Timing of Pegfilgrastim Administration and Pegfilgrastim-Induced Bone Pain : A Prospective, Randomized, Phase 3 Trial.

Abstract

Pegfilgrastim-induced bone pain (PIBP) is common and lacks effective treatment. To determine whether there is an association between the timing of pegfilgrastim administration and PIBP. Three-arm randomized controlled trial. (ClinicalTrials.gov: NCT05841186). A tertiary A-level hospital. Patients with I to III stage breast cancer who were naive to chemotherapy. Patients were randomly allocated in a 1:1:1 ratio to the 24-hour, 48-hour, or 72-hour group based on the timing of pegfilgrastim administration postchemotherapy. The primary end point was the area under the curve (AUC) of the daily worst bone pain score (assessed using the "worst pain" question from the Brief Pain Inventory, a 0 to 10 numerical rating scale [NRS]) for 5 consecutive days in the first chemotherapy cycle. Secondary end points included the incidence of severe bone pain (>5 on the NRS), neutropenia, and febrile neutropenia (FN). The intention-to-treat analyses included 159 patients, with 53 in each group. For the first cycle, in the 72-hour group, the mean AUC exhibited a statistically significant reduction from 12.74 in the 24-hour group and 14.20 in the 48-hour group to 6.05 (all <i>P <</i> 0.001). Furthermore, the incidence of severe bone pain also declined significantly from 58.5% in the 24-hour group and 66.0% in the 48-hour group to 22.6% in the 72-hour group (all <i>P <</i> 0.001). There was no substantial difference in the incidence of neutropenia among groups, and no patients developed FN. Open label, single center, and relatively small sample size. Administration of pegfilgrastim 72 hours postchemotherapy reduced PIBP compared with 24- and 48-hour administration and did not seem to be associated with higher rates of neutropenia or FN. National Natural Science Foundation of China.