Intravenous and subcutaneous formulations of trastuzumab, and trastuzumab biosimilars: implications for clinical practice.
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SUBMITTER: Waller CF
PROVIDER: S-EPMC8039027 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundBiologic treatments impose a large financial burden on healthcare payers. Subcutaneous formulations of trastuzumab and rituximab offer administration cost savings relative to the intravenous products through reduced preparation and infusion times. However, intravenous biosimilars have the potential to offset administration costs through lower drug costs.ObjectiveThe objective was to develop a budget impact model (BIM) from a payer's perspective for the EU-5 countries (UK, France, Germany, Spain, Italy) to demonstrate the economic impact of using intravenous trastuzumab and rituximab biosimilars.MethodsAn incidence-based BIM was developed to estimate the net budget impact utilising epidemiology data from the literature, market research data on the use of relevant treatments in all approved indications, and corresponding costs. The budget impact was estimated for 5 years following introduction of the biosimilars.ResultsAnalysis using the base-case results indicated that adoption of the biosimilars trastuzumab and rituximab would result in net cost savings. At year 5, the net budget saving ranged from €4.05 million to 303.86 million for rituximab and from €19 million to 172 million for trastuzumab. The cost saving could potentially extend treatment to 291-15,671 more patients with rituximab and 622-3688 more patients with trastuzumab.ConclusionThis budget impact analysis emphasised that increased use of intravenous rituximab and trastuzumab biosimilars may result in cost savings from the payer's perspective across the EU-5 countries.
| S-EPMC7803676 | biostudies-literature
Project description:BACKGROUND:Trastuzumab is a monoclonal antibody for patients with HER2 (human epidermal growth factor receptor 2)-positive breast cancer, which is added to regular treatment and reduces mortality. Originally, trastuzumab had to be administered intravenously (IV) over 30 min every 3 weeks for 1 year. Since 2012, a formulation for the subcutaneous (SC) administration of trastuzumab has been available, which has not yet been approved in the USA. Advocates claim that the SC formulation saves time and money, despite higher costs. The purpose of this study is to review existing literature concerning the comparative efficacy and risk of harms of trastuzumab IV and SC concerning patient-relevant health outcomes. METHODS:We conducted searches in the Cochrane Library and MEDLINE for articles published through May 2018 in English or German. In addition, we searched ClinicalTrials.gov to identify unpublished studies. We dually reviewed the abstracts and full-text articles based on a priori defined inclusion criteria, rated the risk of bias of included studies, and assessed the strength of the evidence for each outcome of interest. Because data was insufficient for quantitative synthesis, we summarized results narratively. RESULTS:We identified three RCTs (randomized controlled trials) meeting our eligibility criteria, which included data on 1003 patients. We found moderate evidence for similar event rates (20.05% vs. 18%, HR (hazard ratio) 0.88, CI 95% = 0.62-1.27), and mortality rates (10% vs. 8%, HR 0.76, CI 95% = 0.44-1.32) after 1.7 years for patients receiving trastuzumab IV and for patients receiving SC. Results remained similar after 3.3 years, though evidence lacked strength due to a high dropout rate. All trials reported more adverse events among the SC group than in the IV group. Evidence for these findings was of moderate strength. Nevertheless, more than 85% of the patients preferred trastuzumab SC over IV. Results concerning serious adverse events appeared to be heterogeneous. CONCLUSION:Results of studies indicate similar efficacy between the two routes of administration. The higher rates of adverse events for SC administration were mainly attributable to injection site-related events. The clinical decision of whether to administer trastuzumab SC or IV requires the consideration of several factors and should be determined individually.
| S-EPMC6905114 | biostudies-literature
Project description:The monoclonal antibody trastuzumab (Herceptin®), which targets the human epidermal growth factor receptor 2 (HER2), is approved for the treatment of early breast and advanced breast and gastric cancer in which HER2 is overexpressed. Several biosimilar versions of trastuzumab are expected to enter the European market over the course of 2018 and 2019. The biosimilar development pathway consists of a comprehensive comparability exercise between the biosimilar candidate and the reference product, primarily focussing on data from analytical studies. Clinical studies for biosimilar candidates follow a different design to those for a new biological, as the aim is not to independently establish clinical benefit, but to confirm biosimilarity between the two agents. The different trastuzumab biosimilar candidates have followed diverse pathways in their clinical development, with differences in clinical trial design (equivalence or non-inferiority design), patient population (those with metastatic or early breast cancer) and endpoint (overall response rate or pathological complete response). These differences in approach in phase 3 testing must be viewed in the totality of evidence demonstrating biosimilarity. Adequate information on the biosimilar approval pathway, the nature of the biosimilarity exercise and how the clinical development of a biosimilar is tailored to meet the licensing requirements can help informed decision making in clinical practice.
