A phase I study of volasertib combined with afatinib, in advanced solid tumors
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To determine the maximum tolerated dose (MTD) of volasertib, a Polo-like kinase inhibitor, combined with afatinib, an oral irreversible ErbB family blocker, in patients with advanced solid tumors (NCT01206816; Study 1230.20).
Patients with advanced non-resectable and/or metastatic disease following failure of conventional treatment received intravenous volasertib 150–300 mg on day 1 every 21 days, combined with oral afatinib 30–40 mg on days 2–21 of a 3-week cycle (Schedule A), or 50–90 mg on days 2–6 of a 3-week cycle (Schedule B). The primary objective was to determine the MTD of volasertib in combination with afatinib.
Fifty-seven patients (Schedule A, N = 29; Schedule B, N = 28) were treated. The MTDs were volasertib 300 mg plus afatinib 30 mg days 2–21 and 70 mg days 2–6 of a 3-week cycle for Schedules A and B, respectively. The most common Grade 3/4 adverse events were neutropenia (31.0 %), diarrhea (13.8 %), and thrombocytopenia (10.3 %) in Schedule A; neutropenia (39.3 %), thrombocytopenia (35.7 %), hypokalemia (14.3 %), febrile neutropenia, and nausea (each 10.7 %) in Schedule B. The best overall response was two partial responses (6.9 %; both in Schedule A); eight patients in each schedule achieved stable disease. Volasertib showed multi-exponential pharmacokinetic (PK) behavior; co-administration of volasertib and afatinib had no significant effects on the PK profile of either drug.
Volasertib combined with afatinib had manageable adverse effects and limited antitumor activity in this heavily pretreated population.
KeywordsAdvanced cancer Volasertib Afatinib PLK EGFR Phase I trial
Medical writing assistance, financially supported by Boehringer Ingelheim, was provided by Victoria A. Robb of GeoMed, an Ashfield business, part of UDG Healthcare plc, during the preparation of this manuscript. We would like to thank Valerie Kets and Els De Backer (SCS Boehringer Ingelheim Comm.V, Clinical Operations, Brussels, Belgium) for their monitoring support. We also thank the study coordinators at the participating study centers: Anne Moxhon (Université Catholique de Louvain, Brussels, Belgium), Annie De Gussem and Stefanie Viktor (Ghent University, Ghent, Belgium), and Joke Dycke, Rika Lamens and Peggy De Clercq (Antwerp University Hospital, Edegem, Belgium).
This work was supported by Boehringer Ingelheim.
Compliance with ethical standards
Conflict of interest
Jean-Pascal Machiels has been an advisor for Boehringer Ingelheim but without financial compensation. Marina De Smet, Natalja Strelkowa, and Dan Liu are employees of Boehringer Ingelheim. Korinna Pilz was an employee of Boehringer Ingelheim at the time of execution and analysis of the study. All remaining authors have declared no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. This article does not contain any studies with animals performed by any of the authors.
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