The risk of febrile neutropenia and need for G-CSF primary prophylaxis with the docetaxel and cyclophosphamide regimen in early-stage breast cancer patients: a meta-analysis
Abstract:The febrile neutropenia (FN) rates reported with the docetaxel 75 mg/m(2) plus cyclophosphamide 600 mg/m(2) (TC) regimen given every 3 weeks vary from 4 to 69 % in early-stage breast cancer (ESBC) patients. This creates uncertainty as to whether patients receiving the TC regimen should also receive granulocyte colony-stimulating factor primary prophylaxis (G-CSFpp), which is recommended when chemotherapy regimens have ≥20 % FN rate. We conducted a meta-analysis of published studies to determine FN rate with th… Show more
“…Results from the analyses based on an alternative data source for the disutility of FN and with discount rates ranging from 0 to 3% were similar to the base case. Using an alternative data source for the probability of FN for the TC regimen [47] resulted in an increase in the ICER for PP with pegfilgrastim (vs. SP with pegfilgrastim) from €15,500 to €24,100 per QALY.Fig. 2Deterministic and probabilistic sensitivity analyses.…”
Section: Resultsmentioning
confidence: 99%
“…For DSAs, key model parameters were varied using 95% confidence intervals (CIs), standard errors, and plausible ranges derived from published literature (Tables 1, 2) to assess how univariate changes in key model parameters and parameter uncertainty impacted cost-effectiveness results. In addition to the DSAs, a scenario analysis was performed using an alternative data source for the baseline risk of FN (23.2%) [47]. …”
ObjectiveThe objective of this study was to evaluate the cost effectiveness of no prophylaxis, primary prophylaxis (PP), or secondary prophylaxis (SP) with granulocyte colony-stimulating factors (G-CSFs), i.e., pegfilgrastim, lipegfilgrastim, filgrastim (6- and 11-day), or lenograstim (6- and 11-day), to reduce the incidence of febrile neutropenia (FN) in patients with stage II breast cancer receiving TC (docetaxel, cyclophosphamide) and in patients with non-Hodgkin lymphoma (NHL) receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) over a lifetime horizon from a Belgian payer perspective.MethodsA Markov cycle tree tracked FN events during chemotherapy (3-week cycles) and long-term survival (1-year cycles). Model inputs, including the efficacy of each strategy, risk of reduced relative dose intensity (RDI), and the impact of RDI on mortality, utilities, and costs (in €; 2014 values) were estimated from public sources and the published literature. Incremental cost-effectiveness ratios (ICERs) were assessed for each strategy for costs per FN event avoided, life-year (LY) saved, and quality-adjusted LY (QALY) saved. LYs and QALYs saved were discounted at 1.5% annually. Deterministic and probabilistic sensitivity analyses (DSAs and PSAs) were conducted.ResultsBase-case ICERs for PP with pegfilgrastim relative to SP with pegfilgrastim were €15,500 per QALY and €14,800 per LY saved for stage II breast cancer and €7800 per QALY and €6900 per LY saved for NHL; other comparators were either more expensive and less effective than PP or SP with pegfilgrastim or had lower costs but higher ICERs (relative to SP with pegfilgrastim) than PP with pegfilgrastim. Results of the DSA for breast cancer and NHL comparing PP and SP with pegfilgrastim indicate that the model results were most sensitive to the cycle 1 risk of FN, the proportion of FN events requiring hospitalization, the relative risk of FN in cycles ≥2 versus cycle 1, no history of FN, and the mortality hazard ratio for RDI (<90% vs ≥90% [for NHL]). In the PSAs for stage II breast cancer and NHL, the probabilities that PP with pegfilgrastim was cost effective or dominant versus all other prophylaxis strategies at a €30,000/QALY willingness-to-pay threshold were 52% (other strategies ≤24%) and 58% (other strategies ≤24%), respectively.ConclusionFrom a Belgian payer perspective, PP with pegfilgrastim appears cost effective compared to other prophylaxis strategies in patients with stage II breast cancer or NHL at a €30,000/QALY threshold.Electronic supplementary materialThe online version of this article (doi:10.1007/s40273-016-0474-0) contains supplementary material, which is available to authorized users.
