-
Molecular and Clinical Oncology May 2022Combined treatment with bevacizumab and trifluridine/tipiracil (TAS-102) leads to an increased chance of survival in patients with refractory metastatic colorectal...
Prophylactic use of pegfilgrastim enables the management of severe neutropenia without dose delays in patients with metastatic colorectal cancer treated with TAS-102 plus bevacizumab.
Combined treatment with bevacizumab and trifluridine/tipiracil (TAS-102) leads to an increased chance of survival in patients with refractory metastatic colorectal cancer (mCRC); however, this treatment is associated with an increased frequency of severe neutropenia (number of neutrophils <1,000), which should ideally be managed without dose delays. The present study provided a retrospective review of 35 patients with mCRC, and aimed to elucidate the benefits of prophylactic pegfilgrastim for the treatment of severe neutropenia. Patients received TAS-102 (35 mg/m) orally twice daily on days 1-5 and 8-12 of each 28-day treatment cycle, along with intravenous bevacizumab (5 mg/kg) on days 1 and 15. Moreover, the patients received 3.6 mg pegfilgrastim on day 15 of each cycle. The incidence of adverse events (AEs), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were assessed. In the first and subsequent cycles, 23 and 12 patients, respectively, received pegfilgrastim. The most common AE experienced was grade 3/4 neutropenia (8 patients; 22.9%). Among these 8 patients, 6 (17.1%) and 3 (8.6%) exhibited neutropenia prior to receiving pegfilgrastim or following discontinuation of pegfilgrastim administration, respectively. Moreover, 1 individual among these 8 patients (2.9%) demonstrated grade 3 neutropenia both prior to receiving pegfilgrastim and following discontinuation of pegfilgrastim. A total of 2 patients (5.7%) exhibited grade 3 bone pain, which prevented sustainable administration of pegfilgrastim and resulted in grade 3 neutropenia. Dose delays and dose reduction of TAS-102 due to neutropenia were required in 5 (14.3%) and 2 (5.7%) patients, respectively, during the treatment period. None of the patients exhibited severe neutropenia during chemotherapy after pegfilgrastim administration, thereby preventing dose delays and dose reduction of TAS-102. The relative dose intensity was 96.8% (65.0-100.0%), and the DCR was 54.3%. The median PFS and median OS were 4.4 and 14.9 months, respectively. In conclusion, prophylactic pegfilgrastim may facilitate the management of severe neutropenia without dose delays in patients with mCRC treated with TAS-102 plus bevacizumab.
PubMed: 35463210
DOI: 10.3892/mco.2022.2536 -
Oncology and Therapy Dec 2022Granulocyte colony-stimulating factor (G-CSF) biologics, such as pegfilgrastim, are a standard of care in supportive cancer treatment that are administered once per... (Review)
Review
Granulocyte colony-stimulating factor (G-CSF) biologics, such as pegfilgrastim, are a standard of care in supportive cancer treatment that are administered once per chemotherapy cycle to reduce the incidence of febrile neutropenia. The high cost of these biologics in the United States can be a limiting factor to accessing care; however, lower-cost pegfilgrastim biosimilars have been available for several years for patients requiring prophylaxis of febrile neutropenia. Different options for pegfilgrastim administration are also now available to accommodate specific patient preferences. As patients may want to minimize the risk of both neutropenia and SARS-CoV-2 infection, same-day administration is a pertinent option during the present COVID-19 pandemic. Therefore, individualized, patient-centered approaches and risk-management strategies should be considered when selecting the treatment and administration method for prophylaxis of febrile neutropenia. Three methods of administration would minimize hospital or clinic visits while also providing the prophylactic effect of G-CSF: same-day administration after chemotherapy, use of the US Food and Drug Administration-approved on-body injector delivering pegfilgrastim approximately 27 h after chemotherapy, or self-administration by the patient or caregiver > 24 h after chemotherapy. Choice of the specific administration option should be based on the patient's specific needs, while also considering mitigating factors, such as the economic burden associated with biologic medications and the risk of COVID-19. Pegfilgrastim biosimilars can minimize the additional financial burden on patients and the health care system during this pandemic and beyond.
