On November 8, 2007, the Aranesp ( Darbepoetin alpha ) and Epogen / Procrit ( Epoetin alpha ) labeling were revised to describe the results of 6 studies showing increased mortality and more rapid tumor progression in patients with cancer receiving ESAs ( erythropoiesis-stimulating agents ).

Amgen and Ortho Biotech informed Health Care Professional on two additional trials that have been included in the product labels.
Based on the results of these studies, the Boxed Warnings section of the Epogen / Procrit and Aranesp prescribing information has been revised as follows:

Cancer

ESAs shortened overall survival and/or time to tumor progression in clinical studies in patients with advanced breast, non-small cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of less than or equal to12 g/dL.

Additional modification made to the product labels are summarized as follows:

Warnings: increased mortality and/or tumor progression section

The label has been updated based on an interim analysis for the PREPARE study. The study is ongoing and data collection and follow-up continue.
The PREPARE study was a randomized controlled study in which Aranesp was administered to prevent anemia conducted in 733 women receiving neo-adjuvant breast cancer treatment.
An interim analysis was performed after a median follow-up of approximately 3 years at which time the survival rate was lower ( 86% vs. 90%, HR 1.42 ) and relapse-free survival rate was lower ( 72% vs. 78%, HR 1.33 ) in the Aranesp-treated arm compared to the control arm.

The label has been updated based on additional follow-up of the protocol GOG 191 which was terminated prematurely in late 2003 following an unplanned review of safety data undertaken by the Gynecologic Oncology Group ( GOG ) at the request of Johnson & Johnson Pharmaceutical Research & Development.
The protocol GOG 191 was a randomized controlled study that enrolled 114 of a planned 460 cervical cancer patients receiving chemotherapy and radiotherapy.
Patients were randomized to receive Epoetin alfa to maintain hemoglobin between 12 and 14 g/dL or to transfusion support as needed.
The study was terminated prematurely due to an increase in thromboembolic events in Epoetin alfa-treated patients compared to control ( 19% vs. 9% ).
Both local recurrence ( 21% vs. 20% ) and distant recurrence ( 12% vs. 7% ) were more frequent in Epoetin alfa-treated patients compared to control. Progression-free survival at 3 years was lower in the Epoetin alfa-treated group compared to control ( 59% vs. 62%, HR 1.06 ). Overall survival at 3 years was lower in the Epoetin alfa-treated group compared to control ( 61% vs. 71%, HR 1.28 ).

Source: FDA, 2008

XagenaMedicine2008



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