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.
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%).


CONCLUSIONS
Given the low ORR and poor survival, further development of BI 2536 monotherapy is not warranted in this population.
Geschäftführender Oberarzt, Klinik für Tumorbiologie an der, Albert-Ludwigs Universität Freiburg, Breisacherstrasse 117, D-79106 Freiburg, Germany. mross@tumorbio.uni-freiburg.de
K
K
Mross
C
C
Dittrich
W E
WE
Aulitzky
D
D
Strumberg
J
J
Schutte
R M
RM
Schmid
S
S
Hollerbach
M
M
Merger
G
G
Munzert
F
F
Fleischer
M E
ME
Scheulen
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D000368:Aged; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015331:Cohort Studies; D016001:Confidence Intervals; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011621:Pteridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D000097869:Polo-Like Kinase 1; C518477:BI 2536