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.

Abstract

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.

• Authors: K Mross, C Dittrich, W E Aulitzky, D Strumberg, J Schutte, R M Schmid, S Hollerbach, M Merger, G Munzert, F Fleischer, M E Scheulen
• Journal: British journal of cancer (Br J Cancer) Vol. 107 Issue 2 Pg. 280-6 (Jul 10 2012) ISSN: 1532-1827 [Electronic] England
• PMID: 22699824 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• BI 2536
• Cell Cycle Proteins
• Proto-Oncogene Proteins
• Pteridines
• Protein Serine-Threonine Kinases

Topics

• Adenocarcinoma (drug therapy, enzymology, metabolism)
• Aged
• Cell Cycle Proteins (antagonists & inhibitors, metabolism)
• Cohort Studies
• Confidence Intervals
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms (drug therapy, enzymology, metabolism)
• Protein Serine-Threonine Kinases (antagonists & inhibitors, metabolism)
• Proto-Oncogene Proteins (antagonists & inhibitors, metabolism)
• Pteridines (adverse effects, pharmacokinetics, therapeutic use)
• Polo-Like Kinase 1