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

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Abstract
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.
Keywords
Phase I trial, EGFR, PLK, Afatinib, Advanced cancer, Volasertib, KINASE INHIBITOR, BI 6727, DOSE-ESCALATION, OPEN-LABEL, CANCER-THERAPY, LUNG-CANCER, TRIAL, MALIGNANCIES, RECEPTORS, TARGETS

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Citation

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Chicago
Machiels, Jean-Pascal, Marc Peeters, Catherine Herremans, Veerle Surmont, Pol Specenier, Marina De Smet, Korinna Pilz, Natalja Strelkowa, Dan Liu, and Sylvie Rottey. 2015. “A Phase I Study of Volasertib Combined with Afatinib, in Advanced Solid Tumors.” Cancer Chemotherapy and Pharmacology 76 (4): 843–851.
APA
Machiels, J.-P., Peeters, M., Herremans, C., Surmont, V., Specenier, P., De Smet, M., Pilz, K., et al. (2015). A phase I study of volasertib combined with afatinib, in advanced solid tumors. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 76(4), 843–851.
Vancouver
1.
Machiels J-P, Peeters M, Herremans C, Surmont V, Specenier P, De Smet M, et al. A phase I study of volasertib combined with afatinib, in advanced solid tumors. CANCER CHEMOTHERAPY AND PHARMACOLOGY. 2015;76(4):843–51.
MLA
Machiels, Jean-Pascal, Marc Peeters, Catherine Herremans, et al. “A Phase I Study of Volasertib Combined with Afatinib, in Advanced Solid Tumors.” CANCER CHEMOTHERAPY AND PHARMACOLOGY 76.4 (2015): 843–851. Print.
@article{6965326,
  abstract     = {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.},
  author       = {Machiels, Jean-Pascal and Peeters, Marc and Herremans, Catherine and Surmont, Veerle and Specenier, Pol and De Smet, Marina and Pilz, Korinna and Strelkowa, Natalja and Liu, Dan and Rottey, Sylvie},
  issn         = {0344-5704},
  journal      = {CANCER CHEMOTHERAPY AND PHARMACOLOGY},
  language     = {eng},
  number       = {4},
  pages        = {843--851},
  title        = {A phase I study of volasertib combined with afatinib, in advanced solid tumors},
  url          = {http://dx.doi.org/10.1007/s00280-015-2860-2},
  volume       = {76},
  year         = {2015},
}

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