By: Liam Davenport
Women with early-stage breast cancer had a significantly lower rate of febrile neutropenia when given granulocyte-colony stimulating factors (G-CSF) alongside their chemotherapy rather than the antibiotic ciprofloxacin, indicate new data from a randomized trial.
The research was presented at the 2020 annual meeting of the American Society of Clinical Oncology, held virtually because of the coronavirus pandemic.
Lead author Mark J. Clemons, MD, Cancer Research Group, Ottawa Hospital Research Institute, Canada, said that, despite not meeting its composite primary endpoint of neutropenia-related hospitalizations, G-CSF was shown to be “superior” in terms of febrile neutropenia rates to ciprofloxacin, yielding an absolute 10% reduction.
He added that “due to the financial cost of G-CSF and the inconvenience of administration, our study shows that the choice of primary prophylaxis should be carefully discussed with the patient.”
Although Clemons noted that a formal economic analysis is ongoing, “the current analysis suggests that the number needed to treat with growth factors over ciprofloxacin to avoid an episode febrile neutropenia is about 18 patients.”
Study discussant Lynne I. Wagner, PhD, Wake Forest School of Medicine, Winston-Salem, North Carolina, commented that “the results from this trial do not provide a definitive recommendation for prophylaxis, though [they] generate data that is important to inform decision-making discussions between patients and their providers, and evaluating the trade-offs between both treatment strategies.”
She added that the economic analysis the authors have undertaken “will play a key role in defining reimbursement policies.”
“Additional research should improve our understanding of risk stratification in identifying patients at greater risk for febrile neutropenia and adverse outcomes,” she explained. It should also “incorporate patient preferences with regard to the trade-off between the extra visit required for G-CSF injection vs taking an oral medication, which offers greater convenience but limited benefit with regard to overall immune function”.
Wagner pointed out that this “equation is much more complicated when taking into account the current COVID pandemic and the risks associated with increased vulnerability to infection.
“Models for home-based care should be explored in an attempt to strike the right balance between optimizing outcomes, patient convenience, and reducing COVID exposure.”
Stewart B. Fleishman, MD, Coachella Valley Volunteers in Medicine, Indio, California, said in a highlights session: “The important thing here is it was an open-label, randomized, real-world trial that could be duplicated in your facility.”
“The take-away messages here are that it’s a preemptive attempt at prophylaxis with G-CSF, not waiting for it to happen,” he said.
That, for him, is about “doing what we do, but better.”
Fleishman added that the intervention used in the study is “easy” to perform “in most ambulatory areas.”
Further Study Details
Clemons began his presentation by noting that febrile neutropenia “is common with chemotherapy” and that the ASCO clinical practice guidelines recommend the prophylactic use of growth factors when the risk of febrile neutropenia is 20% or more, and “no other equally effective and safe regimen that does not require CSF is available.”
“However, there are important differences in costs, route for administration, and toxicity with these two agents” and, with a lack of randomized trials comparing G-CSF with antibiotics, the optimal febrile neutropenia prophylaxis for TC chemotherapy is “unknown.”
The team therefore conducted REaCT, initially as a feasibility study and then a definitive study, involving patients with early-stage breast cancer who received TC chemotherapy every 3 weeks for four or six cycles.
They were randomly assigned to G-CSF of any type (including biosimilars, dose, or duration) or ciprofloxacin 500 mg twice daily for 7 to 14 days starting 5 days after chemotherapy.
Patients were assessed only at their usual clinic visits, with the primary endpoint being either febrile neutropenia or nonfebrile neutropenia treatment-related hospitalizations.
Of 458 patients eligible for inclusion in the study, 228 in the ciprofloxacin group and 230 in the G-CSF group were available for the intention-to-treat analysis; 221 and 222 patients, respectively, were available for the per protocol analysis.
The study did not meet its primary endpoint, with the composite endpoint observed in 20.2% of ciprofloxacin patients and 13.5% of those in the G-CSF group, at a risk difference of –6.7% (P = .061).
However, G-CSF was associated with a significant reduction in the rate of febrile neutropenia, at 5.7% vs 15.8% with ciprofloxacin, or a risk difference of
–10.1% (95% CI –15.7% to –4.5%).
Clemons nevertheless pointed out that, for both interventions, the rate of febrile neutropenia rate was “below the 20% cutoff that was set in ASCO’s guideline for the use of growth factors.”
There was also a trend toward a reduction in treatment related hospitalizations, at 12.2% for the G-CSF group vs 17.5% for ciprofloxacin, and a risk reduction of 5.4% (95% CI –11.9% to 1.1%), but no associations with chemotherapy dose reductions, delays, or discontinuations.
Clemons highlighted that the majority of clinical endpoints occurred during the first treatment cycle.
Febrile neutropenia and treatment-related hospitalization were experienced by 10.4% and 11.3% of patients, respectively, during the first cycle in the ciprofloxacin group and in 4.5% and 6.8% of patients, respectively, in the G-CSF group.
Clemons also noted that the study was limited by being open-label and conducted in a single country, as well as by the low use of the G-CSF pegfilgrastim; he underlined, however, that the study was appropriately powered and followed real-world practice.
The study was funded by the Canadian Institute of Health Research – Strategy for Patient Oriented Research Grant, Cancer Care Ontario Clinical Programs and Quality Initiatives grant. Clemons reports a consulting or advisory role with Apob. Other study authors report potential conflicts of interest. The full list can be found here.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.