Pooled Analyses

Because the efficacy endpoints of the two pivotal trials were similar, Shogan et al. (41) pooled these data to evaluate the efficacy of pegfilgrastim in patients 65 yr or older

Fig. 5. Days of ANC < 500 by weight quartile, cycle 1. Darker bars, pegfilgrastim 6 mg; lighter bars, filgrastim.
Fig. 6. Pegfilgrastim and filgrastim provide comparable neutrophil recovery: median absolute neutrophil count. (Adapted from ref. 36.)

using the same endpoints: DSN, rates of FN, antibiotic use, and hospitalization. In the combined trials, 59 patients were aged 65 yr or older, representing 13% of the total population of 456 patients. The distribution of the elderly patients by cohort was 14% (32/225) receiving filgrastim and 12% (27/227) receiving pegfilgrastim.

No difference in the DSN, rates of FN, antibiotic use, or hospitalization by age was seen when the younger and older patients were compared. The pooled data showed a significant decrease in the rates of FN for the pegfilgrastim group regardless of age (Fig. 6).

Shogan et al. (41) used these data to evaluate other subgroups at risk for prolonged neutropenia and its complications, namely, patients with prior chemotherapy, prior radiation therapy, a poorer performance status, and advanced (stage IV) vs early disease. In every subgroup, pegfilgrastim was more effective than filgrastim in reducing the incidence of FN (Fig. 7).

Analysis of bone pain using pooled data was attempted by Kubista et al. (42). Bone pain was different between the two studies. The incidence of bone pain was significantly

Fig. 7. Incidence of febrile neutrophenia. Open bars, pegfilgrastim; closed bars, filgrastim.

higher in the fixed-dose study compared with the weight-based study (p = 0.044), so data could not be pooled. Analyses were performed within each study. In both studies, these analyses showed that bone pain was more severe in the first course compared with later courses (p < 0.001), with both filgrastim and pegfilgrastim. Most patients, 60-70%, did not experience bone pain and a few, 5-10%, experienced it in all four courses.

The onset of bone pain tended to be earlier in patients treated with pegfilgrastim compared with filgrastim, but duration or severity was not increased compared with fil-grastim. The incidence of bone pain was evaluated by body weight in the fixed-dose study. The numbers of patients in the quartiles were so small that only the extremes were evaluated. Of the 79 patients who received pegfilgrastim, 12 (15%) weighed <60 kg, 60 (76%) weighed between 60 and 100 kg, and 7 (9%) weighed >100 kg. The incidences of bone pain in these groups were 33, 38, and 29%, respectively. The numbers are too small for conclusions, but no obvious trend for more pain in the lighter patients was seen compared with heavier patients.

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