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01-10-2015 | Original Article

A phase I study of volasertib combined with afatinib, in advanced solid tumors

Authors: Jean-Pascal Machiels, Marc Peeters, Catherine Herremans, Veerle Surmont, Pol Specenier, Marina De Smet, Korinna Pilz, Natalja Strelkowa, Dan Liu, Sylvie Rottey

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2015

Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusions

Volasertib combined with afatinib had manageable adverse effects and limited antitumor activity in this heavily pretreated population.

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Title: A phase I study of volasertib combined with afatinib, in advanced solid tumors
Authors: Jean-Pascal Machiels
Marc Peeters
Catherine Herremans
Veerle Surmont
Pol Specenier
Marina De Smet
Korinna Pilz
Natalja Strelkowa
Dan Liu
Sylvie Rottey
Publication date: 01-10-2015
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2860-2

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