Risks and consequences of travel burden on prophylactic granulocyte colony-stimulating factor administration and incidence of febrile neutropenia in an aged Medicare population

<p><b>Objective:</b> Granulocyte colony-stimulating factors (G-CSFs) decrease the incidence of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. This study examines the impact patient travel burden has on administration of prophylactic G-CSFs and the subsequent impact on FN incidence.</p> <p><b>Methods:</b> Medicare claims data were used to identify a cohort of beneficiaries age 65+ with non-myeloid cancers at high risk for FN between January 2012 and December 2014. Driving distance and time were calculated from patient residence ZIP code to the location of G-CSF and/or chemotherapy administration. Regression models were used to estimate the odds of G-CSF prophylaxis relative to patient driving distance and time, and odds of FN incidence relative to timing of G-CSF administration (optimal [days 2–4 after chemotherapy], sub-optimal [same day], or none).</p> <p><b>Results:</b> The 52,389 study patients had a mean age of 73.5 years, and were 82% female and 89% white race; 49% had female breast cancer, 12% lung cancer, 15% ovarian cancer, and 24% non-Hodgkin’s lymphoma. Of these high FN risk patients, 69% had at least one prophylactic G-CSF administration within at least one chemotherapy cycle. The percentage of patients receiving prophylactic G-CSFs in the first cycle was 56%. Median travel time was slightly longer for patients who did not receive G-CSFs and patients receiving short-acting vs long-acting G-CSFs. The odds of receiving no G-CSFs were 26–52% higher (depending on cancer type) for patients with a >80-min one-way travel time, compared to patients traveling <20-min. Concurrently, the odds of FN (using a “narrow” definition) were 18–93% higher for patients who did not receive G-CSFs in the first cycle of chemotherapy.</p> <p><b>Conclusions:</b> Travel burden, linked to clinic visits for G-CSF administration following myelosuppressive chemotherapy, is associated with sub-optimal use of G-CSF prophylaxis, which may result in a higher incidence of FN.</p

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis based on real-world data from 2010 to 2015

<p><b>Objective:</b> Evidence suggests that not all cancer chemotherapy patients who receive first-cycle pegfilgrastim prophylaxis (PP) continue to receive it in later cycles, and that these patients may be subsequently at higher risk of febrile neutropenia (FN). Available evidence, however, may not be reflective of current clinical practice. We undertook an evaluation to estimate the odds of FN, beginning with second chemotherapy cycle, among patients who received PP in that cycle and all previous cycles versus those who received PP in all previous cycles only, using recent real-world data.</p> <p><b>Methods:</b> A matched-cohort design and data from two US healthcare claims repositories (2010–2015) were employed. The source population comprised cancer patients who received intermediate/high-risk chemotherapy and first-cycle PP. From the source population, beginning with the second cycle, all patients who received PP in all previous cycles were identified. From this subset, patients who did not receive PP in the cycle of interest (“comparison patients”) were matched to those who received PP in that cycle (“PP patients”); the same process was repeated for subsequent cycles. Odds ratios (ORs) for FN (broad and narrow definitions) were estimated using generalized estimating equations.</p> <p><b>Results:</b> Among 47,254 patients in the source population, 9% did not receive second-cycle PP and were matched to those who did. FN odds in cycle 2 were significantly higher among comparison patients versus PP patients (OR [broad definition]: 1.7, <i>p</i> < .001); OR [narrow definition]: 4.3, <i>p</i> < .001). Results for subsequent cycles and for the last cycle, respectively, were comparable (OR [range, broad definition]: 1.6 to 3.1, <i>p</i> < .001 for all; OR [range, narrow definition]: 2.7 to 11.8, <i>p</i> < .001 for all).</p> <p><b>Conclusions:</b> In this real-world evaluation of cancer chemotherapy patients who received first-cycle PP, FN risk was substantially higher among patients who did not receive PP in subsequent cycles versus those who continued PP.</p

Risk of chemotherapy-induced febrile neutropenia by day of pegfilgrastim prophylaxis in US clinical practice from 2010 to 2015

