scholarly journals Economic evaluation of adjuvant trastuzumab emtansine in patients with HER2-positive early breast cancer and residual invasive disease after neoadjuvant taxane and trastuzumab–based treatment in Canada

2020 ◽  
Vol 27 (6) ◽  
Author(s):  
T. Younis ◽  
A. Lee ◽  
M.E. Coombes ◽  
N. Bouganim ◽  
D. Becker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Incremental Cost ◽  
Systemic Treatment ◽  
Invasive Disease ◽  
Cost Utility ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Health States ◽  
Adjuvant Trastuzumab

Background In the katherine trial, adjuvant trastuzumab emtansine [T-DM1, Kadcyla (Genentech, South San Francisco, CA, U.S.A.)], compared with trastuzumab, significantly reduced the risk of recurrence or death by 50% (unstratified hazard ratio: 0.50; 95% confidence interval: 0.39 to 0.64; p < 0.0001) in patients with her2-positive early breast cancer (ebc) and residual invasive disease after neoadjuvant systemic treatment. A cost–utility evaluation, with probabilistic analyses, was conducted to examine the incremental cost per quality-adjusted life–year (qaly) gained associated with T-DM1 relative to trastuzumab, given the higher per-cycle cost of T-DM1. Methods A Markov model comprising a number of health states was used to examine clinical and economic out­comes over a lifetime horizon from the Canadian public payer perspective. Patients entered the model in the invasive disease-free survival (idfs) state, where they received either T-DM1 or trastuzumab. Transition probabilities between the health states were derived from the katherine trial, Canadian life tables, and published literature from other relevant clinical trials (emilia, cleopatra, and M77001). Resource use, costs, and utilities were derived from katherine, other clinical trials, published literature, provincial fee schedules, and clinical expert opinion. Sensitivity analyses were conducted for key assumptions and model parameters. Results Compared with trastuzumab, adjuvant T-DM1 was associated with a cost savings of $8,300 per patient and a 2.16 incremental qaly gain; thus T-DM1 dominated trastuzumab. Scenario analyses yielded similar results, with T-DM1 dominating trastuzumab or producing highly favourable incremental cost–utility ratios of less than $10,000 per qaly. Conclusions Adjuvant T-DM1 monotherapy is a cost-effective strategy compared with trastuzumab alone in the treatment of patients with her2-positive ebc and residual invasive disease after neoadjuvant systemic treatment.

Projected long-term impact of adjuvant trastuzumab emtansine (T-DM1) on metastatic breast cancer occurrence in Turkey.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12523-e12523
Author(s):  
David J. Press ◽  
Gözde Özcan ◽  
Ezgi Teksoy ◽  
Akanksha Tomar ◽  
Cedric Revil ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Population Level ◽  
Invasive Disease ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Disease Free

e12523 Background: Progression from early stage breast cancer (eBC) to metastatic breast cancer (mBC) constitutes a substantial disease burden in Turkey. At a population-level, investment in treatment with curative intent may contribute to long-term reductions or delays in mBC. Women diagnosed with human epidermal growth factor receptor 2 (HER2)-positive eBC who do not achieve pathologic complete response (pCR) after neoadjuvant taxane and trastuzumab-based treatment may be indicated for adjuvant trastuzumab emtansine (T-DM1) monotherapy. For this clinical population, the KATHERINE trial (NCT01772472) demonstrated significantly higher invasive disease-free survival among women who received adjuvant T-DM1 relative to trastuzumab (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; p<0.001). Methods: We developed epidemiology models based on data from cancer registries, observational studies, clinical trials, estimated population-level T-DM1 uptake, and extrapolations, by calendar year to predict the population-level number of women who will avoid mBC in Turkey over the next 10 years (i.e., 2022 to 2031). Weighted transitional probability averages were based on invasive disease-free and overall survival curves from the KATHERINE trial. Results: Over the next 10 years in Turkey, we projected that 22,597 women will be diagnosed with HER2-positive eBC and will not achieve pCR after neoadjuvant therapy. We projected that the total number of women who will experience mBC occurrence following adjuvant T-DM1 use from 2022-2031 will decrease annually from 0 to 249 relative to projections without introduction of T-DM1, with a cumulative total of 1,219 women not experiencing mBC occurrence, corresponding to 17% of total projected mBC occurrence over the next decade. At year 10 (2031), we projected that 29% fewer women would experience mBC occurrence in Turkey (604 with TDM-1 vs. 853 with trastuzumab). Conclusions: Population-level improvements in HER2-positive eBC to mBC disease progression are expected over the next 10 years in Turkey following adjuvant T-DM1 monotherapy. Further research will elucidate treatment-related improvements in costs to society as a result of population-level improvements in disease outcomes for women diagnosed with eBC.[Table: see text]

