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Intravenous and subcutaneous formulations of trastuzumab, and trastuzumab biosimilars: implications for clinical practice.

ABSTRACT: Trastuzumab is a biologic therapy indicated for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer and metastatic gastric cancer. Trastuzumab was originally approved as an intravenous (IV) formulation but has since been developed for subcutaneous (SC) administration for patients with HER2-positive breast cancer. Both formulations demonstrate generally comparable pharmacological and clinical profiles. Therefore, when deciding between treatment options, factors such as the route of administration, patient preference, value and cost must be considered. Studies comparing IV with SC trastuzumab indicate that each formulation offers unique advantages to patients depending on their individual needs. Concurrent with the development of SC trastuzumab, IV trastuzumab biosimilars comprise another treatment option that, in view of their reduced cost, might improve patient access and increase cost-effectiveness for healthcare providers and payers. In this review, we seek to raise awareness of the current options available for trastuzumab so that healthcare providers can optimally treat patients according to their individual situations and preferences.

SUBMITTER: Waller CF

PROVIDER: S-EPMC8039027 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Intravenous and subcutaneous formulations of trastuzumab, and trastuzumab biosimilars: implications for clinical practice.

Waller Cornelius F CF Möbius Julia J Fuentes-Alburo Adolfo A

British journal of cancer 20210216 8

Trastuzumab is a biologic therapy indicated for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer and metastatic gastric cancer. Trastuzumab was originally approved as an intravenous (IV) formulation but has since been developed for subcutaneous (SC) administration for patients with HER2-positive breast cancer. Both formulations demonstrate generally comparable pharmacological and clinical profiles. Therefore, when deciding between treatment options, factors ...[more]

PMID: 33589773

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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.

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.

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.

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Intravenous and subcutaneous formulations of trastuzumab, and trastuzumab biosimilars: implications for clinical practice.

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Intravenous and subcutaneous formulations of trastuzumab, and trastuzumab biosimilars: implications for clinical practice.

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