Biosimilar medicines in oncology: Single-center experience with biosimilar G-CSF.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19501-e19501
Author(s):  
Nello Salesi ◽  
Barbara Di Cocco ◽  
Enzo Veltri

e19501 Background: A biosimilar medicine is one with proven similarity to a reference biological product for which the patent has expired and whose active ingredient is produced or derived from a living organism. Recombinant granulocyte colony-stimulating growth factors (G-CSF) are used for the prophylaxis of febrile neutropenia. Methods: In this observational study a total of 48 patients with solid tumours were treated with biosimilar Zarzio, a new biosimilar G-CSF for 4−14 days from the day following the end of chemotherapy. The primary prophylaxis group was composed of 10 patients with breast carcinoma receiving adjuvant chemotherapy (CEF: 5-fluorouracil 600 mg/m2, epirubicin 100 mg/m2 G1, cyclophosphamide 600 mg/m2 G1, q 21 for 4 cycles à docetaxel 100 mg/m2 G1, q 21); 17 patients with locally advanced or metastatic lung carcinoma (66% adenocarcinoma, 34% squamous) receiving 4–6 cycles of platinum-based chemotherapy; 6 patients with metastatic gastric adenocarcinoma treated with TCF (Taxotere 75 mg/m2, cisplatin 75 mg/m2, 5-fluorouracil 300 mg/m2 by continuous 24 hour infusion for 5 days, q 21) for 4–6 cycles; 4 patients with prostate adenocarcinoma treated with Docetaxel 75 mg/m2 G1, q 21 in 6 cycles. The secondary prophylaxis group was composed of 11 patients with colorectal adenocarcinoma (54.5% treated with adjuvant XELOX therapy: Xeloda 2000 mg/m2 G1à14, oxaliplatin 130 mg/m2 G1, q 21, and the remainder treated with first-line metastatic FOLFOXIRI therapy [CPT-11 165mg/m2 G1, 5-FU 3200 mg/m2 continuous infusion for 48 hours, oxaliplatin 85 mg/m2 G1, q 14]). Results: Three cases of febrile neutropenia were reported: two in patients with prostate adenocarcinoma and one case in a patient with pulmonary squamous cell carcinoma and multiple secondary skeletal lesions. These patients were treated with antibiotics with resolution of the clinical picture without hospitalization after 24 hours. Conclusions: Our experience indicates that the use of biosimilar G-CSF is safe and effective at reducing neutropenic complications in patients with mixed tumors and is associated with cost savings.

Author(s):  
Claudio Cerchione ◽  
Davide Nappi ◽  
Giovanni Martinelli

AbstractMultiple myeloma (MM) survival rates have been substantially increased thanks to novel agents that have improved survival outcomes and shown better tolerability than treatments of earlier years. These new agents include immunomodulating imide drugs (IMiD) thalidomide and lenalidomide, the proteasome inhibitor bortezomib (PI), recently followed by new generation IMID pomalidomide, monoclonal antibodies daratumumab and elotuzumab, and next generation PI carfilzomib and ixazomib. However, even in this more promising scenario, febrile neutropenia remains a severe side effect of antineoplastic therapies and can lead to a delay and/or dose reduction in subsequent cycles. Supportive care has thus become key in helping patients to obtain the maximum benefit from novel agents. Filgrastim is a human recombinant subcutaneous preparation of G-CSF, largely adopted in hematological supportive care as “on demand” (or secondary) prophylaxis to recovery from neutropenia and its infectious consequences during anti-myeloma treatment. On the contrary, pegfilgrastim is a pegylated long-acting recombinant form of granulocyte colony-stimulating factor (G-CSF) that, given its extended half-life, can be particularly useful when adopted as “primary prophylaxis,” therefore before the onset of neutropenia, along chemotherapy treatment in multiple myeloma patients. There is no direct comparison between the two G-CSF delivery modalities. In this review, we compare data on the two administrations’ modality, highlighting the efficacy of the secondary prophylaxis over multiple myeloma treatment. Advantage of pegfilgrastim could be as follows: the fixed administration rather than multiple injections, reduction in neutropenia and febrile neutropenia rates, and, finally, a cost-effectiveness advantage.


2019 ◽  
Vol 26 (2) ◽  
pp. 428-433
Author(s):  
Elahe Laali ◽  
Jinous Fazli ◽  
Sanambar Sadighi ◽  
Mehdi Mohammadi ◽  
Kheirollah Gholami ◽  
...  

