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.

Cost Effectiveness of Adjuvant Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

2007 ◽  
Vol 25 (6) ◽  
pp. 625-633 ◽  
Author(s):  
Nicola Lucio Liberato ◽  
Monia Marchetti ◽  
Giovanni Barosi
Keyword(s):  
Breast Cancer ◽  
Cost Effectiveness ◽  
Early Breast Cancer ◽  
Growth Factor Receptor ◽  
Local Relapse ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Life Years ◽  
Epidermal Growth ◽  
The Cost

Purpose To evaluate the cost-effectiveness of 12-month adjuvant trastuzumab therapy in women with high-risk human epidermal growth factor receptor 2 (HER2) –positive early breast cancer. Methods A Markov model tracked quarterly patients’ transitions between five health states: disease free, local relapse, disease free after local relapse, metastatic disease, and death. Patients were allowed to incur symptomatic or asymptomatic transient cardiac dysfunction during trastuzumab administration. Probabilities were derived mainly from the combined report of the National Surgical Adjuvant Breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 trials (95% node positive) and a meta-analysis by the Early Breast Cancer Trialists’ Collaborative Group. Costs were estimated from the perspective of the Italian and US health care systems. The analysis was run during a 15-year time horizon. A 3% yearly discount rate was applied to both costs and life-years. Second-order Monte-Carlo and probabilistic sensitivity analyses were performed. Results Adjuvant trastuzumab increases life expectancy by 1.54 (1.18 discounted) quality-adjusted life-years (QALYs). At a cost of €675 and $767 per weekly dose in the Italian and US setting, respectively, trastuzumab achieves its clinical benefit at a cost of €14,861 (95% CI, €3,917 to €44,028) and $18,970 (95% CI, $6,014 to $45,621) per QALY saved. The incremental cost effectiveness was higher than €50,000/QALY (or $60,000/QALY) at time horizons shorter than 7.8 years and for patients older than 76 years or with a 10-year risk of relapse lower than 15%. The results confirmed the cost effectiveness when simulating a Herceptin Adjuvant Trial (HERA) -like scenario at multiway sensitivity analysis. Conclusion In a long-term horizon, adjuvant trastuzumab is a cost-effective therapy for patients with HER2-positive, high-risk, early breast cancer.

scholarly journals Anthracycline-containing versus carboplatin-containing neoadjuvant chemotherapy in combination with trastuzumab for HER2-positive breast cancer: the neoCARH phase II randomized clinical trial

2021 ◽  
Vol 13 ◽  
pp. 175883592110090
Author(s):  
Hong-Fei Gao ◽  
Zhiyong Wu ◽  
Ying Lin ◽  
Xiang-Yang Song ◽  
Yin Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Primary Endpoint ◽  
Growth Factor Receptor ◽  
Group Versus ◽  
Complete Response ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Epidermal Growth ◽  
Positive Breast Cancer

Background: Although dual blockade HER2-based neoadjuvant chemotherapy is associated with excellent outcomes for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, pertuzumab is not available to all patients due to cost. The optimal neoadjuvant chemotherapy for HER2-positive breast cancer in the presence of a single HER2 blockade is unknown. This study aimed to compare the efficacy and safety of epirubicin/cyclophosphamide followed by docetaxel/trastuzumab (EC-TH) with docetaxel/carboplatin/trastuzumab (TCH) neoadjuvant setting for HER2-positive breast cancer under the single HER2 blockade. Methods: Patients with stage II-IIIC HER2-positive breast cancer were randomly assigned to either eight cycles of EC-TH every 3 weeks during all chemotherapy cycles, or six cycles of TCH every 3 weeks. The primary endpoint was pathological complete response (pCR) (defined as the absence of invasive tumor cells in breast and axilla, ypT0/is ypN0). Results: From May 2017 to November 2019, 140 patients were randomly assigned, and 135 patients were ultimately found evaluable for the primary endpoint. The pCR was recorded in 25 of 67 patients [37.3%; 95% confidence interval (CI), 25.8–50.0] in the EC-TH group and in 38 of 68 patients (55.9%, 95% CI, 43.3–67.9) in the TCH group ( p = 0.032). The most common adverse events (AEs) were neutropenia in 24 of 67 (35.8%) patients in the EC-TH group versus 27 of 68 (39.7%) in the TCH group ( p = 0.642), anemia in 33 of 67 (49.3%) patients in the EC-TH group versus 34 of 68 (50.0%) in the TCH group ( p = 0.931), and thrombocytopenia in five of 67 (7.5%) patients in the EC-TH group versus 17 of 68 (25.0%) in the TCH group ( p = 0.006). Conclusion: For patients receiving the single HER2 blockade trastuzumab for HER2-positive breast cancer, TCH regimen might be a preferred neoadjuvant therapy. Trial registration: This trial was registered with ClinicalTrials.gov identifier: NCT03140553) on 2 May 2017.

