A randomised phase II trial of the Polo-like kinase inhibitor BI 2536 in chemo-naïve patients with unresectable exocrine adenocarcinoma of the pancreas – a study within the Central European Society Anticancer Drug Research (CESAR) collaborative network

• Published in: British journal of cancer Vol. 107; no. 2; pp. 280 - 286
• Main Authors: Mross, K, Dittrich, C, Aulitzky, W E, Strumberg, D, Schutte, J, Schmid, R M, Hollerbach, S, Merger, M, Munzert, G, Fleischer, F, Scheulen, M E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.07.2012; Nature Publishing Group
• Subjects: 631/92/436/108; 692/699/67/1059/99; 692/699/67/1504/1713; Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - enzymology; Adenocarcinoma - metabolism; Aged; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell cycle; Cell Cycle Proteins - antagonists & inhibitors; Cell Cycle Proteins - metabolism; Clinical Study; Cohort Studies; Collaboration; Confidence Intervals; Disease-Free Survival; Drug dosages; Drug Resistance; Epidemiology; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Kinases; Leukopenia; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical prognosis; Medical research; Medical sciences; Middle Aged; Molecular Medicine; Neutropenia; Oncology; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - enzymology; Pancreatic Neoplasms - metabolism; Polo-Like Kinase 1; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - metabolism; Pteridines - adverse effects; Pteridines - pharmacokinetics; Pteridines - therapeutic use; Thrombocytopenia; Tumors; Europe; Austria; Germany; BI 2536; phase II; pancreatic cancer; Plk1 inhibitor; Antineoplastic agent; Exocrine pancreas; Research; Cancerology; Pancreas cancer; Phase II trial; Network; Clinical trial; Pancreatic disease; Human; Drug; Digestive system; Enzyme; Transferases; Malignant tumor; Kinase; Unresectable; Digestive diseases; Inhibitor; Pancreas adenocarcinoma; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2012.257

Background: BI 2536, a novel Polo-like kinase 1 inhibitor, was assessed in patients with unresectable advanced exocrine adenocarcinoma of the pancreas. Methods: The study employed a two-stage design. Randomised first-line patients received BI 2536 200 mg on day 1 ( n =43) or 60 mg on days 1–3 ( n =43) every 21 days. Recruitment of second-line patients was planned for a second stage dependent on an interim analysis demonstrating ⩾2 responses in the first 18 evaluable patients following 12 weeks of treatment and/or tumour control ⩾12 weeks in 5 patients per schedule. Primary end point was objective response rate (ORR). Results: By independent review, ORR was 2.3% (all partial) and 24.4% had stable disease as confirmed best response. The second stage was not initiated. Median overall and progression-free survivals were 149 (95% confidence interval (CI), 91–307) and 46 days (95% CI, 44–56). Most common drug-related adverse events were neutropenia (37.2%), leukopenia (29.1%), fatigue (29.1%) and nausea (22.1%); most common grade 3/4-related events were neutropenia (36.0%), leukopenia (27.9%) and thrombocytopenia (8.1%). Conclusion: Given the low ORR and poor survival, further development of BI 2536 monotherapy is not warranted in this population.