Perjeta® (pertuzumab) in HER2-Positive Metastatic Breast Cancer

In June 2012, the U.S. Food and Drug Administration (FDA) approved Perjeta® (pertuzumab)* in combination with Herceptin® (trastuzumab) and docetaxel chemotherapy for people with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic breast cancer.¹

The combination of Perjeta, trastuzumab and docetaxel chemotherapy was the only regimen that has been shown to significantly improve the time people with previously untreated HER2-positive metastatic breast cancer lived without their disease getting worse (median progression-free survival, or PFS, 18.5 vs. 12.4 months; 6.1 months improvement) compared to trastuzumab and docetaxel chemotherapy.^{1, 2}

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

What is HER2-Positive Metastatic Breast Cancer? ²

HER2-positive breast cancer occurs when there is an excess of HER2 receptors on the surface of the tumor cell or there are multiple copies of the HER2 gene in the nucleus of a tumor cell. This type of cancer is considered aggressive because it grows and spreads quickly and has a poor prognosis.³ HER2-positive breast cancer is considered metastatic when the original tumor in the breast spreads to other parts of the body.⁵

How Perjeta May Work (Proposed Mechanism of Action)

Perjeta and trastuzumab are believed to complement each other as both bind to the HER2 receptor, but to different regions.^{1, 2, 6, 7} The combination of Perjeta and trastuzumab is thought to provide a more comprehensive blockade of HER signaling pathways.^{1, 2}

The CLEOPATRA Study

The FDA approval of Perjeta is based on results from CLEOPATRA, a Phase III, randomized, double-blind study evaluating the combination of Perjeta, trastuzumab and docetaxel chemotherapy compared to trastuzumab and docetaxel chemotherapy plus placebo in 808 people with previously untreated HER2-positive metastatic breast cancer. The study reported a 6.1-month improvement in median PFS and a 38 percent reduction in the risk of the disease worsening or death for the Perjeta, trastuzumab and docetaxel chemotherapy arm.

Perjeta Development Program

• Genentech continues to investigate Perjeta in clinical studies.
• Visit Clinicaltrials.gov for a list of ongoing Perjeta clinical studies.
• Visit Genentech Access Solutions for coverage and reimbursement support, patient assistance and information resources.

Important Safety Information and Serious Side Effects

What should patients know about side effects with 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

What is the most serious side effect?

Most Serious Side Effect: 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 6 months after a patient's last dose of Perjeta. Patients who are breastfeeding should talk with their doctor about either stopping breastfeeding or stopping Perjeta
• If a patient thinks they may be pregnant they should contact their healthcare provider immediately
• If a patient is exposed to Perjeta during pregnancy, they are encouraged to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720

What are 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 patientÕs doctor may run tests to monitor the patient's heart function before and during treatment with Perjeta
• 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 fatigue, loss of 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

How will doctors and patients know if Perjeta is the right treatment option?

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.

What are the most common side effects?

The most common side effects of Perjeta when given with Herceptin and docetaxel (chemotherapy) 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)

Report side effects to the FDA at (800) FDA-1088 or 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 www.perjeta.com.

• References

  ¹ Perjeta Prescribing Information. Genentech, Inc. June 2012.

  ² Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109-119.

  ³ Press MF, Bernstein L, Thomas PA, et al. HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. J Clin Oncol. 1997;15:2894-2904.

  ⁴ Pegram M, Slamon D. Biological rationale for HER2/neu (c-erbB2) as a target for monoclonal antibody therapy. Semin Oncol. 2000;27(suppl 9):13-19.

  ⁵ National Cancer Institute. Metastatic Cancer: Questions and Answers. http://www.cancer.gov/cancertopics/factsheet/Sites-Types/metastatic. Accessed March 5, 2012.

  ⁶ Agus DB, Akita RW, Fox WD, et al. Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell. 2002;2:127-37.

  ⁷ Franklin MC, Carey KD, Vajdos FF, et al. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004;5:317-328.

  ⁸ Scheuer W, Friess T, Burtscher H, et al. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res. 2009;69:9330-9336.

  ⁹ Lee-Hoeflich ST, Crocker L, Yao E, et al. A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res. 2008;68:5878-5887.