Safety and efficacy of eltrombopag (epag) versus placebo (pbo) for the treatment (tx) of chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumors receiving gemcitabine (gem)-based chemotherapy (ctx): A phase I study

Background: There are limited tx options for CIT. Epag, an oral, small molecule, thrombopoietin-receptor agonist that increases platelet (plt) production, is being explored for tx of CIT. Methods: This was the Ph I portion of a Ph I/II, blinded, pbo-controlled multicenter study in adults with solid tumors and baseline plts 300,000μL, who received up to 6 cycles of gem (1000-1250 mg/m2 IV) as monotherapy on Days 1, 8, and 15 Q28 days or Days 1 and 8 Q21 days in combination with cisplatin (50-80 mg/m2 IV Day 1 or divided 1 and 8) or carboplatin (AUC 4-7 IV Day 1). Patients received ctx alone for Cycle 1 and ctx plus epag or matching pbo (randomized 3:1) daily on Days -5 to -1 and 2 to 6 for subsequent cycles. Epag or pbo was interrupted for plts 400,000/μL. Results: 33 patients were randomized; 26 received epag or pbo (Table). Data review with an external, independent physician found no safety concerns, and there were sufficient plt increases with a dose of 100 mg epag vs pbo. No dose-limiting toxicities were reported for epag but 1 for pbo. Most AEs were grade 1 or 2. The most common AE in combined epag- and combined pbo-treated groups was neutropenia. Conclusions: Epag was well-tolerated and improved plt counts. Based on these encouraging Ph I results, Ph II using 100 mg epag in thrombocytopenic patients is planned. (Table Presented).