One year versus a shorter duration of adjuvant trastuzumab for HER2-positive early breast cancer: a systematic review and meta-analysis

522 Background: One year of adjuvant trastuzumab (T) remains the standard treatment for patients with HER2 positive breast cancer. Results from randomized trials with diverse non-inferiority margins comparing one year to a shorter duration of adjuvant T were not consistent, particularly with the PERSEPHONE and the final PHARE and Short-HER trials’ results. Our objective was to conduct a systematic review and meta-analysis of randomized trials in patients with HER2 positive breast cancer to assess whether a shorter duration of adjuvant T was non-inferior to one year of treatment. Methods: PubMed, EMBASE and The Cochrane Library were searched for eligible randomized trials. Hazard ratios (HR) for disease free and overall survival (DFS, OS) were weighted using generic inverse variance and pooled in a meta-analysis using random-effects models. The median of non-inferiority margins derived from each trial was calculated to set a non-inferiority margin of 1.29 for the pooled analysis. Subgroup analyses compared survival outcomes by estrogen receptor (ER) status, nodal status, length and timing of trastuzumab treatment. Results: Data of 11,376 patients from 5 trials were analyzed. A shorter duration of T was non-inferior to one year of therapy for DFS (HR 1.13, 95%CI 1.03-1.24) but worse for OS (HR 1.16, 95%CI 1.01-1.32). In addition, the non-inferiority for DFS was met for patients with ER positive disease (HR 1.1, 95%CI 0.95-1.28) and patients treated with 6 months (HR 1.09, 95%CI 0.98-1.22) or sequential T (HR 0.97, 95%CI 0.75-1.27). Conversely, the non-inferiority for DFS was not met for patients with ER negative disease (HR 1.22, 95%CI 1.06-1.41), patients treated with 9 weeks (HR 1.26, 95%CI 1.02-1.55) or concomitant T (HR 1.25, 95%CI 1.07-1.45) and patients with node negative (HR 1.12, 95% 0.93-1.35) or positive (HR 1.16, 95%CI 0.99-1.36) disease. Conclusions: Within the limitations of the available data and the different non-inferiority margins used in randomized trials, a shorter duration of adjuvant T is non-inferior to one year of therapy for DFS in patients with HER2 positive breast cancer, particularly in patients with ER positive disease. Further trials with appropriately chosen non-inferiority margins are needed to confirm the optimal duration of T in patients with low-risk disease.

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Adjuvant trastuzumab regimen for HER2-positive early-stage breast cancer: a systematic review and meta-analysis

Expert Review of Clinical Pharmacology ◽

10.1080/17512433.2019.1637252 ◽

2019 ◽

Vol 12 (8) ◽

pp. 815-824 ◽

Cited By ~ 4

Author(s):

Anne Julienne Genuino ◽

Usa Chaikledkaew ◽

Due Ong The ◽

Thanyanan Reungwetwattana ◽

Ammarin Thakkinstian

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Early Stage ◽

Meta Analysis ◽

Early Stage Breast Cancer ◽

Her2 Positive ◽

Adjuvant Trastuzumab

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Real-World Setting Cost-Effectiveness Analysis Comparing Three Therapeutic Schemes of One-Year Adjuvant Trastuzumab in HER2-Positive Early Breast Cancer from the Cyprus NHS Payer Perspective

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17124339 ◽

2020 ◽

Vol 17 (12) ◽

pp. 4339

Author(s):

Savvas S. Ioannou ◽

Yiola Marcou ◽

Eleni Kakouri ◽

Michael A. Talias

Keyword(s):