PubMed: 36114331
DOI: 10.1007/s40487-022-00207-2 -
Journal of Medical Economics Dec 2020In this pharmacoeconomic simulation, we: (1) modeled the cost-efficiency of converting patients from reference pegfilgrastim to biosimilar pegfilgrastim-cbqv for...
Cost-efficiency and expanded access of prophylaxis for chemotherapy-induced (febrile) neutropenia: economic simulation analysis for the US of conversion from reference pegfilgrastim to biosimilar pegfilgrastim-cbqv.
AIMS
In this pharmacoeconomic simulation, we: (1) modeled the cost-efficiency of converting patients from reference pegfilgrastim to biosimilar pegfilgrastim-cbqv for prophylaxis of chemotherapy-induced (febrile) neutropenia (CIN/FN) from the US payer perspective, (2) simulated how savings enable, on a budget-neutral basis, expanded access to pegfilgrastim-cbqv, and (3) estimated the number-needed-to-convert (NNC) to purchase one additional dose of pegfilgrastim-cbqv.
METHODS
In a hypothetical panel of 20,000 patients, we modeled cost-savings utilizing: two reference formulations (pre-filled syringe [PFS] and on-body injector [OBI]), three medication cost inputs (average sales price [ASP], wholesale acquisition cost [WAC], and an age-proportionate blended ASP/WAC rate), administration cost for injection (PFS) and device application (OBI), conversion rates of 10-100%, and 1-6 cycles of prophylaxis. Cost-savings were used to estimate additional doses of pegfilgrastim-cbqv that could be purchased and the NNC to purchase one additional dose.
RESULTS
Using ASP and 10% conversion from reference OBI to pegfilgrastim-cbqv, savings range from $326,744 (1 cycle) to $2.0M (6 cycles) which could provide 93-556 additional doses of pegfilgrastim-cbqv, respectively; the NNC to purchase one additional dose of pegfilgrastim-cbqv ranges from 21.6 (1 cycle) down to 3.6 patients (6 cycles). The WAC model saves $41.1M per cycle and $246.7M over 6 cycles at 100% conversion from reference PFS which could provide 9,709-58,253 additional pegfilgrastim-cbqv doses; the NNC ranges from 2.1 (1 cycle) to 0.3 (6 cycles). Using the blended ASP/WAC rate, converting 50% from reference OBI to pegfilgrastim-cbqv would save $10.2M per cycle and $60.9M over 6 cycles providing 2,638-15,829 additional doses of pegfilgrastim-cbqv; NNCs are 3.8 (1 cycle) and 0.6 patients (6 cycles).
CONCLUSIONS
Converting 20,000 patients from reference to pegfilgrastim-cbqv over 6 cycles can generate savings up to $246.7M, enough to purchase up to 58,253 additional doses of pegfilgrastim-cbqv. This simulation provides economic justification for prophylaxis with biosimilar pegfilgrastim-cbqv.
Topics: Antineoplastic Agents; Biosimilar Pharmaceuticals; Filgrastim; Humans; Neutropenia; Polyethylene Glycols
PubMed: 33023360
DOI: 10.1080/13696998.2020.1833339 -
Cancer Treatment and Research... 2021Evidence-based US guidelines provide recommendations for the use of granulocyte colony-stimulating factor (G-CSF) as supportive therapy in patients with cancer receiving... (Review)
Review
Evidence-based US guidelines provide recommendations for the use of granulocyte colony-stimulating factor (G-CSF) as supportive therapy in patients with cancer receiving chemotherapy. Pegfilgrastim is recommended for FN prophylaxis in patients with non-myeloid malignancies receiving a high-risk chemotherapy regimen, or an intermediate-risk regimen if one or more risk factors are present. The guidelines highlight the patient characteristics and chemotherapy regimens for solid tumors and hematologic malignancies that may influence a patient's overall risk of FN and may benefit from pegfilgrastim support. This review aimed to evaluate how pegfilgrastim use in patients with cancer receiving myelosuppressive chemotherapy in routine clinical practice aligns with evidence-based US guidelines. Examination of the literature revealed widespread deviation in relation to under- and over-prescribing, and timing of administration in US clinical practice. Pegfilgrastim is often over-prescribed in patients receiving palliative chemotherapy and those at low risk of FN. Potential under-prescribing of pegfilgrastim was also observed. In this literature search, data that appear to support same-day administration of pegfilgrastim were from uncontrolled studies that were limited in size. Analyses of healthcare claims data clearly favored next-day use, with statistically significant increases in FN incidence among patients receiving same-day pegfilgrastim versus those treated 1-4 days post-chemotherapy. Earlier-than-recommended administration typically occurs at the physician's discretion where next-day administration might present barriers to the patient receiving supportive therapy.There is a need to ensure appropriate prescribing to optimize patient outcomes, as deviation from the guideline recommendations was associated with increased incidence of FN and hospitalization.
