FDA Approves Pegfilgrastim to Protect Against Chemotherapy-Related Neutropenia

March 1, 2002

The US Food and Drug Administration has approved Amgen’s pegfilgrastim (Neulasta) for use in decreasing the incidence of infection, as manifested by febrile neutropenia. The agent, administered in a single fixed dose per chemotherapy cycle, is indicated for patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy associated with a significant incidence of febrile neutropenia.

The US Food and Drug Administration hasapproved Amgen’s pegfilgrastim (Neulasta) for use in decreasing the incidenceof infection, as manifested by febrile neutropenia. The agent, administered in asingle fixed dose per chemotherapy cycle, is indicated for patients withnonmyeloid malignancies who are receiving myelosuppressive chemotherapyassociated with a significant incidence of febrile neutropenia.

Nearly 50% of cancer chemotherapy patients develop severeneutropenia, and, on average, less than 10% receive proactive protection fromneutropenia. Studies have shown that 30% to 40% of patients who receive certaintypes of chemotherapy and are not given a white blood cell booster willexperience neutropenia with fever.

Less Frequent Dosing

Until now, granulocyte colony-stimulating factor (G-CSF,filgrastim, [Neupogen]) was the only agent shown to decrease the risk ofinfection and hospitalization as a result of chemotherapy-induced neutropenia.However, the burden of frequent daily dosing (for as many as 14 consecutivedays) led many health-care professionals to delay intervention with filgrastimuntil after a neutropenic infection developed.

"The less frequent dosing of Neulasta means thatpatients will require fewer painful injections, fewer office visits for thoseinjections, and fewer disruptions to their lives at a time when they areoverwhelmed with a serious disease," said Frankie Ann Holmes, md, a leadclinical trial investigator and associate director of research at US Oncology inHouston. "This approval means that hundreds of thousands of chemotherapypatients at risk for infection may now receive Neulasta as protection at theonset of each treatment cycle before complications arise."

Proven in Clinical Trials

Data from two pivotal phase III studies in breast cancerpatients (310 receiving a 100-µg/kg dose, 157 receiving a fixed 6-mg dose)demonstrated that a single dose of pegfilgrastim provided protection frominfection comparable to a mean of 11 daily injections of standard G-CSF (5µg/kg/d). The randomized, double-blind trials were conducted in breast cancerpatients undergoing as many as four cycles of chemotherapy with doxorubicin anddocetaxel (Taxotere).

Days of severe neutropenia were comparable between treatmentgroups in all cycles. The mean duration of severe neutropenia in cycle 1appeared to be equivalent for patients in the pegfilgrastim and filgrastimgroups: an average of 1.8 vs 1.6 days, respectively, in the fixed-dose trial,and 1.7 vs 1.6 days in the by-weight dosing trial. The average weight ofpatients was 160 lb (72.4 kg), with more than 76% weighing 154 lb (70 kg)or more. Pegfilgrastim was comparable to filgrastim with respect to rates offebrile neutropenia across all chemotherapy cycles in both studies.

Data from phase II studies in patients with variousmalignancies receiving a variety of chemotherapy regimens further supported thesafety and efficacy of pegfilgrastim. These studies in patients with breastcancer, thoracic tumors (including lung cancer), non-Hodgkin’s lymphoma, andHodgkin’s disease demonstrated that the efficacy of a single injection ofpegfilgrastim (100 µg/kg) was similar to that of daily injections offilgrastim (5 µg/kg/d).

Safety Tested

Pegfilgrastim was found to be safe and well-tolerated. In clinical trials,the most common adverse event following combination chemotherapy in 465 patientswith lymphoma and solid tumors was bone pain, which was reported in 26% ofpatients. In most cases, the bone pain was controlled with nonnarcoticanalgesics. The most serious adverse event was low oxygen in the blood, reportedin one patient. In addition, although not reported in patients receivingpegfilgrastim, rare events of respiratory distress syndrome, splenic rupture,and sickle cell crisis occurred in patients receiving the parent compound,filgrastim.