“…Results from the analyses based on an alternative data source for the disutility of FN and with discount rates ranging from 0 to 3% were similar to the base case. Using an alternative data source for the probability of FN for the TC regimen [47] resulted in an increase in the ICER for PP with pegfilgrastim (vs. SP with pegfilgrastim) from €15,500 to €24,100 per QALY.Fig. 2Deterministic and probabilistic sensitivity analyses.…”
Section: Resultsmentioning
confidence: 99%
“…For DSAs, key model parameters were varied using 95% confidence intervals (CIs), standard errors, and plausible ranges derived from published literature (Tables 1, 2) to assess how univariate changes in key model parameters and parameter uncertainty impacted cost-effectiveness results. In addition to the DSAs, a scenario analysis was performed using an alternative data source for the baseline risk of FN (23.2%) [47]. …”
ObjectiveThe objective of this study was to evaluate the cost effectiveness of no prophylaxis, primary prophylaxis (PP), or secondary prophylaxis (SP) with granulocyte colony-stimulating factors (G-CSFs), i.e., pegfilgrastim, lipegfilgrastim, filgrastim (6- and 11-day), or lenograstim (6- and 11-day), to reduce the incidence of febrile neutropenia (FN) in patients with stage II breast cancer receiving TC (docetaxel, cyclophosphamide) and in patients with non-Hodgkin lymphoma (NHL) receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) over a lifetime horizon from a Belgian payer perspective.MethodsA Markov cycle tree tracked FN events during chemotherapy (3-week cycles) and long-term survival (1-year cycles). Model inputs, including the efficacy of each strategy, risk of reduced relative dose intensity (RDI), and the impact of RDI on mortality, utilities, and costs (in €; 2014 values) were estimated from public sources and the published literature. Incremental cost-effectiveness ratios (ICERs) were assessed for each strategy for costs per FN event avoided, life-year (LY) saved, and quality-adjusted LY (QALY) saved. LYs and QALYs saved were discounted at 1.5% annually. Deterministic and probabilistic sensitivity analyses (DSAs and PSAs) were conducted.ResultsBase-case ICERs for PP with pegfilgrastim relative to SP with pegfilgrastim were €15,500 per QALY and €14,800 per LY saved for stage II breast cancer and €7800 per QALY and €6900 per LY saved for NHL; other comparators were either more expensive and less effective than PP or SP with pegfilgrastim or had lower costs but higher ICERs (relative to SP with pegfilgrastim) than PP with pegfilgrastim. Results of the DSA for breast cancer and NHL comparing PP and SP with pegfilgrastim indicate that the model results were most sensitive to the cycle 1 risk of FN, the proportion of FN events requiring hospitalization, the relative risk of FN in cycles ≥2 versus cycle 1, no history of FN, and the mortality hazard ratio for RDI (<90% vs ≥90% [for NHL]). In the PSAs for stage II breast cancer and NHL, the probabilities that PP with pegfilgrastim was cost effective or dominant versus all other prophylaxis strategies at a €30,000/QALY willingness-to-pay threshold were 52% (other strategies ≤24%) and 58% (other strategies ≤24%), respectively.ConclusionFrom a Belgian payer perspective, PP with pegfilgrastim appears cost effective compared to other prophylaxis strategies in patients with stage II breast cancer or NHL at a €30,000/QALY threshold.Electronic supplementary materialThe online version of this article (doi:10.1007/s40273-016-0474-0) contains supplementary material, which is available to authorized users.
“…Docetaxel is a commonly used anti-cancer agent [ 5 – 7 ] that possess pronounced myelosuppressive properties [ 8 ], which exposes the patient to a high risk for severe neutropenia and consequently life-threatening conditions such as febrile neutropenia (FN). Docetaxel, typically administered as a 1 h infusion every 3 weeks in multiple cycles depending on the cancer type, can cause high rates (>20%) of FN [ 9 ]. Prior to each administration of cytotoxic drugs, the absolute neutrophil count (ANC) is measured to confirm adequate levels, i.e.…”
PurposeTo investigate whether a more frequent monitoring of the absolute neutrophil counts (ANC) during myelosuppressive chemotherapy, together with model-based predictions, can improve therapy management, compared to the limited clinical monitoring typically applied today.MethodsDaily ANC in chemotherapy-treated cancer patients were simulated from a previously published population model describing docetaxel-induced myelosuppression. The simulated values were used to generate predictions of the individual ANC time-courses, given the myelosuppression model. The accuracy of the predicted ANC was evaluated under a range of conditions with reduced amount of ANC measurements.ResultsThe predictions were most accurate when more data were available for generating the predictions and when making short forecasts. The inaccuracy of ANC predictions was highest around nadir, although a high sensitivity (≥90%) was demonstrated to forecast Grade 4 neutropenia before it occurred. The time for a patient to recover to baseline could be well forecasted 6 days (±1 day) before the typical value occurred on day 17.ConclusionsDaily monitoring of the ANC, together with model-based predictions, could improve anticancer drug treatment by identifying patients at risk for severe neutropenia and predicting when the next cycle could be initiated.Electronic supplementary materialThe online version of this article (doi:10.1007/s00280-017-3366-x) contains supplementary material, which is available to authorized users.
“…Granulocyte colony-stimulating factors (G-CSF) have been introduced to clinical practice to prevent or to treat neutropenia. G-CSF has proven to be highly effective in decreasing the number of FN incidents and neutropeniarelated infections as well as in shortening the duration of neutropenia [5]. As a result, antibiotics usage is decreased and sub-optimal dosing of chemotherapy is avoided.…”
mentioning
confidence: 99%
“…As a result, antibiotics usage is decreased and sub-optimal dosing of chemotherapy is avoided. G-CSF is now highly recommended, as it significantly reduces the early mortality rate [5]. G-CSF administration is currently strongly advised when patients receive chemotherapy associated with high (estimated as greater than 20%) risk of FN.…”
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