Dataset Information

Subcutaneous injection of trastuzumab into the thigh versus abdominal wall in patients with HER2-positive early breast cancer: Pharmacokinetic, safety and patients' preference - Substudy of the randomised phase III GAIN-2 study.

ABSTRACT:

Background

Trastuzumab given intravenously in combination with chemotherapy is standard of care for patients with early HER2-positive breast cancer (BC). Different randomised studies have shown equivalent efficacy of a subcutaneous injection into the thigh compared to the intravenous formulation. Other body regions for injection have not been investigated but might be more convenient for patients.

Methods

After surgery, patients were randomised to receive either subcutaneous trastuzumab into the thigh or into the abdominal wall (AW). Patient preferences were evaluated using validated questionnaires (PINT). Primary objectives of this multicentre, non-blinded, randomised substudy of the GAIN-2 study were to investigate pharmacokinetics of the injection into the thigh versus AW and to determine patients' preferences of either administration site versus the previously received intravenous application.

Results

226 patients were randomised and 219 patients (thigh: N = 110; AW: N = 109) formed the modified intent-to-treat (mITT). Overall, 83.5% (out of N = 182 with information about patients' preference) preferred subcutaneous over previous intravenous application or had no preference. Preference was similar between both administration sites (thigh: 80.6%; AW: 86.5; p = 0.322). Pharmacokinetic analysis included 30 patients. Geometric means of C_max and AUC_0-21d were higher in thigh than in AW group (geometric mean ratio with body weight adjustment: C_max: 1.291, 90%-CI 1.052-1.584; AUC_0-21d: 1.291, 90%-CI 1.026-1.626). Safety profile was in line with previous reports of subcutaneous trastuzumab.

Conclusion

Subcutaneous trastuzumab into the thigh showed an approximately 30% higher bioavailability. Injections were well tolerated and preferred over intravenous administration. The subcutaneous injection into the thigh should remain the standard of care.

SUBMITTER: Reinisch M

PROVIDER: S-EPMC9563210 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Subcutaneous injection of trastuzumab into the thigh versus abdominal wall in patients with HER2-positive early breast cancer: Pharmacokinetic, safety and patients' preference - Substudy of the randomised phase III GAIN-2 study.

Reinisch Mattea M Untch Michael M Mahlberg Rolf R Reimer Toralf T Hitschold Thomas T Marmé Frederik F Aydogdu Mustafa M Schmatloch Sabine S Lück Hans-Joachim HJ Schmidt Marcus M Ladda Ekkehart E Sinn Bruno Valentin BV Klare Peter P Janni Wolfgang W Jackisch Christian C Denkert Carsten C Seiler Sabine S Göhler Thomas T Michel Laura L Burchardi Nicole N Stickeler Elmar E Rey Julia J Klutinus Nicole N Möbus Volker V Loibl Sibylle S

Breast (Edinburgh, Scotland) 20221005

<h4>Background</h4>Trastuzumab given intravenously in combination with chemotherapy is standard of care for patients with early HER2-positive breast cancer (BC). Different randomised studies have shown equivalent efficacy of a subcutaneous injection into the thigh compared to the intravenous formulation. Other body regions for injection have not been investigated but might be more convenient for patients.<h4>Methods</h4>After surgery, patients were randomised to receive either subcutaneous trast ...[more]