| S-EPMC6738325 | biostudies-literature
Project description:ImportanceConfirmation of long-term comparability between subcutaneous and intravenous trastuzumab is essential.ObjectiveTo evaluate efficacy and safety of subcutaneous trastuzumab compared with that of intravenous trastuzumab for patients with ERBB2 (HER2)-positive early breast cancer after 6 years' follow-up in the HannaH (Enhanced Treatment With Neoadjuvant Herceptin) trial.Design, setting, and participantsOpen-label, prospective, multicenter, international, neoadjuvant-adjuvant, randomized, phase 3 noninferiority clinical trial (primary end points: pathologic complete response and serum trough concentration predose cycle 8) conducted for 596 patients with ERBB2-positive early breast cancer enrolled from October 19, 2009, to December 1, 2010.InterventionsEligible patients received 8 cycles of chemotherapy (4 cycles of docetaxel, 75 mg/m2, followed by 4 cycles of fluorouracil, 500 mg/m2, epirubicin, 75 mg/m2, and cyclophosphamide, 500 mg/m2) with either fixed-dose subcutaneous trastuzumab, 600 mg, or intravenous trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) every 3 weeks in the neoadjuvant setting. Patients received an additional 10 cycles of subcutaneous trastuzumab or intravenous trastuzumab (according to their initial randomization) after surgery in the adjuvant setting to complete 1 year of anti-ERBB2 therapy.Main outcomes and measuresEvent-free and overall survival rates were calculated using the Kaplan-Meier method. Hazard ratios were estimated by Cox proportional hazards regression. Adverse events and serious adverse events were graded per standard criteria.ResultsIn total, 294 women (mean [SD] age, 50.3 [11.1] years) treated with subcutaneous trastuzumab and 297 women (mean [SD] age, 49.5 [10.8] years) treated with intravenous trastuzumab were included in respective intention-to-treat populations. Six-year event-free survival rates (65% in both study groups; hazard ratio, 0.98; 95% CI, 0.74-1.29) and overall survival rates (84% in both study groups; hazard ratio, 0.94; 95% CI, 0.61-1.45) were similar between the subcutaneous and intravenous trastuzumab groups. Patients achieving a total pathologic complete response had longer event-free survival and higher 6-year overall survival rates than those with residual disease. Incidence of adverse events (290 of 297 [97.6%] vs 282 of 298 [94.6%]), grade 3 or higher adverse events (158 of 297 [53.2%] vs 160 of 298 [53.7%]), cardiac events (44 of 297 [14.8%] vs 42 of 298 [14.1%]), and serious adverse events (65 of 297 [21.9%] vs 45 of 298 [15.1%]) was comparable between the subcutaneous and intravenous trastuzumab treatment groups.Conclusions and relevanceThis final analysis of the HannaH trial further confirms the comparable efficacy and safety of subcutaneous and intravenous trastuzumab and highlights the suitability of subcutaneous trastuzumab as an alternative route of administration for patients with ERBB2-positive early breast cancer.Trial registrationClinicalTrials.gov identifier: NCT00950300.
| S-EPMC6512301 | biostudies-literature
Project description:Human epidermal growth factor receptor 2 (HER2) positive breast cancer is an entity with aggressive behaviour. One year of adjuvant trastuzumab significantly improves the disease free survival in the range of 40-50% and reduces the risk of dying from HER2 positive breast cancer by one third. Adjuvant treatment with trastuzumab became available in Slovenia in 2005 and the aim of this study is to explore, if the exceptional results reported in adjuvant clinical trials are achieved also in daily clinical practice.An analysis of tumour and patient characteristics, type of treatment and outcome (relapse free and overall survival) of 313 patients (median age 52 years) treated at the Institute of Oncology Ljubljana in years 2005-2009 was performed.Median follow-up was 4.4 years. Sixty-one patients relapsed and 24 died. Three and four years relapse free survival was 84.2% and 80.8% and the overall survival was 94.4% and 92.5%, respectively. Independent prognostic factors for relapse were tumour grade (HR 2.10; 95% CI 1.07-4.14; p = 0.031) and nodal stage (HR 1.35; 1.16-1.56; p < 0.0001) and for the overall survival nodal stage only (HR 1.36; 1.05-1.78; p = 0.021).The outcome in patients with adjuvant trastuzumab in daily clinical practice, treated by medical oncologists, is comparable to results obtained in international adjuvant studies.
