Lyman, G.H., Allcott, K., Garcia, J., Stryker, S., Li, Y., Reiner, M.T., & Weycker, D. (2017). The effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: A systematic review. Supportive Care in Cancer, 25, 2619–2629.

STUDY PURPOSE: To evaluate the relative merits of same-day versus next-day dosing of long-acting G-CSFs. Study aims are to conduct a broad search of the literature, to examine the volume of data on same day versus next-day long acting G-CSFs, and to explore the relationship between timing of administration and efficacy, effectiveness, and safety

TYPE OF STUDY: Systematic review

DATABASES USED: Ovid MEDLINE^®, Embase^®, Congress abstracts

YEARS INCLUDED: (Overall for all databases) no limit up to May 8, 2016 (Ovid MEDLINE and Embase); January 1, 2011 to April 6, 2016 (Congress abstracts)

INCLUSION CRITERIA: Followed the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Publications reporting results from studies in humans in the English language, intervention included long-acting G-CSFs (pegfilgrastim, balugrastim, lipegfilgrastim, and empegfilgrastim) for the prophylaxis of chemotherapy-induced neutropenia were included. Included comparisons included long-acting G-CSF administration on the same day as chemotherapy and administration of long-acting G-CSF on the next day within the same study. Outcomes included neutropenia, leukopenia, FN, ANC, neutropenia-related infection, hospitalization, anti-infective use, or G-CSF--related safety outcome. Acceptable study designs included RCTs, prospective and retrospective non-randomized trials, longitudinal studies, registry studies, and open-label studies 

EXCLUSION CRITERIA: Studies were excluded if they did not meet inclusion criteria (most notably had no relevant outcomes, no relevant comparison between same-day and next-day long-acting G-CSF administration, wrong indication, or were not in humans), were duplicate studies, or were not deemed to be an acceptable design

TOTAL REFERENCES RETRIEVED: 1,736 publications, of which 11 were found to meet all inclusion criteria and were included in the review 

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Participants, interventions, comparisons, outcomes, and study design (PICOS) criteria were prospectively defined. Identified abstracts through the broad search were analyzed by two reviewers using PICOS criteria to determine eligibility. Full-text publications from the initial eligibility review were examined by two independent reviewers to confirm eligibility. Conflicts were resolved by a third senior reviewer. Data from eligible publications were extracted into a purpose-created data table; however, no formal statistical analysis was planned nor completed.

• FINAL NUMBER STUDIES INCLUDED: 11 studies, including 4 randomized or single-arm prospective studies, 7 retrospective studies
• TOTAL PATIENTS INCLUDED IN REVIEW: 46,979
• SAMPLE RANGE ACROSS STUDIES: Single-arm studies ranged from 19 to 192, retrospective studies ranged from 24 to 45,592
• KEY SAMPLE CHARACTERISTICS: Tumor types included non-small cell lung cancer, breast cancer, head and neck cancer, urothelial carcinoma, gynecologic malignancies, and other solid tumors. Nine of 11 studies evaluated pegfilgrastim on the same day or after chemotherapy. One study evaluated daily filgrastim or a single dose of pegfilgrastim administered on the same day or day 2-plus. One study evaluated filgrastim or pegfilgrastim administered on day 3 versus day 7 during a five-day chemotherapy course.

PHASE OF CARE: Active anti-tumor treatment

Safety: Safety results showed only small differences in the rates of all-grade adverse events and serious adverse events between the same-day and next-day pegfilgrastim groups

Neutropenia: Of the 11 publications included in the review, six reported higher rates and longer duration of neutropenia and/or FN for same-day LA G-CSF administration compared with next day administration (included data from two randomized studies and four retrospective). In these studies, same-day LA G-CSF administration was associated with increased grade 4 neutropenia compared with next-day administration in up to four treatment cycles. Retrospective safety studies and a large cohort study using claims data from more than 45,000 patients support the findings from the randomized trials that demonstrated next-day LA G-CSF administration resulted in lower rates of grade 3/4 neutropenia and/or FN compared with same-day LA G-CSF. Five studies showed lower or comparable rates and duration of neutropenia and/or FN for same-day compared to next-day LA G-CSF administration. These studies generally included small patient populations, retrospective designs, or did not have an adequate control arm to allow for accurate comparison. Nearly all studies reporting safety outcomes showed only small differences in the rates of all-grade adverse events and serious adverse events for same-day LA G-CSF versus next-day LA G-CSF.

Administration of pegfilgrastim at least 24 hours after chemotherapy (next day LA G-CSF) resulted in improved outcomes for patients with various tumor types receiving chemotherapy, including reduced incidence of grade 3/4 neutropenia and/or FN. Additionally, safety results for same-day LA G-CSF versus next-day LA G-CSF showed only small differences in the rates of all-grade adverse events and serious adverse events.

• Limited number of studies included
• Low sample sizes
• Study funded by Amgen Inc., maker of pegfilgrastim; authors are stockholders in Amgen

Findings show that administration of pegfilgrastim 24 to 72 hours after the completion of myelosuppressive chemotherapy (next-day LA G-CSF) is more effective than same-day LA G-CSF in preventing neutropenia and/or febrile neutropenia and is associated with fewer incidences of grade 3/4 neutropenia