Data from the EPO-ANE-3010 Study Evaluating Epoetin Alfa Presented at San Antonio Breast Cancer Symposium

Dec 12, 2014, 12:15 ET from Janssen Research & Development, LLC

RARITAN, N.J. and SAN ANTONIO, Dec. 12, 2014 /PRNewswire/ -- Janssen Research & Development, LLC (Janssen) today announced the presentation of data at the San Antonio Breast Cancer Symposium (SABCS) from the Phase 3 EPO-ANE-3010 study evaluating epoetin alfa plus best supportive care (BSC) versus BSC when used to treat anemia in patients with metastatic breast cancer receiving standard chemotherapy. This non-inferiority trial did not meet its primary objective, which was to rule out a 15 percent or greater increase in the risk of progression in the epoetin alfa plus BSC group compared with BSC. The safety results of this study are consistent with the current U.S. Food and Drug Administration (FDA) approved label for PROCRIT® (epoetin alfa), including the Boxed Warning. When used according to the approved label, PROCRIT can help patients avoid blood transfusions.

The data show a numerically increased risk of adverse tumor outcomes, although not statistically significant, that is generally consistent with observations in other studies described in the current label. Since March 2007, the U.S. label has contained a Boxed Warning stating that erythropoiesis-stimulating agents (ESAs) shorten overall survival (OS) and/or increase the risk of tumor progression. In addition, since 2010, the FDA has required a Risk Evaluation and Mitigation Strategy (REMS) for ESAs. This program ensures the decision to initiate treatment begins with a discussion between the cancer patient and healthcare provider about the risks and benefits associated with ESA therapy. The REMS requires that any healthcare provider who prescribes, or has the potential to prescribe, and any hospital that dispenses, or has the potential to dispense, an ESA for a patient with cancer must train and enroll in the ESA APPRISE Oncology Program.

ESAs such as PROCRIT stimulate the production of red blood cells (RBCs) and are an important treatment option for patients with certain types of anemia, including chemotherapy-induced anemia and anemia due to chronic kidney disease. Without ESAs, patients with certain types of anemia may require regular blood transfusions to maintain RBCs at concentrations necessary to sustain normal oxygen levels throughout the body.

"Patient safety is our highest priority. We conducted this additional research to better understand the safety and efficacy of PROCRIT when used to treat anemia in women receiving chemotherapy for metastatic breast cancer," said Craig Tendler, M.D., Vice President, Late-Stage Development and Global Medical Affairs for Oncology, Hematology and Supportive Care. "Physicians, together with their patients, will continue to need to carefully assess and discuss the risks and benefits of using epoetin alfa, as compared to red blood cell transfusions, for the treatment of chemotherapy-associated anemia in this setting of metastatic breast cancer."

EPO-ANE-3010 was conducted as part of a post-marketing requirement following the FDA Oncology Drug Advisory Committee (ODAC) meeting in 2004. In consultation with the FDA, Janssen designed this randomized, open-label, non-inferiority, multicenter Phase 3 study to evaluate the impact of epoetin alfa on progression-free survival (PFS). The primary objective was to demonstrate epoetin alfa does not increase the hazard rate of PFS by 15 percent or more as compared with BSC.  Secondary endpoints included OS, time to tumor progression (TTP), objective response rate (ORR), and incidence and severity of thrombotic vascular events (TVE). EPO-ANE-3010 is the longest and largest clinical study Janssen has conducted in oncology.

A total of 2,098 patients were enrolled into the study between March 2006 and April 2014 in 19 countries. Patients within the U.S. received PROCRIT and patients outside of the U.S. received EPREX® (epoetin alfa). An Independent Data Monitoring Committee (IDMC) has conducted 17 safety reviews of the data.