Topics: Filgrastim; Guideline Adherence; Humans; Medication Adherence; Neutropenia; Polyethylene Glycols; United States
PubMed: 34655862
DOI: 10.1016/j.ctarc.2021.100466 -
Supportive Care in Cancer : Official... Jan 2024Evaluate the safety and efficacy of efbemalenograstim alfa for neutrophil support in breast cancer patients undergoing myelosuppressive chemotherapy in a phase 2,... (Randomized Controlled Trial)
Randomized Controlled Trial
Efbemalenograstim alfa not inferior to pegfilgrastim in providing neutrophil support in women with breast cancer undergoing myelotoxic chemotherapy: results of a phase 2 randomized, multicenter, open-label trial.
PURPOSE
Evaluate the safety and efficacy of efbemalenograstim alfa for neutrophil support in breast cancer patients undergoing myelosuppressive chemotherapy in a phase 2, dose-finding, open-label study (NCT01648322, ClinicalTrials.gov, 2012-07-19).
METHODS
232 patients received up to 4 cycles of chemotherapy, 141 patients with docetaxel + cyclophosphamide (TC) and 91 patients with docetaxel + doxorubicin + cyclophosphamide (TAC). Patients were randomized to efbemalenograstim alfa (80, 240, or 320 µg/kg [TC]; 240 or 320 µg/kg [TAC]) or pegfilgrastim (6 mg) on Day 2 of each cycle.
RESULTS
Efbemalenograstim alfa was non-inferior to pegfilgrastim in duration of moderate and severe neutropenia (absolute neutrophil count [ANC] < 1.0 × 10/L) in TAC Cycle 1 (mean [SD] of 2.1 [1.58] and 2.1 [1.46] days for 240 µg/kg and 320 µg/kg efbemalenograstim alfa, respectively, and 1.8 [1.28] days for pegfilgrastim), with a difference (95% CI) of 0.3 (-0.4, 1.1) days. ANC nadir occurred between Days 7-8 of TAC Cycle 1, with mean [SD] of 0.68 [1.064], 0.86 [1.407] and 0.78[1.283] × 10/L for 240 µg/kg, 320 µg/kg efbemalenograstim alfa and pegfilgrastim, respectively. Time to ANC recovery post nadir (defined as an ANC > 2.0 × 10/L after the expected ANC nadir) was 2.0-2.4 and 1.9 days for TAC patients treated with efbemalenograstim alfa and pegfilgrastim, respectively. No significant difference was found between any dose of efbemalenograstim alfa and pegfilgrastim in TAC Cycle 1 for incidence of moderate to severe neutropenia (76%-77% of patients) or incidence of severe neutropenia (ANC < 0.5 × 10/L; 63%-72%). Efbemalenograstim alfa exhibited similar safety profile to pegfilgrastim. Febrile neutropenia occurred in 4 (1.8%) patients, 2 patients each for 320 µg/kg efbemalenograstim alfa and pegfilgrastim, with no event considered related to study drug.
CONCLUSION
Efbemalenograstim alfa was comparable to pegfilgrastim in efficacy and safety.
GOV IDENTIFIER
NCT01648322.