Introduction Febrile neutropenia (FN) is one of the dose-limiting adverse effects of chemotherapy. Granulocyte-Colony Stimulating Factors (G-CSFs) minimize the incidence of FN and reduce the risk of neutropenia complications. This study was conducted to address the prescription pattern of G-CSF for primary prophylaxis of FN during the first cycle of chemotherapy in solid tumors. Method This prospective observational study was done to investigate the G-CSF prescription pattern in patients receiving the first cycle of chemotherapy for solid tumors and compare it with the NCCN guideline recommendations. Result Based on the guideline, prophylactic G-CSF administration was indicated in 26 of the 96 patients (27.1%) and all of them received G-CSF. On the other hand, 70 patients (72.9%) did not meet the guideline criteria for prophylaxis, but 60 (62.5%) of them received G-CSF. Seven doses of pegfilgrastim and 165 doses of filgrastim were used inappropriately in the study population, which was associated with an economic burden of about 224.7 million IRR (5350 USD). Conclusion Taken together, inconsistencies with the guideline were observed in this prospective evaluation, suggesting that submitting rationalized policies to decrease G-CSF prescription, especially in patients with a lower or intermediate FN risk, yields substantial cost savings.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4263-4263
Author(s):  
D. Almenar ◽  
J. Mayans ◽  
O. Juan ◽  
J.M. García Bueno ◽  
Ji Jalón ◽  
...  

Abstract Background: Daily G-CSFs(Filgrastim, lenograstim) are widely used to reduce duration of chemotherapy-induced neutropenia(CIN) and incidence of febrile neutropenia(FN) in cancer patients(pts). Data on their patterns of use and effectiveness in routine clinical practice are however limited. The introduction of the once-per-cycle G-CSF pegfilgrastim(Neulasta®) in Spain in 2003 may have changed patterns of use of daily G-CSFs and CIN-related outcomes. Methods: Multicentre, retrospective, observational study of daily G-CSF and pegfilgrastim patterns of use and outcomes in adult subjects with non-myeloid malignancies receiving myelosuppressive chemotherapy(CT). Consecutive patient medical records with documented use of daily G-CSF or pegfilgrastim were abstracted from 10 Spanish centers during 2003. Endpoints: percentage of proactive(primary prophylaxis) vs reactive(secondary prophylaxis/treatment) use of G-CSFs, duration of treatment with G-CSF, and CIN-related outcomes(dose delay, dose reduction, incidence of FN, hospitalization and antibiotic consumption). Results: 248 charts documented pegfilgrastim or daily G-CSF use; 75 pts received pegfilgrastim only; 111 pts received daily G-CSF only(99 Filgrastim, 12 lenograstim); 62 pts received both daily G-CSF and pegfilgrastim during their CT(data not shown). Most common tumor types were lung(25%), breast(20%), malignant lymphomas(20%). Pattern of use (% pts on primary or secondary prophylaxis, or treatment at any time during CT) was:pegfilgrastim(39%,48%,17%, respectively) vs daily G-CSF(40%,48%,30%, respectively). Median number of injections/cycle in the daily G-CSF group was 6 (range 1–13) in primary prophylaxis, and 5 (range 1–11) in secondary prophylaxis and treatment. CIN-related outcomes are shown in the table below. Conclusions: Patterns of use of daily G-CSFs and pegfilgrastim were similar for primary and secondary prophylaxis, but a potential trend to less frequent treatment use in the pegfilgrastim group was observed. CIN-related complications, including incidence of FN, were observed to be lower in pts receiving pegfilgrastim. CT-related complications% pts (95% CI) Pegfilgrastim(n=75) Daily G-CSF(n=111) Dose Delay 44% (33; 55) 46% (36; 55) Dose Reduction 14.7% (8.2; 24.6) 20.7% (14.2; 29.2) Dose Reduction due to Neutropenia 6.7% (2.5; 15.0) 20.7% (14.1; 29.2) Febrile Neutropenia (FN) 10.7% (5.3; 19.9) 24.3% (17.2; 33.1) Hospitalization due to FN 9.3% (4.3; 18.3) 19.8% (13.4; 28.3) Antibiotic Consumption due to FN 8.0% (3.4; 16.7) 17.1% (11.2; 25.3)


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5353-5353
Author(s):  
Logan Moore ◽  
Trace Bartels ◽  
Daniel O. Persky ◽  
Abhijeet Kumar ◽  
Ivo Abraham ◽  
...  

