Pegfilgrastim benefits moderate-risk patients, too

May 2, 2005

A study of 928 breast cancer patients showed that those receiving first and subsequent cycle administration of pegfilgrastim (Neulasta, Amgen) had a whopping 94% decline in the incidence of febrile neutropenia, a 93% decline in hospitalizations, and an 80% drop in intravenous anti-infective use. The patients had been considered at moderate risk for neutropenic complications.

A study of 928 breast cancer patients showed that those receiving first and subsequent cycle administration of pegfilgrastim (Neulasta, Amgen) had a whopping 94% decline in the incidence of febrile neutropenia, a 93% decline in hospitalizations, and an 80% drop in intravenous anti-infective use. The patients had been considered at moderate risk for neutropenic complications.

Earlier trials focusing on high-risk patients found that when the drug was given prophylactically, it was associated with both reduced hospitalizations and use of IV anti-infectives.

In the current trial-the first and largest of its kind ever performed-pegfilgrastim administered 24 hours after chemotherapy in moderate-risk patients reduced the rate of febrile neutropenia from 17% to 1%, reported lead investigator Charles Vogel, M.D., Cancer Research Network, Plantation, Fla. "The high frequency of first-cycle febrile neutropenia seen here shows the need to initiate Neulasta from the start to reduce the patient's risk of infection. Febrile neutropenia is the most common presentation of infection in patients receiving chemotherapy," he emphasized. The study was published in the Feb. 20 issue of the Journal of Clinical Oncology.

Vogel pointed out that the patients (Stage 1-4, ECOG [Eastern Cooperative Oncology Group] performance 0-2) received 100 mg/m2 docetaxel every three weeks for up to four cycles; they were also randomized to receive either 6 mg pegfilgrastim (n=463) or placebo (n=465) once per cycle on the day after being administered.

Docetaxel (Taxotere, Sanofi-Aventis), like other commonly used chemotherapy drugs, is associated with an average febrile neutropenia incidence of about 10%-20% without growth factor support, said Vogel. Previous studies of growth factor impact focused on treatment associated with a high-i.e., higher than 40%-incidence of febrile neutropenia. "This landmark study shows for the first time that patients at lower risk of developing neutropenia can also benefit from pegfilgrastim use in the first cycle," he said.

Thus, current treatment guidelines should be revised since they are based on old studies (associated with a high risk of febrile neutropenia), Vogel suggested in an interview. "The threshold is too high, we're spending too much money.... We can reduce the cost of health care by using a growth factor that's effective in the lower ranges of risk."

Even more important, by judiciously using pegfilgrastim in the outpatient setting, Vogel said, "we can decrease the trauma to the breast cancer patient of hospitalization with IV treatments and all the rest...."

Asked to comment on the study, James Stevenson, Pharm.D., director of pharmacy services, University of Michigan Medical Center, said he believes its results "likely will change the standard practice guidelines so that patients in lower-intensity regimens also can benefit." He hopes a future study will look into the cost-saving aspects of pegfilgrastim use.

Similarly, John Timoney, Pharm.D., clinical specialist, Memorial Sloan-Kettering Cancer Center, agreed that the large pegfilgrastim study probably will impact current treatment guidelines-"which haven't been revised in five years." He also suggested that an analysis of healthcare costs associated with the study ... would assist in driving guideline change. "The study [understandably] didn't examine the pharmacoeconomics of the matter," he emphasized.

The Food & Drug Administration approved pegfilgrastim in 2002 for reducing the incidence of infection, as manifested by neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive chemotherapy.

Bone pain was a frequently seen adverse effect in both arms of the current study (31% with pegfilgrastim versus 27% with placebo).