Predicting Thrombocytopenia in Patients With Breast Cancer Treated With Ado-trastuzumab Emtansine

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Abstract

Introduction: Thrombocytopenia is a common and potentially serious adverse event of ado-trastuzumab emtansine (T-DM1) use in patients with advanced breast cancer. However, the risk factors have been minimally explored. Our aim was to develop a clinical prediction model from the clinicopathologic data that would allow for quantification of the personalized risks of thrombocytopenia from T-DM1 usage. Materials and Methods: Data from 3 clinical trials, EMILIA (a study of trastuzumab emtansine versus capecitabine + lapatinib in participants with HER2 [human epidermal growth factor receptor 2]-positive locally advanced or metastatic breast cancer), TH3RESA (a study of trastuzumab emtansine in comparison with treatment of physician's choice in participants with HER2-positive breast cancer who have received at least two prior regimens of HER2-directed therapy), and MARIANNE [a study of trastuzumab emtansine (T-DM1) plus pertuzumab/pertuzumab placebo versus trastuzumab (Herceptin) plus a taxane in participants with metastatic breast cancer], were pooled. Cox proportional hazard analysis was used to assess the association between the pretreatment clinicopathologic data and grade ≥ 3 thrombocytopenia occurring within the first 365 days of T-DM1 use. A multivariable clinical prediction model was developed using a backward elimination process. Results: Of the 1620 participants, 141 (9%) had experienced grade ≥ 3 thrombocytopenia. On univariable analysis, the body mass index, race, presence of brain metastasis, platelet count, white blood cell count, and concomitant corticosteroid use were significantly associated with the occurrence of grade ≥ 3 thrombocytopenia (P < .05). The multivariable prediction model was optimally defined by race (Asian vs. non-Asian) and platelet count (100-220 vs. 220-300 vs. >300 × 10 9/L). A large discrimination between the prognostic subgroups was observed. The highest risk subgroup (Asian and platelet count of 100-220 cells ×10 9/L) had a 40% probability of grade ≥ 3 thrombocytopenia within the first 365 days of T-DM1 therapy compared with 2% for the lowest risk subgroup (non-Asian and platelet count > 300 × 10 9/L). Conclusion: A clinical prediction model, defined by race and pretreatment platelet count, was able to discriminate subgroups with a significantly different risk of grade ≥ 3 thrombocytopenia after T-DM1 initiation. The model allows for improved interpretation of the personalized risks and risk/benefit ratio of T-DM1.

Original languageEnglish
Pages (from-to)e220-e228
JournalClinical Breast Cancer
Volume20
Issue number2
DOIs
Publication statusPublished - Apr 2020

Keywords

  • Advanced breast cancer
  • Adverse event
  • Clinical prediction model
  • Personalized risk
  • T-DM1

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