Introduction: Granulocyte stimulating growth factors (G-CSF) such as filgrastim or pegfilgrastim are indicated as prophylaxis of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). BR regimen is considered an intermediate FN risk (10-20%) per National Comprehensive Cancer Network guidelines. Therefore, patients receiving BR need to be assessed using patient specific risk factors to evaluate the need for primary prophylaxis. This study evaluates real-world patterns and outcomes associated with primary and secondary G-CSF prophylaxis in patients with B-cell lymphoma and CLL treated with BR. Methods: Retrospective chart review of all lymphoma or CLL patients treated with BR from 11/2013 through 6/2019 at the University of Arizona Cancer Center was conducted. Baseline demographic and chemotherapy cycle data was analyzed through Chi-Squared test and Unpaired t-test with a-priori p-value of 0.05 being considered statistically significant. Results: Eighty-five patients met inclusion criteria. Of these, 48 received G-CSF during all chemotherapy cycles for primary prophylaxis while 37 received G-CSF only for secondary prophylaxis. Same-day pegfilgrastim compared to next-day pegfilgrastim or filgrastim was the most common G-CSF dosing utilized with primary and secondary prophylaxis patients receiving it (87.5%, 94.6%) respectively. As shown in Table, primary and secondary prophylaxis groups were similar on baseline characteristics (p>0.05); the primary outcome of FN (p>0.05); all secondary outcomes (p>0.05) except for a higher frequency of dose delays in secondary (37.8%) vs primary prophylaxis patients (14.6%; p=0.01); and mean absolute neutrophil counts (ANC) in all cycles (p>0.05) except for cycles 3 and 5. Higher ANC levels were found in primary prophylaxis patients (4.06+0.43) vs secondary prophylaxis (3.03+0.30; p=0.03) for cycle 3 and (3.57+0.25) vs (2.88+0.26; p=0.03) for cycle 5. Conclusion: In this single-center retrospective study, BR-treated lymphoma and CLL patients receiving primary vs secondary with G-CSF showed similar outcomes except, notably, for chemotherapy dose delays that may put secondary patients at risk for poor treatment outcomes. Further research is needed to evaluate the impact of primary vs secondary prophylaxis on chemotherapy treatment outcomes. Table Disclosures Persky: Sandoz: Consultancy; Debiopharm: Other: Member, Independent Data Monitoring Committee; Bayer: Consultancy; Morphosys: Other: Member, Independent Data Monitoring Committee. McBride:Sanofi Genzyme: Consultancy; Sandoz: Consultancy; teva: Consultancy.


1999 ◽  
Vol 17 (11) ◽  
pp. 3676-3681 ◽  
Author(s):  
Charles L. Bennett ◽  
Jane A. Weeks ◽  
Mark R. Somerfield ◽  
Joe Feinglass ◽  
Thomas J. Smith

PURPOSE: The American Society of Clinical Oncology (ASCO) Health Services Research Committee sought to assess whether more appropriate patterns of colony-stimulating factor (CSF) use occurred after the publication of ASCO evidence-based practice guidelines in 1994 and 1996 for patients with solid tumors or lymphoma. METHODS: In 1994 and 1997, questionnaires describing clinical scenarios were mailed to ASCO members who practiced medical oncology. Physicians were asked the extent to which they preferred to use a CSF for primary prophylaxis, secondary prophylaxis, or treatment of neutropenic complications. Multiple regression analyses were used to determine predictors of overall propensity to use CSFs and, when using a CSF, propensity to support longer schedules of CSF use. RESULTS: Decreased use of CSFs was shown in the following situations: (1) treatment for febrile neutropenia without localizing signs (39% in 1994 v 29% in 1997) or with a right lower lobe infiltrate (54% v 46%); (2) primary prophylaxis with paclitaxel for ovarian cancer (20% v 11%) or cyclophosphamide, doxorubicin, and vincristine chemotherapy for small-cell lung cancer (8.4% v 4.6%); and (3) secondary prophylaxis after afebrile neutropenia following chemotherapy for germ cell tumors (44.5% v 36.0%). One third fewer physicians supported the extended use of CSFs until an absolute neutrophil count ≥ 10,000/mm3 or a WBC count ≥ 10,000/mm3 was reached, both counts serving as criteria for stopping CSF therapy. However, we observed high rates of CSF use despite ASCO guideline recommendations against use in the following clinical situations: (1) primary prophylaxis in patients at low risk of febrile neutropenia (6% v 16%); (2) secondary prophylaxis late in the course of curative and palliative therapy (80% v 53%); and (3) treatment of afebrile and uncomplicated febrile neutropenia (30% v 60%). In 1994 and 1997, fee-for-service physicians were more likely than other physicians to prefer use of CSF support while maintaining treatment dose and schedule instead of using dose-reduction strategies, and, when using a CSF, they were more likely to support longer CSF treatment schedules (P < .05 for both scenarios). CONCLUSION: Decreased use and more appropriate use of CSFs in accordance with ASCO guideline recommendations occurred from 1994 to 1997, but there remain many opportunities to reduce CSF use with no clinical harm. Many oncologists continue to support the use of CSFs in scenarios and with scheduling criteria that the guidelines and evidence do not support. ASCO's evidence-based guidelines should be linked with formal continuous quality improvement initiatives to substantially improve the quality of supportive oncology care.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 144-144
Author(s):  
Andrés Jesús Muñoz Martin ◽  
Pilar Garcia Alfonso ◽  
Luis Gonzalez Bayon ◽  
Wenceslao Vasquez Jimenez ◽  
Ana Belen Ruperez Blanco ◽  
...  