scholarly journals Optimum duration of adjuvant trastuzumab in treatment of human epidermal growth factor receptor-2 positive early breast cancer: protocol for a network meta-analysis of randomised controlled trials

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e035802
Author(s):  
Qiancheng Hu ◽  
Xin Wang ◽  
Ye Chen ◽  
Xiaofen Li ◽  
Ting Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Early Breast Cancer ◽  
Meta Analysis ◽  
Growth Factor Receptor ◽  
Her2 Positive ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

IntroductionControversy regarding optimum duration of trastuzumab treatment remains in patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer. The objective of applying network meta-analysis (NMA) is to integrate existing evidence based on direct and indirect comparisons of efficacy and safety, and then to determine the duration of trastuzumab treatments with the greatest impact on therapeutic outcomes in HER2-positive early breast cancers.Methods and analysisElectronic searching of trastuzumab treatments for early breast cancer by titles and abstracts will be conducted for the period from inception to 16 June 2019 in PubMed, Cochrane Library, Embase and ClinicalTrils.gov, as well as the annual meetings of San Antonio Breast Cancer Symposium (SABCS), European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) online archives. The outcomes of interest are overall survival, disease-free survival, acceptability, cardiotoxicities and grade 3 to 4 non-haematological toxicities. Two independent reviewers will screen and extract eligible data based on the inclusion and exclusion criteria, and then assess the risk of bias and evidence quality of individual studies using Cochrane Collaboration’s tool and Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The heterogeneity, transitivity and inconsistency of NMA will be evaluated. In addition, we will perform subgroup and sensitivity analyses to assess the robustness and reliability of findings in our NMA.Ethics and disseminationEthics approval is not required for our NMA. Findings from our NMA will be submitted as peer-reviewed journal manuscripts and international conference reports.Trial registration numberCRD42019139109.

scholarly journals Pertuzumab and Trastuzumab Emtansine for Human Epidermal Growth Factor Receptor-2–Positive Metastatic Breast Cancer: Contemporary Population-Based Outcomes

2019 ◽  
Vol 13 ◽  
pp. 117822341987942 ◽  
Author(s):  
Sasha Lupichuk ◽  
Winson Y Cheung ◽  
Douglas Stewart
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Population Based ◽  
Exposed Group ◽  
Trastuzumab Emtansine ◽  
Adjuvant Trastuzumab ◽  
Naive Group ◽  
Epidermal Growth

Background: Real-world outcomes for patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) treated with pertuzumab in combination with taxane chemotherapy plus trastuzumab (TaxTP) in the first line setting and trastuzumab emtansine (TE) in any line of treatment are lacking. Methods: Cohorts of patients treated with (1) TaxTP and (2) TE from January 1, 2013 through December 31, 2016 were retrospectively obtained from a population-based database. Cohorts were described according to age, hormone receptor (HR) status, prior systemic therapies, event-free survival (EFS) defined as time from start of treatment to start of next line of treatment or death, and overall survival (OS). Results: A total of 122 patients were treated with TaxTP and 104 with TE. In the TaxTP cohort, EFS was significantly longer in the trastuzumab-naïve group compared with the adjuvant trastuzumab group (median EFS = 27.0 vs 12.4 months; P = .002). In the TaxTP cohort, median OS was not reached. In the TE cohort, EFS was significantly longer in the pertuzumab-naïve group compared with pertuzumab-exposed group (median time to treatment failure [TTF] = 18.7 vs 5.5 months; P < .001). Overall survival was also significantly longer in the pertuzumab-naïve group compared with the pertuzumab-exposed group (median OS = 23.2 vs 14.1 months; P = .022). In multivariable analyses, adjuvant trastuzumab and prior pertuzumab exposure in the metastatic setting remained significant predictors of inferior EFS for patients treated with TaxTP and TE, respectively. Conclusions: New anti-HER2 therapies appear to be clinically relevant in the real-world.

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