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. Issue 7 (11th December 2013)

• Record Type: Journal Article
• Authors: Stadler, Walter M.; Vaughn, David J.; Sonpavde, Guru; Vogelzang, Nicholas J.; Tagawa, Scott T.; Petrylak, Daniel P.; Rosen, Peter; Lin, Chia‐Chi; Mahoney, John; Modi, Sanjiv; Lee, Peter; Ernstoff, Marc S.; Su, Wu‐Chou; Spira, Alexander; Pilz, Korinna; Vinisko, Richard; Schloss, Charles; Fritsch, Holger; Zhao, Charles; Carducci, Michael A.
• Is Part Of: Cancer. Volume 120:Issue 7(2014)
• Page Start: 976
• Page End: 982
• Publication Date: 2013-12-11
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28519
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr28519-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>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.</p> </sec> <sec id="cncr28519-sec-0002" sec-type="section"> <title>METHODS</title> <p>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.</p> </sec> <sec id="cncr28519-sec-0003" sec-type="section"> <title>RESULTS</title> <p>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.</p> </sec> <sec id="cncr28519-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>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. <bold><italic>Cancer</italic> 2014;120:976–982</bold>. © <italic>2013 American Cancer Society</italic>.</p> </sec> </abstract>