Reductions in Hospitalization May Justify Expanded Use of Prophylactic Pegfilgrastim

SAN ANTONIO—Prophylactic pegfilgrastim (Neulasta) for patients undergoing myelosuppressive chemotherapy should be used at lower levels of febrile neutropenia risk than are currently recommended by guidelines, according to Charles L. Vogel, MD, medical director, Cancer Research Network, Inc., Plantation, Florida. Dr. Vogel based this conclusion on clinical trial findings presented at the 27th Annual San Antonio Breast Cancer Symposium (abstract 5044).

Pivotal filgrastim (Neupogen) and pegfilgrastim studies were conducted with highly myelosuppressive regimens associated with febrile neutropenia rates of 60% and 40%, respectively, and demonstrated substantial reductions. "While ASCO guidelines recommend reserving prophylactic growth factors for regimens producing febrile neutropenia rates of about 40%, many oncologists, myself included, feel that having 40% of patients hospitalized with infections is too high," Dr. Vogel said in an interview. Data suggesting clinical benefit, and, by inference, avoidance of the cost of hospitalization and intravenous antibiotics, could help justify expanded pegfilgrastim use.

In this randomized, double-blind study, supported by Amgen, breast cancer patients received docetaxel (Taxotere) 100 mg/m² every 3 weeks, a regimen with a predicted febrile neutropenia rate of about 20%. The hypothesis was that first and subsequent cycle pegfilgrastim use would significantly reduce febrile neutropenia. The investigators also planned to look at the timing of neutropenic events.

Patients were randomized to receive pegfilgrastim 6 mg (n = 463) or placebo (n = 465) on day 2 of the first cycle and then through up to four cycles of docetaxel with or without open-label pegfilgrastim. Febrile neutropenia was defined as temperature of 38.2° C or higher and absolute neutrophil count (ANC) of less than 0.5 × 10⁹/L (measured within 1 day after documented fever). Mean age of the patients was 52 years; 62% of patients had metastatic disease.

Study Results

Reductions in febrile neutropenia and related hospitalizations and intravenous anti-infective use were significant. The febrile neutropenia rate was 17% in the placebo group vs 1% in the pegfilgrastim group (P < .0001). Hospitalizations due to febrile neutropenia were required in 14% of the placebo group vs 1% of the pegfilgrastim group (P < .0001). In addition, intravenous anti-infective use due to febrile neutropenia was 10% with placebo vs 2% with pegfilgrastim.

Most cases of febrile neutropenia (65%) occurred in the first cycle, as did 65% of related hospitalizations and 60% of related intravenous anti-infective use. Grade 3-4 neutropenia was markedly reduced for patients receiving pegfilgrastim across all cycles. "You can almost entirely abrogate the febrile neutropenia problem associated with docetaxel at 100 mg/m²," Dr. Vogel commented.

Well Tolerated

Pegfilgrastim was well tolerated, and adverse events were similar in both groups. While bone pain was somewhat more common in the pegfilgrastim group (31% vs 27%), Dr. Vogel noted that it was difficult to "tease out" pegfilgrastim-induced bone pain from bone-metastasis-induced pain. From these data, the investigators estimated that there was approximately a 5% incidence of pegfilgrastim-induced bone pain. [The complete study results have beeen published in the Journal of Clinical Oncology (23:1178-1184, 2005).]

"I think these data are pretty convincing and can be generalized to any comparable regimen. Many breast cancer and other cancer regimens are in this 20% range," Dr. Vogel said. "I would like to see the guidelines changed to 20%. That would be far more reasonable than 40%." He said that a prospective cost-effectiveness study needs to be conducted.