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Label Warnings for Epoetin Alfa Amended
Modifications to the label were based on an unplanned interim analysis of Amgen's PREPARE study in women with breast cancer receiving preoperative chemotherapy, and from GOG-191, a study of advanced cervical cancer patients conducted by the Gynecologic Oncology Group with support from Ortho Biotech. Both investigational studies were designed to evaluate the efficacy of maintaining hemoglobin levels greater than 12 grams per deciliter of blood (g/dL) and observed lower survival in patients being treated with ESAs. However, neither study showed a statistically significant effect on survival or tumor outcomes.
"These studies are consistent with results from previous studies demonstrating that ESAs should not be used to enhance the response to chemotherapy or radiotherapy, and should be administered to achieve a hemoglobin level of less than 12 g/dL," said Craig Tendler, M.D., Vice President, Medical Affairs, Oncology/ Nephrology, Ortho Biotech Products, L.P. "We look forward to thoughtful consideration of the totality of available scientific evidence at next week's FDA Oncologic Drugs Advisory Committee Meeting (ODAC), including a substantial body of data that has been submitted to the agency over the past several months."
Ortho Biotech remains confident in the safety and efficacy of PROCRIT when used at the lowest dose to avoid transfusion in anemic patients receiving concomitant chemotherapy. The company also remains committed to continuing to work with the FDA to ensure that physicians have the most up-to-date information to support the most appropriate use of the product.
About PREPARE and GOG-191
PREPARE was a study in patients receiving neo-adjuvant breast cancer treatment in which darbepoetin alfa was administered to prevent anemia at target hemoglobin levels of 12.5-13 g/dL. After a median follow up of approximately three years, relapse-free survival (72% versus 78%), and overall survival (86% versus 90%), were lower in darbepoetin alfa-treated patients.
GOG-191 evaluated the efficacy of maintaining hemoglobin levels between 12-14 g/dL in patients with advanced cervical cancer undergoing chemotherapy or radiotherapy. Progression-free survival (59% versus 62%) at three years, and overall survival (61% versus 71%), were lower in Epoetin alfa-treated patients.
The Boxed Warnings have been modified to now read:
WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION
Renal failure: Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.
- ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of greater than or equal to 12 g/dL.
- The risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to target a hemoglobin of To minimize these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions.
- Use only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
- Discontinue following the completion of a chemotherapy course.
(See WARNINGS: Increased Mortality, Serious Cardiovascular and Thromboembolic Events, WARNINGS: Increased Mortality and/or Tumor Progression, and DOSAGE AND ADMINISTRATION.)
Additional changes were made in the Warnings section of the label to reflect these two studies.
The company has worked closely with the FDA to ensure that the updated PROCRIT label provides physicians and patients with the information they need to make the most appropriate and informed treatment decisions. To that end, Ortho Biotech is committed to disseminating this modified prescribing information through a "Dear Health Care Provider" letter, its product Web site and its product specialists.
About PROCRIT (Epoetin alfa)
PROCRIT is used for the treatment of anemia in patients with most types of cancer receiving chemotherapy, with chronic renal failure who are on dialysis and those who are not on dialysis, who are being treated with zidovudine for HIV infection, and to reduce the need for transfusion in anemic patients who are scheduled for elective noncardiac, nonvascular surgery. Depending on the country in which Epoetin alfa is marketed, these indications may differ.
Source: Ortho Biotech Products