144 Background: Neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) is a new treatment modality in gastric cancer with peritoneal seeding. Several phase I-II clinical trials with NIPS and cytoreductive surgery have shown an increase in overall survival in Japanese patients (pts) with acceptable toxicity. We report the toxicity related to neutropenia and granulocyte colony stimulating factor (G-CSF) use of the first experience in Spain with NIPS (DCF-like) in gastric cancer with peritoneal carcinomatosis. Methods: Ten consecutive pts have been enrolled in this protocol in a compassionate use program in our center from 2009 to 2011. Chemotherapy (DCF-like) was delivered through an implantable peritoneal catheter. Primary prophylaxis with GCS-F was not used as described in the phase II studies, except in one pt. Clinical characteristics (Table). Results: The incidence of grade 3–4 neutropenia was 70% and any grade neutropenia 80%. Febrile neutropenia was described in 50% of the pts. All pts received secondary prophylaxis according to ASCO guidelines. No treatment-related deaths were observed. One pt discontinued chemotherapy due to febrile neutropenia and diarrhoea. There were no complications due to the infection of peritoneal catheter. Late or unexpected toxicities have not been observed. Conclusions: The first results suggest febrile neutropenia rate of this treatment modality exceeds the 20% ASCO threshold. Primary prophylaxis with G-CSF should be considered in this setting. [Table: see text]


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6107-6107 ◽  
Author(s):  
D. C. Dale ◽  
L. E. Cosler ◽  
D. A. Wolff ◽  
E. Culakova ◽  
M. S. Poniewierski ◽  
...  

6107 Background: Although recent economic analyses of prophylactic G-CSF provide cost saving febrile neutropenia (FN) risk estimates of approximately 20%, many regimens have reported rates <20%. A prospective nationwide cohort study was undertaken to develop risk models for neutropenic complications (NC) including severe and febrile neutropenia in patients receiving cancer chemotherapy (Lyman ASCO 2005). A cost-effectiveness model is presented to evaluate the economic impact of G-CSF prophylaxis based on the model. Methods: Data on 974 consecutive breast cancer patients receiving adjuvant chemotherapy at 115 randomly selected practice sites were analyzed. The clinical and cost impact of G-CSF prophylaxis in high-risk patients based on the model was compared with: 1) no G-CSF; 2) primary prophylaxis; and 3) secondary prophylaxis. Pegfilgrastim costs were based on Medicare pricing while hospitalization costs and mortality on national hospitalization data. Results: Independent predictors of first cycle NC included: type and schedule of chemotherapy, diabetes, elevated bilirubin, planned RDI >85%, low glomerular filtration rate and low neutrophil count. Prophylactic G-CSF was associated with a decreased risk. Model R2=0.327 and c-statistic=0.80 [95% CI: 0.78–0.83; P<.001]. At a baseline FN risk of 8.4% per cycle, the expected costs over four cycles of chemotherapy were: no pegfilgrastim: $1,285; primary prophylaxis: $2,573; secondary prophylaxis: $2,040 and model-targeted G-CSF: $1,527. Expected cost varied with FN risk and model performance. Primary prophylaxis was associated with lower cost than no prophylaxis at FN risk >18%, while the model outperformed both strategies at an FN risk >10%. At a baseline cycle risk of FN of 8.4%, model-guided G-CSF was associated with an expected cost of $44,980 per life saved. Cost savings increased as model discrimination increased. The model was consistently associated with lower cost compared to secondary prophylaxis. Conclusions: A risk model for NC has been developed in breast cancer patients receiving adjuvant chemotherapy. Use of the model to guide G-CSF support appears to be cost-effective at an overall FN risk of 10%. [Table: see text]