PFS as assessed by the investigator-determined progressive disease (PD) based on 1,659 events was 7.4 months in both groups (HR 1.089, 95% CI [0.988, 1.200]). PFS as assessed by the independent review committee-determined PD based on 1,321 events was 7.6 months in both groups (HR 1.028, 95% CI [0.922, 1.146]). As of the clinical cutoff for PFS, a total of 1,337 deaths were reported. Median survival was 17.2 months in the epoetin alfa plus BSC group and 17.4 months in the BSC group (HR 1.057, 95% CI [0.949-1.177]). Overall survival will not reach maturity until 1,650 deaths have occurred.  Patients in the epoetin alfa plus BSC group were twice as likely to have a TVE as those in the BSC group (2.5 percent versus 1.5 percent).  Overall, epoetin alfa reduced the risk of transfusion by 50 percent as compared to BSC (11.4 percent versus 5.8 percent).

Overall incidence of common toxicity criteria (NCI CTC) Grade ≥ 3 adverse events and incidence of serious adverse events was similar between the epoetin alfa plus BSC group and the BSC group: 58 percent in the epoetin alfa plus BSC group and 60 percent in the BSC group.

Since PROCRIT launched in 1989, Janssen has continued to work closely with the FDA and other global health authorities to understand the best use of this product and inform the healthcare professionals who prescribe it. PROCRIT has been approved for certain types of anemia for more than 25 years, and the safety and efficacy of ESAs have been evaluated in multiple studies in patients with certain types of anemia during this timeframe.

About PROCRIT® (epoetin alfa)

PROCRIT is indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and not on dialysis to decrease the need for red blood cell (RBC) transfusion. PROCRIT is indicated for the treatment of anemia due to zidovudine administered at ≤ 4200 mg/week in HIV-infected patients with endogenous serum erythropoietin levels of ≤ 500 units/mL. PROCRIT is indicated for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy. PROCRIT is indicated to reduce the need for allogeneic RBC transfusions among patients with perioperative hemoglobin > 10 to ≤ 13 g/dL who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery. PROCRIT is not indicated for patients who are willing to donate autologous blood pre-operatively. PROCRIT has not been shown to improve quality of life, fatigue, or patient well-being.

PROCRIT is not indicated for use:

  • In patients with cancer receiving hormonal agents, biologic products, or radiotherapy, unless also receiving concomitant myelosuppressive chemotherapy.
  • In patients with cancer receiving myelosuppressive chemotherapy when the anticipated outcome is cure.
  • In patients scheduled for surgery who are willing to donate autologous blood.
  • In patients undergoing cardiac or vascular surgery.
  • As a substitute for RBC transfusions in patients who require immediate correction of anemia.

INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS

PROCRIT® may be used to treat a lower than normal number of red blood cells (anemia) if it is caused by:

  • Chronic kidney disease (you may or may not be on dialysis).
  • Chemotherapy that will be used for at least two months after starting PROCRIT®.
  • A medicine called zidovudine (AZT) used to treat HIV infection.

PROCRIT® may also be used to reduce the chance you will need red blood cell transfusions if you are scheduled for certain surgeries where a lot of blood loss is expected. 

PROCRIT® should not be used for treatment of anemia:

  • If you have cancer and you will not be receiving chemotherapy that may cause anemia for at least 2 more months.
  • If you have a cancer that has a high chance of being cured.
  • In place of emergency treatment for anemia (red blood cell transfusions).

PROCRIT® has not been proven to improve quality of life, fatigue, or well-being. 

PROCRIT® should not be used to reduce the chance of red blood cell transfusions if:

  • You are scheduled for surgery on your heart or blood vessels.
  • You are able and willing to donate blood prior to surgery.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about PROCRIT® (epoetin alfa)?

Using PROCRIT® can lead to death or other serious side effects. 

For patients with cancer:

Your healthcare provider has received special training through the ESA APPRISE Oncology Program in order to prescribe PROCRIT®. Before you can begin to receive PROCRIT®, you must sign the patient-healthcare provider acknowledgment form. When you sign this form, you are stating that your healthcare provider talked with you about the risks of taking PROCRIT®.

These risks include that your tumor may grow faster and you may die sooner if you choose to take PROCRIT®

You should talk with your healthcare provider about:

  • Why PROCRIT® treatment is being prescribed for you.
  • What are the chances you will get red blood cell transfusions if you do not take PROCRIT®.
  • What are the chances you will get red blood cell transfusions even if you take PROCRIT®.
  • How taking PROCRIT® may affect the success of your cancer treatment.

