References

1. 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.

2. Herceptin [package insert] South San Francisco, Calif.: Genentech, Inc. October 2010.

3. Sliwkowski MX, Lofgren JA, Lewis GD, et al. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Seminars in Oncology [1999, 26(4 Suppl 12):60-70].

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

5. 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.

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.

10. KadcylaTM (ado-trastuzumab emtansine) Prescribing Information. Genentech, Inc. February, 2013.

11. Verma S, Miles D, Gianni L, et al. Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. N Engl J Med. 2012; 367(19):1783-91.

Important Safety Information and Serious Side Effects

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

Before taking the first dose of 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 MUGA scan. Some early breast cancer patients may also need to have a test done after they have finished taking 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 Herceptin.

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

Herceptin can cause harm to the fetus (unborn baby), 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 Herceptin treatment and for at least 6 months after treatment with Herceptin. Nursing mothers treated with Herceptin should discontinue nursing or discontinue 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 or stomach cancer is HER2 positive before using Herceptin, as benefit has only been shown in patients that are HER2 positive.

The most common side effects associated with 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.

The most common side effects associated with Herceptin in patients with stomach cancer are low white blood cell counts, diarrhea, fatigue, low red blood cell counts, inflammation of the lining of the mouth, weight loss, upper respiratory tract infections, fever, low platelet counts, swelling of mucus membranes, swelling of the nose and throat, and a change in taste.

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

Patients should read the Herceptin Full Prescribing Information including Boxed WARNINGS, at www.herceptin.com.

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.

Important Safety Information

Kadcyla is not the same medicine as Herceptin.

There are possible serious side effects of Kadcyla. Patients must contact their doctor right away if they experience any of these symptoms. The patient’s doctor may do tests before starting Kadcyla and before each dose to monitor for these side effects. Kadcyla treatment may be stopped or the dose may be lowered if the patient experiences any of these side effects.

Liver Problems

• Kadcyla may cause severe liver problems that can be life-threatening. Symptoms of liver problems may include vomiting, nausea, stomach pain, dark urine or itching.

Heart Problems

• Kadcyla may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure). Symptoms may include swelling of the ankles or legs, shortness of breath, cough, or rapid weight gain of greater than five pounds in less than 24 hours.

Pregnancy

• Receiving Kadcyla during pregnancy can result in the death of an unborn baby and birth defects. Birth control should be used while patients receive Kadcyla and for six months after their last dose of Kadcyla.
• If patients are exposed to Kadcyla during pregnancy, they must contact their healthcare provider right away; they are also encouraged to enroll in the MotHER Pregnancy Registry by contacting (800) 690-6720.
• If patients are mothers who are breastfeeding, they should talk with their doctor about either stopping breastfeeding or stopping treatment with Kadcyla.

Additional Possible Serious Side Effects of Kadcyla

Lung Problems

• Kadcyla may cause lung problems, including inflammation of the lung tissue, which can be life-threatening. Signs of lung problems may include trouble breathing, cough, tiredness and fluid in the lungs.

Infusion-Related Reactions

• Symptoms of an infusion-related reaction may include one or more of the following: the skin getting hot or red (flushing), chills, fever, trouble breathing, low blood pressure, wheezing, tightening of the muscles in the chest around the airways or a fast heartbeat. The patient’s doctor will monitor the patient for infusion-related reactions.

Low Platelet Count

• Low platelet count may happen during treatment with Kadcyla. Platelets are cells in the blood that help the blood clot.

Nerve Damage

• Symptoms may include numbness and tingling, burning or sharp pain, sensitivity to touch, lack of coordination, or muscle weakness or loss of muscle function. 

Skin Reactions Around the Infusion Site 

• Kadcyla may leak from the vein or needle and cause reactions such as redness, tenderness, skin irritation, or pain or swelling at the infusion site. If this happens, it is more likely to happen within 24 hours of the infusion.

HER2 Testing and Kadcyla 

Patients must have a HER2 test to determine if their cancer is HER2-positive before taking Kadcyla, as benefit has only been shown in patients whose tumors are HER2-positive.

Most Common Side Effects of Kadcyla

In clinical studies, the most common side effects seen in people taking Kadcyla were:

• Tiredness
• Nausea
• Pain that affects the bones, muscles, ligaments and tendons 
• Low platelet count
• Headache
• Liver problems 
• Constipation

The most common severe side effects of Kadcyla were:

• Low platelet count
• Liver problems 
• Low levels of red blood cells
• Nerve problems
• Low levels of potassium in the blood
• Tiredness

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.

For full Prescribing Information and Boxed WARNINGS on Kadcyla, please visit http://www.kadcyla.com.