Breast Cancer Treatment with the Herceptin and Perjeta Targeted Drug Regimen

How Do Herceptin and Perjeta Work?

Herceptin (active ingredient trastuzumab) and Perjeta (active ingredient pertuzumab) are targeted drugs, each designed to kill cancer cells or slow their growth by stopping their ability to grow and multiply.

Purpose of Treatment

The Herceptin + Perjeta regimen is used in breast cancers with high levels of the HER2 receptor on the cell surface, therefore called HER2-positive breast cancers, for 3 purposes:

1. Neoadjuvant treatment: To reduce tumor size before surgery, improve surgical success and thus reduce the likelihood of postoperative recurrence,
2. Adjuvant treatment: To destroy cancer cells that may remain in the body after surgery performed as the initial treatment,
3. Palliative treatment: Stage 4 (metastatic) breast cancer is treated to regress and control the disease, extend survival and reduce disease-related symptoms.

Herceptinis started with chemotherapy in early-stage disease in our country, as worldwide, to reduce recurrence risk and is used for 1 year. In locally advanced patients, it is used with chemotherapy to regress the disease and make surgery possible. After surgery, the one-year course is completed for preventive purposes.

Perjetafirst received FDA approval in metastatic HER2-positive breast cancer with Herceptin and the chemotherapy drug docetaxel in 2012. This use was approved in our country only in July 2016. In 2013, it received FDA approval for neoadjuvant (tumor-shrinking, preparatory to surgery) treatment of locally advanced HER2-positive breast cancer, but this use has not yet been approved in our country.

What Does HER2-Positive Mean?

Human Epidermal Growth Factor Receptor 2 (HER2) is a receptor mediating cellular growth factors. In HER2-positive breast tumors, cancer cells overproduce this receptor (overexpression), making the cancer behave more aggressively. Before new-generation targeted drugs against the HER2 receptor were developed, HER2 positivity was associated with poorer outcomes and more frequent recurrence. Approximately %20 of breast cancers are HER2-positive.

Administration, Dose and Schedule

• Trastuzumab (Herceptin) 8mg/kg, the loading dose for the first cycle, is administered on day 1 intravenously (intraVenous = İ.V.), slowly over 90 minutes during the first cycle. In the second cycle, trastuzumab 6mg/kg (maintenance dose) is given over 60 minutes. From the third cycle onward, if tolerated, trastuzumab 6mg/kg (maintenance dose) is administered over 30 minutes. Administering medication intravenously over a specified time in this way is called an infusion .
• Pertuzumab (Perjeta) 840 mg, the first-cycle loading dose, is given on day 1 intravenously over 60 minutes in the first cycle, followed by observation for 30 to 60 minutes. From the second cycle onward, pertuzumab 420mg (maintenance dose) is given over 30 minutes, followed by observation for 30 to 60 minutes.

Estimated Total Duration of Herceptin + Perjeta Treatment

• The first cycle of Herceptin + Perjeta, including preparatory medications, may take approximately 2.5 hours.
• Subsequent cycles may take approximately 1 hour.
• Infusion times are based on clinical research but may vary with physician preference or the patient’s tolerance. Premedications and fluid support may add more time.
• Herceptin + Perjeta treatment is generally given in outpatient chemotherapy units, with patients returning home afterward.
• Herceptin + Perjeta treatment is repeated every 21 days (3 weeks) . This interval is known as 1 cycle. Treatment continues for the period the physician considers appropriate, depending on its benefit.

Turkish Authorization and SGK Reimbursement Status 

Trastuzumab was authorized on 01.08.2003 and pertuzumab on 16.02.2016 by Roche Müstahzarları Sanayi Anonim Şirketi.

SGK Reimbursement Status

Pertuzumab

• In patients without previous systemic chemotherapy or trastuzumab for metastatic disease, with an ECOG performance score of 0-1, HER-2 immunohistochemistry +3 or FISH/CISH/SISH (+), and visceral metastases, it may be used in first-line metastatic breast cancer with trastuzumab and docetaxel chemotherapy until progression.
• Pertuzumab is not used in patients who previously received adjuvant or neoadjuvant trastuzumab for early-stage breast cancer and subsequently relapsed. In patients progressing during pertuzumab, it cannot be continued again as monotherapy or part of combination treatment.
• If docetaxel chemotherapy is discontinued because of toxicity, treatment may continue with trastuzumab and pertuzumab.

Trastuzumab

• In patients with HER-2 immunohistochemistry +3 or FISH/CISH/SISH (+), for metastatic breast cancer, it is prescribed by medical oncologists based on a medical board report including a medical oncology specialist and specifying this status. Treatment is stopped if progression occurs while using trastuzumab.
• In patients with HER-2 immunohistochemistry +3 or FISH/CISH/SISH (+), the treatment duration for early-stage breast cancer is 9 weeks. Where completion to 52 weeks is contemplated under the Ministry of Health’s drug regulation, after 9 weeks it is prescribed by these physicians with a 3-month medical board report including at least one medical oncology specialist and echocardiographic assessment. Total treatment duration cannot exceed 52 weeks.
• In patients with metastatic gastric or gastroesophageal junction adenocarcinoma who have not received chemotherapy and whose Her-2 neu positivity is demonstrated both by immunohistochemistry +2/+3 and by positive FISH/CISH/SISH, it may be combined with platinum and capecitabine or platinum and 5-fluorouracil chemotherapy. Treatment is stopped upon progression. It is prescribed by medical oncologists with a medical board report including a medical oncology specialist.