Topics: Humans; Female; Neutrophils; Breast Neoplasms; Docetaxel; Neutropenia; Cyclophosphamide
PubMed: 38194162
DOI: 10.1007/s00520-023-08260-x -
Frontiers in Oncology 2021It has been reported that chemotherapy drugs and granulocyte colony-stimulating factor (G-CSF) administered on the same day can aggravate neutropenia. In the present...
It has been reported that chemotherapy drugs and granulocyte colony-stimulating factor (G-CSF) administered on the same day can aggravate neutropenia. In the present study, we investigated the safety of pegfilgrastim during bleomycin, etoposide, and cisplatin (BEP) therapy. This single-center retrospective study, including 137 cycles of BEP therapy for germ cell tumors between January 2008 and April 2021, investigated safety. Short-acting G-CSF was used for 84 cycles and pegfilgrastim was used for 53 cycles. In the pegfilgrastim group, neutrophil count at nadir was significantly higher than in the G-CSF group (median 1,650/μl and 680/μl, respectively). The incidence of grade 3-4 neutropenia was significantly higher and the duration longer in the G-CSF group. Also, there was no significant difference in the incidence of febrile neutropenia. In conclusion, concomitant use of pegfilgrastim during BEP therapy did not increase neutropenia and was effective in terms of safety.
PubMed: 35070973
DOI: 10.3389/fonc.2021.770067 -
Case Reports in Oncological Medicine 2022Checkpoint inhibitors (CPIs) and pegfilgrastim, a long-acting growth factor agent, are vital components of current cancer treatments. Immune-related adverse events...
Checkpoint inhibitors (CPIs) and pegfilgrastim, a long-acting growth factor agent, are vital components of current cancer treatments. Immune-related adverse events (irAEs) such as colitis and pneumonitis are well-established toxicities associated with CPI therapy. However, large-vessel vasculitis secondary to CPI utilization is reported only in rare case reports and case series. Interestingly, large-vessel vasculitis has also been reported as a rare complication of pegfilgrastim use. We present a 59-year-old female with left stage IIA (cT2N0M0) triple-negative breast cancer receiving neoadjuvant decitabine and pembrolizumab prior to neoadjuvant chemotherapy (NAC). NAC included standard-of-care dose dense doxorubicin and cyclophosphamide (ddAC) supported with pegfilgrastim use followed by weekly carboplatin and paclitaxel. After receiving her second cycle of ddAC with pegfilgrastim, the patient reported five days of left shoulder and arm pain. Subsequent CT imaging demonstrated wall thickening and inflammatory changes surrounding the left subclavian artery, aortic arch, left carotid artery, proximal innominate arteries, and the mid internal carotid arteries and its branching vessels. These findings were extremely concerning for large-vessel vasculitis. Excluding CPI therapy and pegfilgrastim use, no additional inciting event or medication that the patient was exposed to was noted to be associated with large-vessel vasculitis. We present this case to report on this rare but severe complication from commonly utilized agents in cancer treatment. We also extend the possibility of large-vessel vasculitis development in relation to the COVID-19 vaccine due to shared ingredients found in both the vaccine and pegfilgrastim. It is important to outline the treatment used for such a complication as no standardized treatment has been established for large-vessel vasculitis caused by CPI therapy or pegfilgrastim use.
PubMed: 35251725
DOI: 10.1155/2022/7295305 -
Le Infezioni in Medicina Mar 2020Not available.
Not available.
Topics: Antineoplastic Agents; Febrile Neutropenia; Filgrastim; Granulocyte Colony-Stimulating Factor; Guideline Adherence; Hematologic Agents; Humans; Neoplasms; Neutropenia; Polyethylene Glycols
PubMed: 32172272
DOI: No ID Found -
World Journal of Surgical Oncology Jul 2019The docetaxel, 5-fluorouracil, and cisplatin (DCF) regimen is an effective form of chemotherapy for advanced esophageal cancer. However, the incidence of adverse events... (Clinical Trial)
Clinical Trial
Risk factors for febrile neutropenia and effectiveness of primary prophylaxis with pegfilgrastim in patients with esophageal cancer treated with docetaxel, cisplatin, and 5-fluorouracil.