| S-EPMC4230562 | biostudies-other
Project description:Early and effective glycemic control can prevent or delay the complications associated with type 2 diabetes (T2D). The benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming increasingly recognized and they now feature prominently in international T2D treatment recommendations and guidelines across the disease continuum. However, despite providing effective glycemic control, weight loss, and a low risk of hypoglycemia, GLP-1RAs are currently underutilized in clinical practice. The long-acting GLP-1RA, semaglutide, is available for once-weekly injection and in a new once-daily oral formulation. Semaglutide is an advantageous choice for the treatment of T2D since it has greater efficacy in reducing glycated hemoglobin and body weight compared with other GLP-1RAs, has demonstrated benefits in reducing major adverse cardiovascular events, and has a favorable profile in special populations (e.g., patients with hepatic impairment or renal impairment). The oral formulation represents a useful option to help improve acceptance and adherence compared with injectable formulations for patients with a preference for oral therapy, and may lead to earlier and broader use of GLP-1RAs in the T2D treatment trajectory. Oral semaglutide should be taken on an empty stomach, which may influence the choice of formulation. As with most GLP-1RAs, initial dose escalation of semaglutide is required for both formulations to mitigate gastrointestinal adverse events. There are also specific dose instructions to follow with oral semaglutide to ensure sufficient gastric absorption. The evidence base surrounding the clinical use of semaglutide is being further expanded with trials investigating effects on diabetic retinopathy, cardiovascular outcomes, and on the common T2D comorbidities of obesity, chronic kidney disease, and non-alcoholic steatohepatitis. These will provide further information about whether the benefits of semaglutide extend to these other indications.
| S-EPMC8276717 | biostudies-literature
Project description:BackgroundSubcutaneous (SC) versus intravenous (IV) administration is advantageous in terms of patient convenience and hospital efficiency. This study aimed to compare the effect of optimizing the processes involved in SC versus IV administration of rituximab and trastuzumab on hospital capacity and service quality.MethodsThis cross-sectional resource utilization study interviewed oncologists, hematologists, nurses, and pharmacists from 10 hospitals in Spain to estimate changes in processes associated with conversion from IV to SC rituximab and trastuzumab, based on clinical experience and healthcare use from administrative databases.ResultsEfficient use of SC formulations increased the monthly capacity for parenteral administration by 3.35% (potentially increasable by 5.75% with maximum possible conversion according to the product label). The weekly capacity for hospital pharmacy treatment preparation increased by 7.13% due to conversion to SC formulation and by 9.33% due to transferring SC preparation to the cancer treatment unit (potentially increasable by 12.16 and 14.10%, respectively). Monthly hospital time decreased by 33% with trastuzumab and 47% with rituximab. In a hypothetical hospital, in which all processes for efficient use of SC rituximab and/or trastuzumab were implemented and all eligible patients received SC formulations, the estimated monthly capacity for preparation and administration increased by 23.1% and estimated hospital times were reduced by 60-66%.ConclusionsConversion of trastuzumab and rituximab to SC administration could improve the efficiency of hospitals and optimize internal resource management processes, potentially increasing care capacity and improving the quality of care by reducing time spent by patients at hospitals.
