Clinical outcome of single agent volasertib (BI 6727) as second-line treatment of patients (pts) with advanced or metastatic urothelial cancer (UC).

Abstract

4567 Background: No standard therapy exists for metastatic UC pre-treated with a platinum-based regimen. Polo-like kinase 1 (Plk1) controls multiple essential steps of mitosis and is therefore an interesting target for anticancer therapy. Volasertib is a cell cycle kinase inhibitor that targets Plk1 and has shown preliminary antitumor activity in different malignancies, including a partial response in a pretreated UC pt. We report preliminary efficacy and safety data of a phase II trial of volasertib as second-line therapy for metastatic UC. Methods: Pts with metastatic UC who progressed after 1 prior chemotherapy or relapsed within 2 years of (neo)adjuvant chemotherapy received 300 mg volasertib (2-hour iv infusion) on day 1 every 3 weeks (w). If well tolerated, dose escalation to 350 mg in cycle 2 was encouraged. Primary endpoint was objective tumor response (RECIST) assessed every 6 w; secondary endpoints were PFS, OS, duration of response, safety and PK. An early stopping rule required ≥10% objective response rate in the first 20 pts. Results: Recruitment has completed. Since December 2009, 50 pts were enrolled and treated; 9 pts are still on treatment as of January 19, 2011. All pts are evaluable for safety and efficacy analyses. Pt characteristics were: median age 69 years (52-83), ECOG PS (%): 0 (50), 1 (46), 2 (4); 40% of pts had >2 metastatic sites; 29% of pts relapsed >6 months after prior therapy. Median number of cycles was 2 (range: 1-19), 22 pts had dose escalation to 350 mg. Preliminary best response data are: 7 pts (14%) had partial response, 12 pts (24%) had stable disease and 31 (62 %) progressed within 6 weeks after study entry. To date, median duration of response is 25 w (12-53 w) and median PFS is 6 w. Drug-related grade 3 or 4 adverse events (AEs) were neutropenia (24%), thrombocytopenia (16%), anemia (10%). Nonhematologic AEs were mild and uncommon, and no cumulative toxicity was observed. Overall survival data are pending. Conclusions: Single agent volasertib as second-line treatment of advanced/metastatic UC was well tolerated and showed antitumor activity. Further assessment of volasertib in combination with other active compounds in metastatic UC is warranted.