title: 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: Section of Hematology/Oncology, University of Chicago, Chicago, Illinois.
authors: Walter M
authors: WM
authors: Stadler
authors: David J
authors: DJ
authors: Vaughn
authors: Guru
authors: G
authors: Sonpavde
authors: Nicholas J
authors: NJ
authors: Vogelzang
authors: Scott T
authors: ST
authors: Tagawa
authors: Daniel P
authors: DP
authors: Petrylak
authors: Peter
authors: P
authors: Rosen
authors: Chia-Chi
authors: CC
authors: Lin
authors: John
authors: J
authors: Mahoney
authors: Sanjiv
authors: S
authors: Modi
authors: Peter
authors: P
authors: Lee
authors: Marc S
authors: MS
authors: Ernstoff
authors: Wu-Chou
authors: WC
authors: Su
authors: Alexander
authors: A
authors: Spira
authors: Korinna
authors: K
authors: Pilz
authors: Richard
authors: R
authors: Vinisko
authors: Charles
authors: C
authors: Schloss
authors: Holger
authors: H
authors: Fritsch
authors: Charles
authors: C
authors: Zhao
authors: Michael A
authors: MA
authors: Carducci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011621:Pteridines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; C541363:BI 6727; D047428:Protein Kinase Inhibitors; D011621:Pteridines; D017346:Protein Serine-Threonine Kinases
keywords: phase 2 trial; polo-like kinase inhibitor; urothelial cancer; volasertib