| S-EPMC8034176 | biostudies-literature
Project description:BACKGROUND:Despite the benefits biosimilars offer in terms of cost savings and patient access, healthcare professionals and patients have been reluctant to use them. Next to insufficient understanding of and trust in biosimilars, healthcare professionals and patients have questions about switching and the nocebo effect when using biosimilars in clinical practice. In addition, clear motivation to use biosimilars may be lacking among these stakeholders. OBJECTIVE:This study aims to provide recommendations on how to improve biosimilar use on both a clinical and a practical level based on insights from healthcare professionals (physicians, hospital pharmacists, nurses), patients (or their representatives), and regulators across Europe. METHODS:We conducted 44 semi-structured interviews with experts from five stakeholder groups across Europe: physicians, hospital pharmacists, nurses, regulators, and patients/representatives. Interviews were transcribed ad verbatim and transcripts analysed according to the thematic framework method. RESULTS:Based on the insights and considerations of the experts interviewed, we identified a number of recommendations to improve the use of biosimilars in clinical practice. Regarding switch implementation, the experts voiced support for the following actions: (1) disseminate evidence from and experience with (multiple) switching; (2) provide clear, one-voice regulatory guidance about the interchangeability of biosimilars and their reference product; (3) apply a multi-stakeholder implementation and communication protocol to guide switching in clinical practice; (4) apply a pragmatic approach when taking switch decisions; and (5) avoid mandated switching, allowing stakeholder communication and alignment. When discussing approaches to increase the willingness of stakeholders to use biosimilars, we concluded that actions should be centred on (1) communicating the benefits provided by biosimilars and the introduction of market competition, (2) increasing awareness among stakeholders about medicine prices and their societal responsibility to use medicines in a cost-effective manner, (3) transparent reporting about the allocation of savings, (4) sharing biosimilar usage data among hospitals and prescribers to allow peer-to-peer benchmarking, and (5) applying a balanced combination of tangible and non-tangible incentives that can be tailored to offset the time and effort expended by stakeholders when switching to a biosimilar. CONCLUSIONS:This study proposes a number of strategic, practical, and overarching recommendations to support healthcare professionals and inform decision makers to improve the clinical use of biosimilars and the willingness of stakeholders to use them. The proposed solutions to fully realise the potential of biosimilars for healthcare systems and patients include developing practical switch guidance, being transparent about the gains from biosimilar use (and how savings are allocated), and developing a combination of non-tangible and tangible incentives for involved stakeholders.
| S-EPMC7669768 | biostudies-literature
Project description:Within PrefHer (NCT01401166), patients and healthcare professionals (HCPs) preferred subcutaneous (SC) over intravenous (IV) trastuzumab. We undertook a prospective, observational time and motion study to quantify patients' time in infusion chairs and active HCP time in PrefHer. Patients with HER2-positive early breast cancer received four adjuvant cycles of SC trastuzumab (600 mg fixed dose via SC single-use injection device [SID, Cohort 1] or SC handheld syringe [HHS, Cohort 2]) then four cycles of standard IV trastuzumab or the reverse sequence. Generic case report forms for IV and SC management, both in the treatment room and the drug preparation area, were tailored to reflect center practices. Patient chair time and active HCP time were recorded. We compared pooled Cohort 1 + 2 IV with Cohort 1 SC SID and Cohort 2 SC HHS mean times across eight countries and individually within them utilizing a random intercept generalized linear mixed-effects model. Per session, the SC SID saved a mean of 57 min of patient chair time versus IV (range across countries: 47-86; P < 0.0001); the SC HHS saved 55 min (40-81; P < 0.0001). Active HCP time was reduced by a mean of 13 min per session with the SC SID (range across countries: 4-16; P < 0.0001) and 17 min with the SC HHS (5-28; P < 0.0001) versus IV. SC trastuzumab, delivered via SID or HHS, saved patient chair and active HCP times versus IV infusion, supporting a transition to either SC method.
| S-EPMC4799946 | biostudies-literature
Project description:PURPOSE:Trastuzumab (TZM) improves survival and the risk of recurrence among patients with early-stage HER2+ breast cancer (BC). TZM treatment can be given intravenously (IV-TZM) or subcutaneously (SC-TZM). Although both methods have similar efficacy and safety, they differ in dosage and administration. Previous studies of cost minimization determined that SC-TZM is associated with lower costs than IV-TZM; however, those studies did not include the costs associated with body weight-based dosage and the treatment of adverse drug reactions (ADRs). METHODS/PATIENTS:We performed a model-based cost-minimization analysis. The analysis included direct and indirect medical costs associated with TZM preparation (adjusted by body weight) and administration and also costs due to severe ADRs and non-medical costs that occurred during the total treatment course (18 cycles). We performed a sensitivity analysis to test the robustness of the results across various TZM costs and patient body weights. RESULTS:The overall cost (in USD) of IV-TZM treatment was $83,309.1 per patient compared with $77,067.7 per patient for SC-TZM. Thus, one year of SC-TZM treatment cost $6,241.4 less per patient than one year of IV-TZM treatment. The sensitivity analysis revealed that the results were mainly driven by the price of each TZM vial and body weight. CONCLUSION:SC-TZM is a cost-saving therapy for Chilean patients with early-stage HER2+ BC. Given their similar efficacy and safety, we suggest the use of SC formulations rather than IV formulations. The use of SC-TZM instead of IV-TZM may have a significant economic impact on public/private healthcare systems.
| S-EPMC7001963 | biostudies-literature