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19401-e19401
Author(s):  
Edward C. Li ◽  
Dylan Mezzio ◽  
Andrew Spargo ◽  
Kimberley J. Campbell ◽  
Gary H. Lyman

e19401 Background: Patients with nonmetastatic NSCLC receiving platinum-based chemotherapy are at an intermediate risk (10-20%) of developing FN; clinical practice guidelines recommend assessing whether these patients have FN risk factors before considering myeloid growth factor (MGF) prophylaxis. Most NSCLC patients receiving chemotherapy have ≥1 FN risk factors, and while PP leads to lower rates of FN across all cycles, it is more costly compared to SP. This study evaluates the cost-effectiveness of PP vs. SP using a biosimilar MGF, filgrastim-sndz, in NSCLC patients at intermediate risk of FN. Methods: A Markov model with a lifetime horizon was constructed to evaluate the total costs and clinical outcomes of using filgrastim-sndz as PP vs. SP in NSCLC patients 61 years old receiving adjuvant carboplatin/paclitaxel every 3 weeks for 4 cycles. Separate analyses were conducted for patients with 0 FN risk factors (0RF) and with ≥1 FN risk factors (1+RF), representing 11.3% and 18% baseline FN risk, respectively. Incremental cost-effectiveness ratios (ICERs) were calculated for cost per FN event avoided, life-year saved (LYS), and quality-adjusted life-year (QALY) gained from a United States payer perspective. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. Results: For patients with 0RF, use of filgrastim-sndz as PP vs. SP provided an additional 0.056 QALYs (0.079 LYS) at an incremental cost of $3,266. The ICERs were $46,815, $41,555, and $58,531 for cost per FN event avoided, cost per LYS, and cost per QALY gained, respectively. For patients with 1+RF, PP vs. SP added 0.090 QALYs (0.127 LYS) at an incremental cost of $1,605. The ICERs were $13,970, $12,644, and $17,805 for cost per FN event avoided, cost per LYS, and cost per QALY gained, respectively. In the PSA, the likelihood of cost-effectiveness at a willingness-to-pay (WTP) threshold of $50,000 per QALY gained was 31.7% for patients with 0RF and 96.6% for 1+RF. Conclusions: For NSCLC patients at intermediate risk of FN receiving adjuvant carboplatin/paclitaxel with 1+RF, PP with filgrastim-sndz compared to SP is cost-effective based on a WTP threshold of $50,000/QALY. [Table: see text]


2021 ◽  
pp. bmjspcare-2021-003082
Author(s):  
Florian Scotte ◽  
Hélène Simon ◽  
Philippe Laplaige ◽  
Eric-Charles Antoine ◽  
Caroline Spasojevic ◽  
...  

ObjectivesFebrile neutropenia (FN) commonly occurs during cancer chemotherapy. Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) is known to reduce the severity and incidence of FN and infections in patients with cancer. Despite the proven efficacy, G-CSFs are not always prescribed as recommended. We performed a discrete-choice experiment (DCE) to determine what factors drive the physician preference for FN prophylaxis in patients with cancer undergoing chemotherapy.MethodsAttributes for the DCE were selected based on literature search and on expert focus group discussions and comprised pain at the injection site, presence of bone pain, associated fever/influenza syndrome, efficacy of prophylaxis, biosimilar availability, number of injections per chemotherapy cycle and cost. Oncologists, in a national database, were solicited to participate in an online DCE. The study collected the responses to the choice scenarios, the oncologist characteristics and their usual prescriptions of G-CSFs in the context of breast, lungs and gastrointestinal cancers.ResultsOverall, the responses from 205 physicians were analysed. The physicians were mainly male (61%), with ≤20 years of experience (76%) and working only in public hospitals (73%). The physicians prescribe G-CSF primary prophylaxis for 32% of patients: filgrastim in 46% and pegfilgrastim in 54%. The choice of G-CSF for primary and secondary prophylaxis was driven by cost and number of injections. Biosimilars were well accepted.ConclusionCost and convenience of G-CSF drive the physician decision to prescribe or not G-CSF for primary and secondary FN prophylaxes. It is important that these results be incorporated in the optimisation of G-CSF prescription in the clinical setting.


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