A randomized, double-blind, placebo-controlled, dose ranging study to assess the efficacy and safety of eltrombopag in patients receiving carboplatin/paclitaxel for advanced solid tumors

Abstract

Objectives:

Eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, has been shown to increase platelet counts in adults with chronic immune thrombocytopenia and chronic hepatitis C. This multicenter phase 2 study assessed the efficacy and safety of eltrombopag in patients receiving first-line carboplatin/paclitaxel for the treatment of advanced solid tumors.

Research design and methods:

Patients (N = 183) were randomized to placebo or eltrombopag 50 mg, 75 mg, or 100 mg given orally following chemotherapy on days 2 through 11 of each 21-day cycle, for at least two cycles. The primary endpoint was the difference in platelet count from day 1 in cycle 2 to the platelet nadir in cycle 2.

Clinical trial registry number:

NCT00102726.

Results:

Although the primary endpoint was not met, postnadir platelet counts increased during cycles 1 and 2 in all eltrombopag treatment groups compared with placebo. The most commonly reported adverse events across all study arms (including placebo) were nausea and alopecia and eltrombopag was generally well tolerated.

Conclusions:

This study provides preliminary information that eltrombopag does increase platelets in patients receiving chemotherapy for advanced solid tumors. Further investigation is needed to identify the optimal dose(s) and schedule of eltrombopag in patients receiving myelosuppressive chemotherapy.

Key words::

• Carboplatin
• Chemotherapy
• Eltrombopag
• Paclitaxel
• Solid tumors
• Thrombocytopenia

Transparency

Declaration of funding

This work was supported by GlaxoSmithKline, Collegeville, PA, USA, and Research Triangle Park, NC, USA.

Declaration of financial/other relationships

R.P., C.M. and Y.M.K. have disclosed that they are employees of, and stockholders in, GlaxoSmithKline. A.K., A.J.-G. and I.N.B. declare that they have no conflicts to disclose.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgement

The authors acknowledge the editorial assistance of Lauren Cerruto and AOI Communications, L.P. in the preparation of this manuscript. Brendan Johnson of GSK provided PK analysis, and Kimberly Marino and Mary Richardson of GSK provided critical review.