Systematic Review Finds No Difference in Efficacy of Short-Acting and Long-Acting G-CSF Agents

Given that chemotherapy-induced neutropenia is one of the most frequent adverse events (AEs) associated with cytotoxic chemotherapy and often leads to febrile neutropenia (FN), effective prophylaxis with granulocyte colony-stimulating factor therapies (G-CSFs) is key. A recent systematic review of the literature reported on randomized controlled trials (RCTs) and nonrandomized studies on the use of G-CSFs to reduce the incidence of FN, and found that short- and long-acting therapies, when dosed according to guidelines, have little difference in their efficacy.

Publications eligible for inclusion in the review involved adults with nonmyeloid malignancies receiving chemotherapy. The literature search resulted in 45 eligible references. Seventeen publications reported on RCTs and 28 reported on other studies; 22 studies compared the short-acting filgrastim with the long-acting pegfilgrastim, 1 study used sargramostim as concomitant therapy, and 4 studies compared filgrastim or the short-acting lenograstim with pegfilgrastim, while 2 studies compared biosimilar filgrastim with filgrastim and pegfilgrastim.

None of the RCTs found a statistically significant difference in the incidence of FN between short- and long-acting G-CSFs. Among non-RCTs, 6 publications noted no significant difference between short- and long-acting G-CSFs, while 5 reported that pegfilgrastim was superior to filgrastim. One non-RTC reported a numerical trend toward the superiority of pegfilgrastim, but did not provide a statistical analysis. One non-RTC reported that filgrastim was more effective than pegfilgrastim.

Use of a fixed-effect model on RCTs demonstrated that although the risk of FN with long-acting G-CSFs was generally lower than with short-acting agents, the risk difference was not statistically significant. A sensitivity analysis confirmed this finding, and an analysis of non-RTCs found that the overall effect of long-acting G-CSF on FN was almost the same as that of short-acting G-CSF.

All RTCs showed similar levels of dose reduction of chemotherapy or delays in anticancer treatment for short- and long-acting agents. Three RCTs showed no significant difference in treatments in terms of hospitalization outcomes among treatments, while 2 reported a trend toward fewer hospitalizations with pegfilgrastim.

“Overall, the weight of evidence indicates little difference in efficacy between the short- and long-acting drugs if the short-acting G-CSF is dosed according to recommended guidelines,” wrote the authors.

Reference

Cornes P, Gascon P, Chan S, et al. Systematic review and meta-analysis of short- versus long-acting granulocyte colony-stimulating factors for reduction of chemotherapy-induced febrile neutropenia. Adv Ther. 2018;35(11): 1816-1829. doi: 10.1007/s12325-018-0798-6.