Predicting Thrombocytopenia in Patients With Breast Cancer Treated With Ado-trastuzumab Emtansine
Date
2020
Authors
Modi, N.D.
Sorich, M.J.
Rowland, A.
McKinnon, R.A.
Koczwara, B.
Wiese, M.D.
Hopkins, A.M.
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Clinical Breast Cancer, 2020; 20(2):e220-e228
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<h4>Introduction</h4>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.<h4>Materials and methods</h4>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.<h4>Results</h4>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<sup>9</sup>/L). A large discrimination between the prognostic subgroups was observed. The highest risk subgroup (Asian and platelet count of 100-220 cells ×10<sup>9</sup>/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<sup>9</sup>/L).<h4>Conclusion</h4>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.
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Copyright 2019 Elsevier