ASCO UPDATES GUIDELINES FOR CSFs USE

The American Society of Clinical Oncology (ASCO) has updated its 2006 clinical practice guideline on the use of hematopoietic colony-stimulating factors (CSFs) in patients with cancer who are undergoing chemotherapy.

CSFs can reduce the duration and severity of neutropenia as well as lower the risk for febrile neutropenia, and when indicated, they can allow patients to receive more intensive dose treatment. But in response to concerns about adverse events and cost, ASCO developed a clinical practice guideline for the use of CSFs in 1994. Although it has updated the guidelines on four other occasions, the new report will be the first major update since 2006.

This new update is the result of a formal systematic review of relevant medical literature published from October 2005 through September 2014 by an ASCO Expert Panel and was published online July 13 in the Journal of Clinical Oncology.

"These medications are still considered to be effective and have made febrile neutropenia less common than it used to be for similar treatment regimens," commented panel cochair Thomas J. Smith, MD.

"There is still some underuse and overuse that [Quality Oncology Practice Initiative] and insurers should be checking," said Dr Smith, who is also professor of oncology and director of palliative medicine, Johns Hopkins Medicine, Johns Hopkins Hospital, Baltimore, Maryland. "But that was not really the mandate."

New and important information has been added to the guidelines, he noted.

One important change, Dr Thomas told Medscape Medical News, is that there is no advantage to giving CSFs routinely to patients with lymphoma receiving an R-CHOP (rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone) regimen, Dr Thomas said. "There is also no indication to routinely give CSFs in lymphoma until the risk of febrile neutropenia is about 20%."

Another addition to the guidelines is that M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) for urothelial cancers in dose-intensive mode is now on the list of regimens that require CSFs.

The new guidelines also stipulate that lower-cost biosimilars can replace filgrastim (Neupogen, Amgen).

"The lower-cost biosimilars are especially important in hospital use," Dr Thomas said.

A biosimilar for pegfilgrastim (Neulasta, Amgen) has not yet come on the market, but 10 days of a biosimilar or filgrastim would be considered acceptable, he added, "But definitely not preferred by patients."

Also of importance is that no new risks have been identified with the use of these agents since the 2006 guidelines. "The putative risk of leukemia and myelodysplasia has not really appeared, other than that the age of the patient predisposes them to some increased risk," he said, referring to previous reports that suggested a "slight excess risk" of acute myeloid leukemia and myelodysplastic syndromes in patients treated with CSFs.

Key Recommendations

In their guidelines, ASCO identified other key recommendations that received a "strong" recommendation:

• Primary prophylaxis with a CSF starting with the first cycle and continuing through subsequent cycles of chemotherapy is recommended in patients who have an approximately 20% or higher risk for febrile neutropenia on the basis of patient-, disease-, and treatment-related factors. Consideration should be given to alternative, equally effective, and safe chemotherapy regimens not requiring CSF support when available.
• Dose-dense regimens with CSF support should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Efficacy data support the use of CSFs with dose-dense chemotherapy in the adjuvant treatment of high-risk breast cancer and with high dose intensity methotrexate, vinblastine, doxorubicin, and cisplatin (HD-M-VAC) in urothelial cancer.
• Secondary prophylaxis with a CSF is recommended for patients who experienced a neutropenic complication from a prior cycle of chemotherapy (for which primary prophylaxis was not received) in which a reduced dose or treatment delay may compromise disease-free or overall survival or treatment outcome.
• CSFs should not be routinely used for patients with neutropenia who are afebrile.
• CSFs should not be routinely used as adjunctive treatment with antibiotic therapy for patients with fever and neutropenia, but should be considered in patients with fever and neutropenia who are at high risk for infection-associated complications or who have prognostic factors predictive of poor clinical outcomes.
• CSFs should be administered after autologous stem-cell transplantation to reduce the duration of severe neutropenia.
• The use of CSFs in pediatric patients will almost always be guided by clinical protocols. As in adults, the use of CSFs is reasonable as primary prophylaxis for those with a high likelihood of febrile neutropenia, and their use for secondary prophylaxis or for therapy should be limited to high-risk patients.

J Clin Oncol. Published online July 13, 2015. Full text