risk of recurrence.

Perjeta Approved for the Treatment of Advanced HER2 Breast Cancer

The U.S. Food and Drug Administration (FDA) has approved Perjeta® (pertuzumab) for the treatment of HER2-positive, metastatic breast cancer. The drug is approved for use in combination with Herceptin® (trastuzumab) and docetaxel chemotherapy in patients who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

Breast cancer is the second leading cause of cancer-related death among women. This year an estimated 226,870 women will be diagnosed with breast cancer, and 39,510 will die from the disease. Approximately 20-25 percent of breast cancers overexpress (make too much of) the human epidermal growth factor receptor 2 (HER2), which is part of a biological pathway involved in growth and spread of cancer cells.

HER2-targeted therapies such as Herceptin have dramatically improved outcomes for women with HER2-positive breast cancer, but researchers continue to explore new approaches to treatment.

Perjeta is given intravenously and targets a different part of the HER2 protein than Herceptin. Since the two drugs target different regions of HER2, they are believed to work in a way that is complementary to each other.

The approval was based on data from an international, phase III, randomized, double-blind, placebo-controlled study that involved 808 patients with HER2-positive metastatic breast cancer. Patients were randomly assigned to receive Perteja/Herceptin/docetaxel or Herceptin/docetaxel/placebo. The results indicated that patients who received the combination of Perjeta/Herceptin/docetaxel lived longer without their cancer getting worse—median progression-free survival (PFS) in the Perjeta group was 18.5 months compared to 12.4 months in the placebo group.

The most common adverse events in patients receiving Perteja in combination with Herceptin and docetaxel were diarrhea, hair loss, low white blood cell count, nausea, fatigue, rash, and peripheral neuropathy (numbness or tingling in the extremities).

Perteja will include a Boxed Warning, which will alert patients and physicians to the potential risk of death or severe defects to a fetus. It is imperative to confirm a negative pregnancy status prior to starting treatment with Perjeta.

The drug was reviewed under the agency’s priority review program, which allows an expedited six-month review of drugs that may offer major advances in treatment.

Reference:

FDA approves Perjeta for type of late-stage breast cancer [FDA News Release]. U.S. Food and Drug Administration website. Available at:

About Perjeta

Breast cancer is the second leading cause of cancer-related death among women. This year an estimated 226,870 women will be diagnosed with breast cancer, and 39,510 will die from the disease. Approximately 20-25 percent of breast cancers overexpress (make too much of) the human epidermal growth factor receptor 2 (HER2), which is part of a biological pathway involved in growth and spread of cancer cells.

Perjeta is given intravenously and targets the HER2 protein. It was approved in 2012 for the treatment of patients with advanced or late-stage (metastatic) HER2-positive breast cancer. Its 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 Herceptin® and other chemotherapy prior to surgery and, depending upon the treatment regimen used, may be followed by chemotherapy after surgery.

Approval of Perjeta was based on data from the APHINITY multicenter, clinical trial performed in 4804 patients with HER2-positive early stage breast cancer who had their primary tumor removed by surgery. Patients were then treated with either Perjeta or placebo, in combination with adjuvant both Herceptin and chemotherapy.

In the current trial patients were followed for evidence of invasive disease-free survival (IDFS) – defined as the time to first occurrence of cancer recurrence, development of a contralateral invasive breast cancer, or death from any cause.

After a median follow-up of 45.4 months, the proportion of IDFS events was 7.1% for Perjeta caompared to 8.7% (n=210) for those receiving placebo. High-risk patients included patients such as those with hormone receptor negative or those with node positive breast cancer. The proportion of IDFS events in patients with hormone receptor negative disease was 8.2% for Perjeta compared to 10.6% for placebo. The proportion of IDFS events for patients with node positive disease was 9.2% for Perjeta and 12.1% for placebo. Overall survival data are not yet mature.

Perjeta Approved for Neoadjuvant Treatment of Early Stage HER2-Positive Breast Cancer

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Perjeta® (pertuzumab) for the neoadjuvant treatment of early stage breast cancer before surgery. This is the first drug approved for the neoadjuvant treatment of breast cancer.

