In a phase II study reported in the Journal of Clinical Oncology, Vaz-Luis et al found that the use of a prespecified algorithm enabled the avoidance of routine peg-filgrastim prophylaxis during the paclitaxel portion of neoadjuvant or adjuvant treatment with dose-dense doxorubicin/cyclophosphamide/paclitaxel in patients with breast cancer.
“Omission of routine peg-filgrastim during dose-dense paclitaxel according to a prespecified algorithm seems to be safe and feasible and was associated with a 95.7% reduction in the use of peg-filgrastim relative to the current standard of care.”— Vaz-Luis et al
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Study Details
The study enrolled patients at five U.S. sites between May 2016 and November 2018. A total of 125 patients aged ≤ 65 years who completed four cycles of dose-dense doxorubicin/cyclophosphamide for stage I to III breast cancer were to receive paclitaxel at 175 mg/m2 every 2 weeks for four cycles. Peg-filgrastim was administered after paclitaxel only if patients experienced febrile neutropenia in a prior cycle or at investigator discretion if patients had infections or treatment delays ≥ 1 week. Any patient who received peg-filgrastim received it in all subsequent cycles.
The primary endpoint was the rate of paclitaxel completion within 7 weeks from day 1 of cycle 1 to day 1 of cycle 4. The regimen was to be considered feasible if ≥ 100 out of the 125 enrolled patients completed four cycles of paclitaxel without a dose delay.
Key Findings
Overall, 112 patients (90%) completed dose-dense paclitaxel within 7 weeks, thus meeting the feasibility criterion. Omission of peg-filgrastim was not causally related to failure to complete paclitaxel treatment in any patient. Febrile neutropenia occurred in one patient but did not result in delay in completion of paclitaxel.
In total, eight patients (6.4%) received peg-filgrastim, with peg-filgrastim being administered in 4.3% of paclitaxel cycles.
Among the 13 patients who did not complete paclitaxel treatment within 7 weeks, 3 patients completed four cycles in > 7 weeks. Delay in two of these patients was due to nonhematologic causes. The remaining patient had a nonneutropenic active infection during cycle 2 and grade 3 neutropenia during cycle 3. Among 10 patients who did not complete four cycles of therapy, nonhematologic adverse events occurred in 9, and 1 withdrew from the study.
Among 23 patients who completed four cycles within 43 to 49 days (> 6 and < 7 weeks), dose delays were due to scheduling/holidays/patient preference in 12, neutropenia without fever in 9, febrile neutropenia in 1, and nonhematologic toxicity in 1.
Overall, 11 patients (8.8%) had a dose delay of any duration that was due to neutropenia, with delay lasting longer than 7 days in 1 (0.8%).
The authors concluded, “Omission of routine peg-filgrastim during dose-dense paclitaxel according to a prespecified algorithm seems to be safe and feasible and was associated with a 95.7% reduction in the use of peg-filgrastim relative to the current standard of care.”
Nancy U. Lin, MD, of the Department of Medical Oncology, Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Friends of Dana-Farber Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