Without Additional TİTCK Approval;

• Advanced endometrial cancer (Trastuzumab): in Her2-positive serous subtype, from the 2nd line onward in platinum-sensitive disease, use with carboplatin and paclitaxel is appropriate. HER2 positivity must be demonstrated by both IHC and FISH.
• Stage IV colorectal cancer (Trastuzumab+ Pertuzumab): in Her2-positive disease (ihk3+ or fısh+) with wild-type ras, use from the 2nd line onward is appropriate.
• Stage IV colorectal cancer (Trastuzumab+ Lapatinib): in Her2-positive disease (ihk3+ or fısh+) with wild-type ras, use from the 2nd line onward is appropriate.
• Tumors with nonsecretory histology (mucoepidermoid, salivary gland carcinoma, adenocarcinoma NOS): (head-neck, Trastuzumab) in Her2-positive (ihk+3 or fısh +) metastatic patients progressing after one chemotherapy line, use with chemotherapy or as monotherapy is appropriate.

Herceptin 150 mg vial: 9.523.85 TL

Perjeta 420 mg vial: 61.720.83 TL

Herceptin and Perjeta Side Effects

In multidrug regimens, each drug has its own side effects. Side effects potentially arising from these two drugs together have been estimated from clinical trial results. Targeted drugs cause far fewer side effects than chemotherapies. The most common side effects associated with Herceptin + Perjeta in clinical trials are:

• Reduced heart function, which tends to occur in older patients and is generally rare
• Skin rashes
• Allergic reaction

Monitoring

How Often Is Monitoring Needed?

The Herceptin + Perjeta combination is not expected to lower blood counts. However, if given with chemotherapy, as it often is with taxanes, blood tests before treatment are recommended. Required tests are a complete blood count and comprehensive metabolic panel (biochemistry). Other blood tests may be added as the physician recommends.

How Often Is Imaging (Radiological Examination) Needed?

Heart ultrasound, echocardiography, is typically performed before initial treatment and then periodically to monitor heart function.

- If used before surgery for tumor shrinkage (neoadjuvant treatment), your oncologist may assess response every 2-4 cycles using imaging such as breast ultrasound, computed tomography or PET-CT).

- If given after surgery for prevention (adjuvant treatment), imaging is not performed during treatment except in special situations.

- If used palliatively for metastatic disease, imaging may likewise be planned every 2-4 cycles to assess response.

How Do Blood Test or Imaging Results Affect Treatment?

Depending on the results, your doctor may continue Herceptin + Perjeta as planned, change the dose or change treatment.

Precautions

• Plan your time allowing for extra time at the infusion center if a reaction to either Herceptin + Perjeta occurs. Most infusion centers start this treatment early in the morning to leave extra time during the day for unexpected delays.
• Preoperative Herceptin + Perjeta use is known to delay surgical wound healing. This should be considered particularly when breast reconstruction by plastic surgeons is planned alongside breast cancer surgery. When Herceptin + Perjeta are combined, reconstruction should be postponed rather than performed at the same time as breast cancer surgery.
• Your oncology pharmacist should check for interactions between medications.

Individual Drug Label Information

Herceptin (Trastuzumab)

• Herceptin is an intravenous infusion.
• Heart function must be checked before starting trastuzumab and every 3 months during treatment. If the heart’s pumping ability falls, treatment may need to be interrupted to allow recovery. Various medications may also be started to help improve heart function.
• Rarely, lung side effects (toxicity) may occur. This risk is higher in people with existing lung disease.
• It may cause serious birth defects when given to pregnant women. Use suitable birth control during trastuzumab treatment and notify your doctor if you become pregnant.

General Herceptin (Trastuzumab) Side Effects

• It may cause infusion reactions, usually only during the first cycle. If these occur, you should receive acetaminophen (such as Parol, Minoset or Vermidon), diphenhydramine (Avil, etc.) and a corticosteroid before all subsequent cycles.
• It may cause skin peeling.
• It may cause cough, runny nose and shortness of breath.

Perjeta (Pertuzumab)

• Perjeta is an intravenous infusion.
• Heart function must be checked before starting pertuzumab and every 3 months during treatment. If the heart’s pumping ability falls, treatment may need to be interrupted to allow recovery. Various medications may also be started to help improve heart function.
• It may cause serious birth defects when given to pregnant women. Use suitable birth control during trastuzumab treatment and notify your doctor if you become pregnant.

General Perjeta (Pertuzumab) Side Effects

• It may cause infusion reactions, usually only during the first cycle. If these occur, you should receive acetaminophen, diphenhydramine and a corticosteroid before all subsequent cycles.
• Patients are typically observed for 30-60 minutes after Perjeta infusion. If another drug is given alongside Perjeta, treatment generally starts with Perjeta, and observation continues while you receive the other drug.
• It frequently causes diarrhea. This can be controlled with antidiarrheal drugs such as Lopermid or Lomotil.
• It may cause skin rashes.

What Is the Mechanism of Herceptin and Perjeta?

Trastuzumab (Herceptin) and pertuzumab (Perjeta) are monoclonal antibodies that act on HER2 receptors, important components of cell growth signaling pathways, preventing growth factors from binding. Cancer cells bound by monoclonal antibodies both proliferate more slowly and become visible to our immune cells. Thus, anti-HER2 treatments also belong to a cancer immunotherapy group. Herceptin prevents growth factors from binding to the HER2 receptor; Perjeta prevents the HER2 receptor from binding to similar receptors and becoming activated.

- You may be interested in: We are now stronger in targeted drug treatment for breast cancer