After you have finished your chemotherapy course, PROCRIT® treatment should be stopped. 

For all patients who take PROCRIT®, including patients with cancer or chronic kidney disease:

  • If you decide to take PROCRIT®, your healthcare provider should prescribe the smallest dose of PROCRIT® that is needed to reduce your chance of getting red blood cell transfusions.
  • You may get serious heart problems such as heart attack, stroke, heart failure, and may die sooner if you are treated with PROCRIT® to reach a normal or near-normal hemoglobin level.
  • You may get blood clots at any time while taking PROCRIT®. If you are receiving PROCRIT® for any reason and you are going to have surgery, talk to your healthcare provider about whether or not you will need to take a blood thinner to lessen the chance of blood clots during or following surgery. Clots can form in blood vessels (veins), especially in your leg (deep venous thrombosis or DVT). Pieces of a blood clot may travel to the lungs and block the blood circulation in the lungs (pulmonary embolus).

Call your healthcare provider or get medical help right away if you have any of these symptoms of blood clots:

  • Chest pain
  • Trouble breathing or shortness of breath
  • Pain in your legs, with or without swelling
  • A cool or pale arm or leg
  • Sudden confusion, trouble speaking, or trouble understanding others' speech
  • Sudden numbness or weakness in your face, arm, or leg, especially on one side of your body
  • Sudden trouble seeing
  • Sudden trouble walking, dizziness, loss of balance or coordination
  • Loss of consciousness (fainting)
  • Hemodialysis vascular access stops working

See "What are the possible side effects of PROCRIT®?" below. 

What is PROCRIT®?

PROCRIT® is a man-made form of the protein human erythropoietin that is given to reduce or avoid the need for red blood cell transfusions. PROCRIT® stimulates your bone marrow to make more red blood cells. Having more red blood cells raises your hemoglobin level. If your hemoglobin level stays too high or if your hemoglobin goes up too quickly, this may lead to serious health problems which may result in death. These serious health problems may happen even if you take PROCRIT® and do not have an increase in your hemoglobin level. 

PROCRIT® may be used to treat a lower than normal number of red blood cells (anemia) if it is caused by:

  • Chronic kidney disease (you may or may not be on dialysis).
  • Chemotherapy that will be used for at least two months after starting PROCRIT®.
  • A medicine called zidovudine (AZT) used to treat HIV infection.

PROCRIT® may also be used to reduce the chance you will need red blood cell transfusions if you are scheduled for certain surgeries where a lot of blood loss is expected. 

PROCRIT® should not be used for treatment of anemia:

  • If you have cancer and you will not be receiving chemotherapy that may cause anemia for at least 2 more months.
  • If you have a cancer that has a high chance of being cured.
  • In place of emergency treatment for anemia (red blood cell transfusions).

PROCRIT® has not been proven to improve quality of life, fatigue, or well-being. 

PROCRIT® should not be used to reduce the chance of red blood cell transfusions if:

  • You are scheduled for surgery on your heart or blood vessels
  • You are able and willing to donate blood prior to surgery

Who should not take PROCRIT®?

Do not take PROCRIT® if you:

  • Have cancer and have not been counseled by your healthcare provider regarding the risks of PROCRIT® or if you have not signed the patient-healthcare provider acknowledgment form before you start PROCRIT® treatment.
  • Have high blood pressure that is not controlled (uncontrolled hypertension).
  • Have been told by your healthcare provider that you have or have ever had a type of anemia called Pure Red Cell Aplasia (PRCA) that starts after treatment with PROCRIT® or other erythropoietin protein medicines.
  • Have had a serious allergic reaction to PROCRIT®.

Do not give PROCRIT® from multi-dose vials to:

  • Pregnant or breastfeeding women
  • Babies

What should I tell my healthcare provider before taking PROCRIT®?

