TY - JOUR
T1 - Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma
AU - Wick, Wolfgang
AU - Puduvalli, Vinay K.
AU - Chamberlain, Marc C.
AU - Van Den Bent, Martin J.
AU - Carpentier, Antoine F.
AU - Cher, Lawrence M.
AU - Mason, Warren
AU - Weller, Michael
AU - Hong, Shengyan
AU - Musib, Luna
AU - Liepa, Astra M.
AU - Thornton, Donald E.
AU - Fine, Howard A.
PY - 2010/3/1
Y1 - 2010/3/1
N2 - Purpose: This phase III open-label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma (WHO grade 4). Patients and Methods: Patients were randomly assigned 2:1 to receive 6-week cycles of enzastaurin 500 mg/d (1,125-mg loading dose, day 1) or lomustine (100 to 130 mg/m2, day 1). Assuming a 45% improvement in progression-free survival (PFS), 397 patients were required to provide 80% power to achieve statistical significance at a one-sided level of .025. Results: Enrollment was terminated at 266 patients (enzastaurin, n = 174; lomustine, n = 92) after a planned interim analysis for futility. Patient characteristics were balanced between arms. Median PFS (1.5 v 1.6 months; hazard ratio [HR] = 1.28; 95% CI, 0.97 to 1.70), overall survival (6.6 v 7.1 months; HR = 1.20; 95% CI, 0.88 to 1.65), and 6-month PFS rate (P = .13) did not differ significantly between enzastaurin and lomustine, respectively. Stable disease occurred in 38.5% and 35.9% of patients and objective response occurred in 2.9% and 4.3% of patients, respectively. Time to deterioration of physical and functional well-being and symptoms did not differ between arms (HR = 1.12; P = .54). Four patients discontinued enzastaurin because of drug-related serious adverse events (AEs). Eleven patients treated with enzastaurin died on study (four because of AEs; one was drug-related). All four deaths that occurred in patients receiving lomustine were disease-related. Grade 3 to 4 hematologic toxicities were significantly higher with lomustine (46 events) than with enzastaurin (one event; P ≤ .001). Conclusion: Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.
AB - Purpose: This phase III open-label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma (WHO grade 4). Patients and Methods: Patients were randomly assigned 2:1 to receive 6-week cycles of enzastaurin 500 mg/d (1,125-mg loading dose, day 1) or lomustine (100 to 130 mg/m2, day 1). Assuming a 45% improvement in progression-free survival (PFS), 397 patients were required to provide 80% power to achieve statistical significance at a one-sided level of .025. Results: Enrollment was terminated at 266 patients (enzastaurin, n = 174; lomustine, n = 92) after a planned interim analysis for futility. Patient characteristics were balanced between arms. Median PFS (1.5 v 1.6 months; hazard ratio [HR] = 1.28; 95% CI, 0.97 to 1.70), overall survival (6.6 v 7.1 months; HR = 1.20; 95% CI, 0.88 to 1.65), and 6-month PFS rate (P = .13) did not differ significantly between enzastaurin and lomustine, respectively. Stable disease occurred in 38.5% and 35.9% of patients and objective response occurred in 2.9% and 4.3% of patients, respectively. Time to deterioration of physical and functional well-being and symptoms did not differ between arms (HR = 1.12; P = .54). Four patients discontinued enzastaurin because of drug-related serious adverse events (AEs). Eleven patients treated with enzastaurin died on study (four because of AEs; one was drug-related). All four deaths that occurred in patients receiving lomustine were disease-related. Grade 3 to 4 hematologic toxicities were significantly higher with lomustine (46 events) than with enzastaurin (one event; P ≤ .001). Conclusion: Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.
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U2 - 10.1200/JCO.2009.23.2595
DO - 10.1200/JCO.2009.23.2595
M3 - Article
C2 - 20124186
AN - SCOPUS:77949891455
SN - 0732-183X
VL - 28
SP - 1168
EP - 1174
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 7
ER -