BACKGROUND
The docetaxel, 5-fluorouracil, and cisplatin (DCF) regimen is an effective form of chemotherapy for advanced esophageal cancer. However, the incidence of adverse events such as febrile neutropenia and hematological toxicity is high.
METHODS
Among 937 patients with esophageal cancer at Toranomon Hospital between January 2011 and December 2018, 92 who underwent the DCF regimen as initial treatment were selected. We investigated the risk factors for febrile neutropenia in patients with esophageal cancer treated with DCF regimen and the effectiveness of pegfilgrastim as primary prophylaxis.
RESULTS
Adverse events (CTCAE grade ≥ 3) were observed in 45 of the 92(48.9%) patients with esophageal cancer treated with an initial DCF regimen. Febrile neutropenia was observed in 20 (21.7%) patients. Non-use of pegfilgrastim (odds ratio = 16.393; 95% confidence interval 2.049-125.0) as primary prophylaxis was identified as an independent factor predictive of febrile neutropenia. The pegfilgrastim group had a significantly lower incidence of neutropenia than the control group (9.1% vs 61.0%; p < 0.001). The incidence of febrile neutropenia was 3.0% in the pegfilgrastim group and 32.2% in the control group (p = 0.001). In addition, the incidence of any adverse effect ≥ CTCAE grade3 was also significantly lower in the pegfilgrastim group (12.1% vs 69.5%; p < 0.001). The reduced/interruption rate of next DCF therapy was 6.1% in the pegfilgrastim group and 30.5% in the control group (p = 0.006).
CONCLUSION
This study revealed that the non-use of pegfilgrastim was an independent factor predictive of febrile neutropenia in multivariate analysis. Pegfilgrastim as primary prophylaxis prevents severe neutropenia and febrile neutropenia in patients with esophageal cancer treated with the DCF regimen.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Esophageal Neoplasms; Febrile Neutropenia; Female; Filgrastim; Fluorouracil; Follow-Up Studies; Humans; Male; Middle Aged; Polyethylene Glycols; Prognosis; Retrospective Studies; Risk Factors; Survival Rate
PubMed: 31315622
DOI: 10.1186/s12957-019-1665-x -
Cancer Medicine Journal Apr 2021Pegfilgrastim is typically administered 24 hours after chemotherapy per package insert; however some patients are unable or unwilling to return for this additional visit...
BACKGROUND
Pegfilgrastim is typically administered 24 hours after chemotherapy per package insert; however some patients are unable or unwilling to return for this additional visit due to work or transportation especially with regimens consisting of infusional 5-FU. Same-day dosing eliminates need for this additional visit. Results from prior studies in other tumor types are inconclusive as few support same-day dosing whereas others show inferiority. Purpose of our study was to determine safety and efficacy of administering pegfilgrastim on same day as chemotherapy in patients with gastrointestinal (GI) malignancies.
METHOD
A single-institution retrospective review was conducted of 69 patients with GI malignancies who received chemotherapy and same-day pegfilgrastim (6 mg) within 1 hour of completion of chemotherapy from Jan 2014 through Jan 2017. As per institutional guidelines, patients were counseled on risks of same-day pegfilgrastim prior to its administration. These patients were compared with a set of 70 patients who received pegfilgrastim 24-hours after completing the chemotherapy for GI cancers.
RESULT
A total of 536 chemotherapy cycles in 69 patients were analyzed. Median absolute neutrophil count nadir for all cycles was 4538/uL (Range: 1160 - 25168). Grade 1 and 2 neutropenia developed in 6 of 536 (1%) cycles. Bone pain reported in 3 patients (4%). There were no episodes of grade 3 or 4 neutropenia or febrile neutropenia. None had dose reductions, chemotherapy delays, hospitalizations, or antibiotic use due to neutropenia.
CONCLUSION
We believe our study is the first in GI malignancies to report that same-day pegfilgrastim administration may be as effective and safe as next-day administration, benefiting patients and might reduce costs.
PubMed: 32656544
DOI: No ID Found