Breast Cancer ◽

Cost Effectiveness ◽

Early Breast Cancer ◽

Real World ◽

Cost Effective ◽

Her2 Positive ◽

Adjuvant Trastuzumab ◽

Lifetime Horizon ◽

Effectiveness Analysis ◽

One Year

Introduction: This study is one of the first real-world cost-effectiveness analyses of one-year adjuvant trastuzumab used in HER2-positive early female breast cancer in comparison to chemotherapy alone. It is just the second one in Europe, the first one in Cyprus, and the fourth one worldwide ever carried out using real-world data. Methods: Using a Markov model (four health states), a cost-effectiveness analysis was carried out both over 20 years and for a lifetime horizon. The sampling method used in this study was the randomized sampling of 900 women. Results: The findings for the 20-year horizon showed that all trastuzumab arms were more cost-effective, with a willingness-to-pay threshold of only €60,000 per quality-adjusted life year (QALY) [incremental cost-effectiveness ratios (ICER): €40,436.10/QALY]. For the lifetime horizon, with thresholds of €20,000, €40,000, and €60,000/QALY, all trastuzumab arms were found to be more cost-effective (ICER: €17,753.85/QALY). Moreover, for the 20-year and the lifetime horizons, with thresholds of €20,000/QALY, €40,000/QALY, and €60,000/QALY, the most cost-effective of the three subgroups (anthracyclines and then trastuzumab, no anthracyclines and then trastuzumab, and anthracyclines, taxanes, and trastuzumab) was that of anthracyclines and then trastuzumab (ICER: €18,301.55/QALY and €8954.97/QALY, respectively). Conclusions: The study revealed that adjuvant trastuzumab for one year in female HER2-positive early breast cancer can be considered cost-effective.

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Herceptin® (trastuzumab) in HER2-positive early breast cancer: a systematic review and cumulative network meta-analysis

Systematic Reviews ◽

10.1186/s13643-018-0854-y ◽

2018 ◽

Vol 7 (1) ◽

Cited By ~ 12

Author(s):

Florence R. Wilson ◽

Megan E. Coombes ◽

Christine Brezden-Masley ◽

Mariya Yurchenko ◽

Quinlan Wylie ◽

...

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Early Breast Cancer ◽

Meta Analysis ◽

Her2 Positive

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Abstract P6-17-16: Efficacy and safety of shorter duration of adjuvant trastuzumab for patients with HER2 positive early breast cancer: A meta-analysis of randomized controlled trials

10.1158/1538-7445.sabcs18-p6-17-16 ◽

2019 ◽

Author(s):

J Li ◽

G Wang ◽

Q Wu ◽

C Chen ◽

Y Tu ◽

...

Keyword(s):

Breast Cancer ◽

Randomized Controlled Trials ◽

Early Breast Cancer ◽

Meta Analysis ◽

Controlled Trials ◽

Efficacy And Safety ◽

Her2 Positive ◽

Adjuvant Trastuzumab ◽

Randomized Controlled

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Herceptin® (trastuzumab) in HER2-positive early breast cancer: protocol for a systematic review and cumulative network meta-analysis

Systematic Reviews ◽

10.1186/s13643-017-0588-2 ◽

2017 ◽

Vol 6 (1) ◽

Cited By ~ 7

Author(s):

Florence R. Wilson ◽

Megan E. Coombes ◽

Quinlan Wylie ◽

Mariya Yurchenko ◽

Christine Brezden-Masley ◽

...

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Early Breast Cancer ◽

Meta Analysis ◽

Her2 Positive

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LBA11 Individual patient data meta-analysis of 5 non-inferiority RCTs of reduced duration single agent adjuvant trastuzumab in the treatment of HER2 positive early breast cancer

Annals of Oncology ◽

10.1016/j.annonc.2021.08.2083 ◽

2021 ◽

Vol 32 ◽

pp. S1283

Author(s):

H.M. Earl ◽

L. Hiller ◽

J.A. Dunn ◽

P.F. Conte ◽

R. D'Amico ◽

...

Keyword(s):

Breast Cancer ◽

Early Breast Cancer ◽

Individual Patient Data ◽

Meta Analysis ◽

Single Agent ◽

Patient Data ◽

Her2 Positive ◽

Adjuvant Trastuzumab

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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 ◽

10.1136/bmjopen-2019-035802 ◽

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.

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