Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma

Objective To determine the efficacy of the thrombopoietin receptor agonist romiplostim for the prevention of temozolomide-induced thrombocytopenia in newly diagnosed glioblastoma. Methods In the PLATUM phase II open-label, multicenter, single-arm trial, patients diagnosed with Common Terminology Criteria for Adverse Events grade 3 or 4 thrombocytopenia during chemoradiotherapy received weekly subcutaneous romiplostim injections. PLATUM aimed at demonstrating that the percentage of thrombocytopenic patients treated with romiplostim able to complete 6 cycles of maintenance temozolomide chemotherapy exceeded 10% (p0 = 0.10; pA = 0.35). Using type I error equal to 0.05% and 95% power, 31 patients had to be recruited. According to a Fleming 2-step design with a preplanned interim analysis after recruitment of 20 patients (step 1), the trial was terminated early for success. Results Twenty patients were enrolled in step 1. Median age was 61 years (range 33–73). Twelve patients received 6 temozolomide cycles, corresponding to a success rate of 60% (95% confidence interval 36%–81%). Four patients discontinued temozolomide because they did not respond to romiplostim, 2 for progression, and 2 for adverse events unrelated to romiplostim. Conclusion The thrombopoietin receptor agonist romiplostim improves exposure to chemotherapy in patients with glioblastoma experiencing temozolomide-induced thrombocytopenia. Clinicaltrials.gov identifier NCT02227576. Classification of evidence This study provides Class IV evidence that for patients with glioblastoma and thrombocytopenia, romiplostim is effective for the secondary prophylaxis of temozolomide-induced thrombocytopenia.