scholarly journals Mechanisms contributing to ado-trastuzumab emtansine (T-DM1)-induced toxicities: a gateway to better understanding ADC-associated toxicities

2021 ◽  
Author(s):  
Yukinori Endo ◽  
Nishant Mohan ◽  
Milos Dokmanovic ◽  
Wen Jin Wu
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Metastatic Breast ◽  
Invasive Disease ◽  
Dependent Manner ◽  
Trastuzumab Emtansine ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Humanized Monoclonal Antibody ◽  
Significant Efficacy

Abstract In order to improve the safety of novel therapeutic drugs, better understanding of the mechanisms of action is important. Ado-trastuzumab emtansine (also known as T-DM1) is an antibody-drug conjugate (ADC) consisting of a humanized monoclonal antibody directed against HER2 (trastuzumab) and a maytansinoid-derived toxin (DM1), which are linked by a non-cleavable thioether linker. T-DM1 has been approved for the treatment of trastuzumab-resistant HER2-positive metastatic breast cancer and recently for use as an adjuvant treatment option for patients with HER2-positive early breast cancer who have residual invasive disease. While the treatment with T-DM1 results in significant efficacy in the selected patient population, nonetheless, there are also concerns with the side effects such as thrombocytopenia and hepatotoxicity. While current understanding of the mechanism of T-DM1-mediated side effects is still incomplete, there have been several reports of HER2-dependent and/or -independent mechanisms that could be associated with the T-DM1-induced adverse events. The results from our laboratory show that T-DM1 binds to cytoskeleton-associated protein 5 (CKAP5) on the cell surface of hepatocytes via its payload component (DM1). This interaction is independent of HER2 and leads to cell growth inhibition and apoptosis of hepatocytes in a T-DM1 dose dependent manner. This review highlights the importance of HER2-independent mechanism of T-DM1 to induce hepatotoxicity, which offers a new insight into a role for CKAP5 in the overall maytansinoid-based ADC (DM1 and DM4)-mediated cytotoxicity. This discovery provides a molecular basis for T-DM1-induced off-target toxicity and opens a new avenue for developing the next generation of ADCs.

Trastuzumab emtansine: a game changer in HER2-positive early breast cancer

2020 ◽  
Vol 16 (32) ◽  
pp. 2595-2609
Author(s):  
Max S Mano
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Pathological Complete Response ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Epidermal Growth ◽  
Game Changer

Trastuzumab emtansine (T-DM1), given postoperatively for 14 cycles to patients with human epidermal growth factor receptor 2-positive (HER2-positive) early breast cancer (EBC) who failed to achieve a pathological complete response after standard chemotherapy and HER2 blockade, represents probably the greatest progress in the management of this aggressive form of breast cancer since the adjuvant trastuzumab pivotal trials. This article addresses the rationale behind the conception of the KATHERINE trial, T-DM1’s structure and pharmacokinetics data, clinical efficacy data of the KATHERINE trial and of other EBC trials with T-DM1, safety aspects, implications of the KATHERINE trial results to clinical practice and future perspectives in the management of HER2-positive EBC.

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