Do all patients with HER2 positive breast cancer require one year of adjuvant trastuzumab? A systematic review and meta-analysis

Autor: Xiang Y. Ye, Jacques Raphael, Theodore A. Vandenberg, R. Gabriel Boldt, Phillip S. Blanchette, Prakesh S. Shah, Paul Stewart, Ricardo J. Fernandes
Rok vydání: 2020
Předmět:
Oncology
Cancer Research
Time Factors
Receptor
ErbB-2
medicine.medical_treatment
Disease
law.invention
Antineoplastic Agents
Immunological
0302 clinical medicine
Randomized controlled trial
Trastuzumab
law
HER2 Positive Breast Cancer
Medicine
Breast
030212 general & internal medicine
skin and connective tissue diseases
Adjuvant
Randomized Controlled Trials as Topic
Standard treatment
Absolute risk reduction
General Medicine
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Treatment Outcome
Chemotherapy
Adjuvant
030220 oncology & carcinogenesis
Meta-analysis
Original Article
Female
medicine.drug
Adult
medicine.medical_specialty
Breast Neoplasms
Subgroup analysis
Equivalence Trials as Topic
lcsh:RC254-282
Disease-Free Survival
03 medical and health sciences
HER2
Internal medicine
Humans
Aged
business.industry
Surgery
business
030215 immunology
Zdroj: The Breast : Official Journal of the European Society of Mastology
Breast, Vol 54, Iss, Pp 203-210 (2020)
ISSN: 0960-9776
Popis: One year of adjuvant trastuzumab is considered the standard treatment for patients with HER2 positive breast cancer. However, a shorter duration of trastuzumab may be associated with reduced costs and side effects. Results from randomized trials with diverse non-inferiority margins comparing one year to a shorter duration of adjuvant trastuzumab are not consistent and have not been systematically reviewed using a non-inferiority meta-analysis approach. We conducted a systematic review and meta-analysis of randomized trials to assess whether a shorter duration of adjuvant trastuzumab was non-inferior to one year of treatment or not. The non-inferiority margin for the meta-analysis was pre-defined as the median of the margins of all the trials included. Data of 11,376 patients from 5 trials were analyzed. Non-inferiority margins in included studies varied from 1.15 to 1.53 with median of 1.29 for HR of DFS. A shorter duration of trastuzumab was non-inferior to one year of therapy for DFS (HR 1.13, 95%CI 1.03–1.24) but inconclusive for OS (HR 1.14, 95%CI 1.00–1.30). In a subgroup analysis for DFS outcome, shorter therapy was non-inferior in patients with ER positive disease (HR 1.10, 95%CI 0.95–1.28) and those with sequential therapy (HR 0.97, 95%CI 0.75–1.27) and when the duration of treatment was 6 months (HR 1.09, 95%CI 0.98–1.22). Although a shorter duration of adjuvant trastuzumab was non-inferior to one year of therapy for DFS in patients with HER2 positive breast cancer based on our HR margin of 1.29, any benefit of a shorter duration comes at a loss of efficacy with an increase in absolute risk up to 3.9% for 5 year DFS. Whether the potential increased risk is clinically acceptable for the benefits of a shorter duration remains debatable.
Highlights • Shorter duration of adjuvant trastuzumab in HER2 positive breast cancer is attractive. • Inconsistent results seen from the PHARE and PERSEPHONE trials. • Meta-analysis suggests shorter duration of trastuzumab is non-inferior. • Highlights need for appropriately chosen and applied non-inferiority margin.
Databáze: OpenAIRE
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