<p><b>Objective:</b> Pegfilgrastim prophylaxis (PP) is recommended 1–3 days following administration of chemotherapy during the cycle. Some patients, however, receive PP before or after the recommended timing. While evidence suggests that risk of febrile neutropenia (FN) may be lower when PP is administered per recommendation, such evidence is based on older data. We undertook a new study to compare FN risk between patients who received PP on the last day of chemotherapy (“day 0”) or 4–5 days following chemotherapy (“days 4–5”), versus 1–3 days following chemotherapy (“days 1–3”), using recent data from US clinical practice.</p> <p><b>Methods:</b> A retrospective cohort design and data from two US private healthcare claims repositories (2010–2016) were employed. Patients received intermediate/high-risk chemotherapy regimens for solid tumors or non-Hodgkin’s lymphoma, and PP in ≥1 cycle; all cycles with PP were pooled for analyses. Adjusted odds ratios (OR) for FN during the cycle were estimated for patients who received PP on day 0 or days 4–5, vs. days 1–3, using generalized estimating equations.</p> <p><b>Results:</b> The study population included 53,814 patients who received PP in 217,273 cycles; in 9% of cycles, patients received PP on day 0 (8%) or days 4–5 (<1%). Odds of FN in cycle 1 were significantly higher among patients receiving PP on day 0 (OR: 1.4 [95% CI: 1.2–1.7]) or days 4–5 (1.9 [1.2–3.0]), vs. days 1–3, in that cycle. Results for subsequent cycles of chemotherapy were comparable to those for the first cycle.</p> <p><b>Conclusions:</b> In this large-scale retrospective evaluation of cancer chemotherapy patients receiving PP in recent US clinical practice, PP was administered before or after the recommended timing in 9% of cycles. FN incidence was significantly higher in these cycles providing additional real-world evidence that PP should be administered the day after chemotherapy in alignment with recently updated US practice guidelines.</p

Probability sensitivity analysis results using second-order Monte Carlo simulation (10,000 draws with 95% confidence interval ellipse, with A$50,000/QALY line).

<p>Probability sensitivity analysis results using second-order Monte Carlo simulation (10,000 draws with 95% confidence interval ellipse, with A$50,000/QALY line).</p

Summary of deterministic sensitivity analyses.

<p>Abbreviation: MTESS = mobile telemedicine-enabled screening and surveillance; ICER = Incremental cost effectiveness ratio. Note: Dominant = MTESS is the dominant strategy.</p><p>Summary of deterministic sensitivity analyses.</p

Costs for surgical treatment in outpatient clinic.

<p>Abbreviation: ACE = annual equivalent cost; ENT = ear, nose, throat; FTE = full time equivalent;</p><p>Costs for surgical treatment in outpatient clinic.</p

Transition probabilities.

<p>Abbreviation: MTESS = mobile telemedicine-enabled screening and surveillance;</p><p>Transition probabilities.</p

Utility weights.

<p>^aAverage of hearing loss and normal hearing in children</p><p>^bAverage of hearing loss and normal hearing in adult</p><p>Utility weights.</p

Risk of chemotherapy-induced febrile neutropenia with same-day versus next-day pegfilgrastim prophylaxis among patients aged ≥65 years: a retrospective evaluation using Medicare claims

<p><b>Background:</b> Two recent evaluations reported that risk of febrile neutropenia (FN) may be higher when pegfilgrastim prophylaxis (PP) is administered on same day as chemotherapy rather than per recommendation (1–3 days following chemotherapy). Such evidence is based largely on the experience of younger privately insured adults and may not be generalizable to older patients in US clinical practice.</p> <p><b>Methods:</b> A retrospective cohort design and data from Medicare Claims Research Identifiable Files (January 2008–September 2015) were employed. Patients were aged ≥65 years, had breast cancer or non-Hodgkin’s lymphoma, received chemotherapy with intermediate/high risk for FN, and received PP in ≥1 cycle; cycles with PP were stratified based on administration day (same-day [“Day 0”] vs. 1–3 days following chemotherapy [“Days 1–3”]) and were pooled for analyses. Adjusted odds ratios (ORs) for FN during the cycle were estimated for patients who received PP on Day 0 versus Days 1–3.</p> <p><b>Results:</b> Study population included 65,003 patients who received PP in 261,184 cycles; in 5% of cycles, patients received PP on Day 0. Incidence proportion for FN in cycle 1 was 11.4% for Day 0 versus 8.4% for Days 1–3; adjusted OR was 1.4 (<i>p</i> < .001). Incidence proportion for FN when considering all cycles was 7.7% for Day 0 and 6.0% for Days 1–3; adjusted OR was 1.3 (<i>p</i> < .001). Adjusted ORs when considering all cycles and only inpatient FN episodes (1.3, <i>p</i> < .001) and the narrow definition for FN (1.5, <i>p</i> < .001) were similar.</p> <p><b>Conclusions:</b> Among Medicare patients receiving chemotherapy and PP in US clinical practice, PP was administered before the recommended timing in 5% of cycles and FN incidence was significantly higher in these cycles. Along with prior research, study findings support recently updated US practice guidelines indicating that PP should be administered the day after chemotherapy.</p