PROCRIT® may not be right for you. Tell your healthcare provider about all your health conditions, including if you:

  • Have heart disease.
  • Have high blood pressure.
  • Have had a seizure (convulsion) or stroke.
  • Have any other medical conditions.
  • Are pregnant or planning to become pregnant. It is not known if PROCRIT® may harm your unborn baby. Talk with your healthcare provider about possible pregnancy and birth control choices that are right for you.
  • Are breast-feeding or planning to breast-feed. It is not known if PROCRIT® passes into breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. 

Know the medicines you take. Keep a list of your medicines with you and show it to your healthcare provider when you get a new medicine. 

How should I take PROCRIT®?

See "What is the most important information I should know about PROCRIT®?" 

For patients with cancer:

Before you begin to receive PROCRIT®, your healthcare provider will:

  • Ask you to review this PROCRIT® Medication Guide.
  • Explain the risks of PROCRIT® and answer all your questions about PROCRIT®.
  • Have you sign the patient-healthcare provider acknowledgment form.

For all patients who take PROCRIT®:

  • Continue to follow your healthcare provider's instructions for diet and medicines, including medicines for high blood pressure, while taking PROCRIT®.
  • Have your blood pressure checked as instructed by your healthcare provider.
  • If you or your caregiver has been trained to give PROCRIT® shots (injections) at home:
    • Be sure that you read, understand, and follow the "Instructions for Use" that come with PROCRIT®.
    • Take PROCRIT® exactly as your healthcare provider tells you to. Do not change the dose of PROCRIT® unless told to do so by your healthcare provider.
    • Your healthcare provider will show you how much PROCRIT® to use, how to inject it, how often it should be injected, and how to safely throw away the used vials, syringes, and needles.
    • If you miss a dose of PROCRIT®, call your healthcare provider right away and ask what to do.
    • If you take more than the prescribed amount of PROCRIT®, call your healthcare provider right away.

What are the possible side effects of PROCRIT®?

PROCRIT® may cause serious side effects.

  • See "What is the most important information I should know about PROCRIT® (epoetin alfa)?"
  • High blood pressure. High blood pressure is a common side effect of PROCRIT® in patients with chronic kidney disease. Your blood pressure may go up or be difficult to control with blood pressure medicine while taking PROCRIT®. This can happen even if you have never had high blood pressure before. Your healthcare provider should check your blood pressure often. If your blood pressure does go up, your healthcare provider may prescribe new or more blood pressure medicine.
  • Seizures. If you have any seizures while taking PROCRIT®, get medical help right away and tell your healthcare provider.
  • Antibodies to PROCRIT®. Your body may make antibodies to PROCRIT®. These antibodies can block or lessen your body's ability to make red blood cells and cause you to have severe anemia. Call your healthcare provider if you have unusual tiredness, lack of energy, dizziness, or fainting. You may need to stop taking PROCRIT®.
  • Serious allergic reactions. Serious allergic reactions can cause a rash over your whole body, shortness of breath, wheezing, dizziness and fainting because of a drop in blood pressure, swelling around your mouth or eyes, fast pulse, or sweating. If you have a serious allergic reaction, stop using PROCRIT® and call your healthcare provider or get medical help right away.
  • Dangers of giving PROCRIT® to newborns, infants, and pregnant or breastfeeding women. Do not use PROCRIT® from multi-dose vials in newborns, infants, pregnant or breastfeeding women because the PROCRIT® in these vials contains benzyl alcohol. Benzyl alcohol has been shown to cause brain damage, other serious side effects, and death in newborn and premature babies. PROCRIT® that comes in single-dose vials does not contain benzyl alcohol. See "Who should not take PROCRIT®?"

Common side effects of PROCRIT® include:

  • Joint, muscle, or bone pain
  • Fever
  • Cough
  • Rash
  • Nausea
  • Vomiting
  • Soreness of mouth
  • Itching
  • Headache
  • Redness and pain in the skin where PROCRIT® shots were given

These are not all of the possible side effects of PROCRIT®. Your healthcare provider can give you a more complete list. Tell your healthcare provider about any side effects that bother you or that do not go away. 

Please read the accompanying Medication Guide for PROCRIT® (epoetin alfa) and discuss it with your doctor.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit: www.fda.gov/medwatch, or call 1-800-FDA-1088.

About Janssen Research & Development, LLC

At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for more information.

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