Effect Of Trastuzumab Emtansine (T-Dm1) On Autologous Platelet Kinetics.

e12521Background: T-DM1 treatment results in Grade 3-4 thrombocytopenia in 8%-13% (1.4% with clinically significant bleeding). Prior in vitro studies reported T-DM1 inhibition of megakaryocyte maturation as the cause of decreased platelet production. The current study was initiated to evaluate the cause of thrombocytopenia in patients. Methods: Patients with HER2-positive metastatic breast cancer (N = 10) were enrolled in this Phase 1 study. 111In radiolabeled autologous platelet recoveries and survivals as well as serial platelet counts, bleeding time assays, platelet aggregation responses to epinephrine, adenosine diphosphate, collagen, arachidonic acid, ristocetin, and thromboxane were performed at baseline and during two consecutive cycles (C) of the drug (3.6mg/kg IV q3weeks). Results: Platelet nadir occurred on days (D) 7, 8, or 9 post-T-DM1 in C1 and at D5-6 in C2. Average nadir counts (% baseline) in C1 and C2 were 116,000/µl (52 ±22%) and 117,000/µl (48 ±31%), respectively, with return to baselin...