PMID: 36223695

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Project description:Background & aimsNo prospective studies have examined the association between thigh subcutaneous fat distribution and non-alcoholic fatty liver disease (NAFLD). We investigated the associations of thigh subcutaneous fat distribution with incidence and remission of NAFLD in a community-based prospective cohort.MethodsWe followed 1,787 subjects, who underwent abdominal ultrasonography, abdominal and femoral magnetic resonance imaging scans, and anthropometric assessments. Associations of thigh subcutaneous fat area/abdominal fat area ratio and thigh circumference/waist circumference ratio with incidence and remission of NAFLD were estimated using the modified Poisson regression model.ResultsOver a mean 3.6-year follow-up, 239 incident cases of NAFLD and 207 regressed cases of NAFLD were identified. Increasing thigh subcutaneous fat area/abdominal fat area ratio was associated with a lower risk of incident NAFLD and a higher likelihood of remission of NAFLD [risk ratio (RR) per SD: 0.69, 95% CI 0.59-0.81; 1.20, 95% CI 1.07-1.34, respectively). Each one SD increase in thigh circumference/waist circumference ratio was associated with a 16% lower risk of incident NAFLD (RR 0.84, 95% CI 0.76-0.94) and a 22% higher likelihood of remission of NAFLD (RR 1.22, 95% CI 1.11-1.34). Additionally, the effects of thigh subcutaneous fat area/abdominal fat area ratio on the incidence and remission of NAFLD were mediated through adiponectin (14.9% and 26.6%), homeostasis model assessment of insulin resistance (9.5% and 23.9%), and triglyceride (7.5% and 19.1%).ConclusionsThese results demonstrated that a favourable fat distribution, characterised by a greater ratio of thigh subcutaneous fat to abdominal fat, had a protective role against NAFLD.Impact and implicationsThe associations of thigh subcutaneous fat distribution with NAFLD incidence and remission have not been prospectively examined in a community-based cohort. Our findings suggest that greater thigh subcutaneous fat relative to a given amount of abdominal fat has a protective effect against NAFLD among the middle-aged and older Chinese populations.

Project description:Purpose: In Peru, breast cancer (BC) stands as the most predominant malignancy neoplasm among women. Trastuzumab has marked a significant milestone in the management of this disease. It has been shown to improve prognosis in human epidermal growth factor receptor 2 (HER2)-expressing female patients, but its repercussions and efficacy are yet to be analyzed in a context with limited resources. Methods: The study population is made of woman patients aged 18 years and older diagnosed with HER2-positive BC at Instituto Nacional de Enfermedades Neoplásicas (INEN, Lima, Peru) during 2019-2021 and treated with at least one dose of subcutaneous trastuzumab. We reviewed medical records to register treatment characteristics, adverse events (AEs), disease progression, and survival status. We considered a median follow-up time of 36 and 45 months for progression and survival status. Results: The majority of patients were over 50 years old (54.29%). Tumor size averaged 19.7 ± 16.1 mm. Lymph nodes were present in 44.78% of patients. Most patients received adjuvant chemotherapy (63.8%) as first-line treatment. Descriptive analyses of treatment outcomes revealed a 30% toxicity rate, primarily attributed to arthralgia (47.62%), followed by diarrhea, fatigue, and injection site reactions, with relatively lower discontinuation rates compared to larger scale studies. Differences in demographic, clinical, and treatment characteristics were not statistically significant concerning the emergence of AEs (p > 0.05). Progression appeared in nine patients, and the overall survival (OS) rate stood at 98.6% and 92.8%, respectively, during a median follow-up of 36 and 45 months. Conclusion: The research suggests that subcutaneous trastuzumab is comparable in effectiveness and safety to the intravenous administration. Regional-specific studies may provide valuable insights into demographic factors influencing treatment outcomes in Peru or other countries. Furthermore, it could represent a more accessible alternative, potentially enhancing patient adherence and optimizing healthcare resource logistics.

Dataset Information

Subcutaneous injection of trastuzumab into the thigh versus abdominal wall in patients with HER2-positive early breast cancer: Pharmacokinetic, safety and patients' preference - Substudy of the randomised phase III GAIN-2 study.

Background

Methods

Results

Conclusion

Publications

Subcutaneous injection of trastuzumab into the thigh versus abdominal wall in patients with HER2-positive early breast cancer: Pharmacokinetic, safety and patients' preference - Substudy of the randomised phase III GAIN-2 study.

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