Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma: The PLATUM trial.

Abstract

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.

CLINICALTRIALSGOV 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.

• Authors: Emilie Le Rhun, Patrick Devos, Caroline Houillier, Stéphanie Cartalat, Olivier Chinot, Anna Luisa Di Stefano, Clément Lepage, Nicolas Reyns, François Dubois, Michael Weller
• Journal: Neurology (Neurology) Vol. 93 Issue 19 Pg. e1799-e1806 (11 05 2019) ISSN: 1526-632X [Electronic] United States
• PMID: 31586022 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 American Academy of Neurology.

Chemical References

• Antineoplastic Agents, Alkylating
• Receptors, Fc
• Receptors, Thrombopoietin
• Recombinant Fusion Proteins
• Thrombopoietin
• romiplostim
• Temozolomide

Topics

• Adult
• Aged
• Antineoplastic Agents, Alkylating (adverse effects)
• Brain Neoplasms (therapy)
• Chemoradiotherapy
• Female
• Glioblastoma (therapy)
• Humans
• Male
• Middle Aged
• Receptors, Fc (therapeutic use)
• Receptors, Thrombopoietin (agonists)
• Recombinant Fusion Proteins (therapeutic use)
• Temozolomide (adverse effects)
• Thrombocytopenia (chemically induced, drug therapy, prevention & control)
• Thrombopoietin (therapeutic use)