Breast cancer is the second leading cause of cancer-related death among women. This year an estimated 226,870 women will be diagnosed with breast cancer, and 39,510 will die from the disease. Approximately 20-25 percent of breast cancers overexpress (make too much of) the human epidermal growth factor receptor 2 (HER2), which is part of a biological pathway involved in growth and spread of cancer cells.

Perjeta is given intravenously and targets the HER2 protein. It was approved in 2012 for the treatment of patients with advanced or late-stage (metastatic) HER2-positive breast cancer. Its 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 Herceptin® (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 Herceptin to complete one year of treatment.

The approval was based on data from a study that included 417 patients who were randomly assigned to receive one of four neoadjuvant treatment regimens: Hercpetin plus docetaxel; Perjeta plus Herceptin and docetaxel; Perjeta plus Herceptin; or Perjeta plus docetaxel. About 39 percent of patients who received Perjeta plus Herceptin and docetaxel achieved pathologic complete response (pCR) compared with about 21 percent who received Herceptin plus docetaxel.

The most common side effects reported in participants receiving Perjeta plus Herceptin 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.

A confirmatory trial is being conducted in patients 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.

Reference:

FDA approves Perjeta for neoadjuvant breast cancer treatment. [FDA Announcement]. U.S. Food and Drug Administration website.

Impressive Survival Gains with New First-Line Therapy for HER2-Positive Metastatic Breast Cancer

According to recent findings, the combination of targeted agents Herceptin (trastuzumab) and Perjeta (perjeta) significantly improves survival for patients with HER2-positive metastatic breast cancer when added to chemotherapy. This data was presented at the 2014 European Society for Medical Oncology (ESMO) Congress in Madrid, Spain, September 26–30.[1]

HER2 is a protein involved in normal cell growth. Approximately 20–25% of breast cancers overexpress (make too much of) the HER2 protein, and this over-expression contributes to cancer cell growth and survival. HER2-targeted therapies such as Herceptin have dramatically improved outcomes for women with HER2-positive breast cancer, but researchers continue to explore new approaches to treatment.

To evaluate the combination of Herceptin and Perjeta plus chemotherapy (with Taxotere® [docetaxel]) as first-line therapy for patients with HER2-postive metastatic breast cancer, researchers have conducted a Phase III clinical study called the CLEOPATRA trial. This trial included 808 patients, who were assigned to receive Herceptin and Perjeta plus chemotherapy or Herceptin-only plus chemotherapy.

In early follow-up, the combination of Herceptin and Perjeta plus chemotherapy appeared promising: patients in this group experienced improved progression-free and overall survival, and overall survival continued to improved at the next follow-up.

Now that final overall survival results are available, the combination of Herceptin and Perjeta plus chemotherapy still appears more effective than Herceptin-only plus chemotherapy. At last follow-up, median overall survival was over 15 months longer in the Perjeta group: over 56 months versus just over 40 months for the Herpceptin-only group. In addition, the researchers found no previously unknown safety concerns for this treatment combination.

“The results of the study are really outstanding,” said Giuseppe Curigliano, DM, Director of the Division of Experimental Therapeutics in Milan, Italy. He called the more than 56-month median overall survival for Herceptin and Perjeta plus chemotherapy “unprecedented” in the treatment of HER2-positive metastatic breast cancer and added, “The CLEOPATRA trial changes clinical practice. We now have a new standard of care for patients with metastatic HER2-positive breast cancer.”[2]

References:

[1] Swain S, Kim S,Cortes J, et al. 350O_PR – Final overall survival (OS) analysis from the CLEOPATRA study of first-line (1L) pertuzumab (Ptz), trastuzumab (T), and docetaxel (D) in patients (pts) with HER2-positive metastatic breast cancer (MBC). European Society for Medical Oncology (ESMO) Congress 2014: Abstract 350O_PR. Presented September 28, 2014.

[2]CLEOPATRA Trial Changes Standard Therapy for Metastatic HER2 Positive Breast Cancer [press release]. European Society for Medical Oncology (ESMO) Congress 2014. Available at: . Accessed October 4, 2014.

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