An open-label, single-arm, phase 2 trial of the Polo-like kinase inhibitor volasertib (BI 6727) in patients with locally advanced or metastatic urothelial cancer.

Abstract

BACKGROUND:

Polo-like kinases (Plks) control multiple steps during the cell cycle, and Plk1 is overexpressed in urothelial cancer (UC). Volasertib (BI 6727), a Plk inhibitor, has demonstrated antitumor activity in several malignancies, including UC. In this phase 2 trial, the authors investigated volasertib as a second-line treatment in advanced/metastatic UC.

METHODS:

Patients who progressed within 2 years of 1 prior chemotherapy regimen received 300 mg volasertib on day 1 every 3 weeks. The dose was escalated to 350 mg in cycle 2 if volasertib was tolerated in cycle 1. The primary endpoint was tumor response, which was assessed every 6 weeks; secondary endpoints were progression-free survival, overall survival, duration of response, safety, and pharmacokinetics.

RESULTS:

Fifty patients were enrolled, and the median patient age was 68.5 years (range, 52-83 years). All patients had received prior platinum, 94% of patients had relapsed ≤2 years after prior therapy, 36% had liver metastases, and 54% had lung metastases. The median number of treatment cycles was 2 (range, 1-27 treatment cycles), and 23 patients were dose escalated at cycle 2. Seven patients (14%) had a partial response, 13 (26%) had stable disease, and 30 (60%) progressed within 6 weeks. The median response duration was 41 weeks (range, 29.1-77.3 weeks). The median progression-free survival was 1.4 months, and the median overall survival was 8.5 months. The most frequent grade 3 and 4 adverse events were neutropenia (28%), thrombocytopenia (20%), and anemia (16%). No cumulative toxicity was observed.

CONCLUSIONS:

Volasertib as second-line treatment for advanced/metastatic UC had an acceptable safety profile but demonstrated insufficient antitumor activity for further evaluation as a monotherapy.

• Authors: Walter M Stadler, David J Vaughn, Guru Sonpavde, Nicholas J Vogelzang, Scott T Tagawa, Daniel P Petrylak, Peter Rosen, Chia-Chi Lin, John Mahoney, Sanjiv Modi, Peter Lee, Marc S Ernstoff, Wu-Chou Su, Alexander Spira, Korinna Pilz, Richard Vinisko, Charles Schloss, Holger Fritsch, Charles Zhao, Michael A Carducci
• Journal: Cancer (Cancer) Vol. 120 Issue 7 Pg. 976-82 (Apr 01 2014) ISSN: 1097-0142 [Electronic] United States
• PMID: 24339028 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 American Cancer Society.

Chemical References

• Antineoplastic Agents
• BI 6727
• Protein Kinase Inhibitors
• Pteridines
• Protein Serine-Threonine Kinases

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents (pharmacokinetics, therapeutic use)
• Disease-Free Survival
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis
• Protein Kinase Inhibitors (pharmacokinetics, therapeutic use)
• Protein Serine-Threonine Kinases (antagonists & inhibitors)
• Pteridines (pharmacokinetics, therapeutic use)
• Treatment Outcome
• Urologic Neoplasms (drug therapy, enzymology, metabolism, pathology)