A double-blind, randomized, placebo-controlled, phase 2 study of maintenance enzastaurin with 5-fluorouracil/leucovorin plus bevacizumab after first-line therapy for metastatic colorectal cancer
Wolff RA et al. – Enzastaurin combined with bevacizumab–based therapy is tolerable, but does not improve progression–free survival (PFS) during maintenance therapy in patients with metastatic colorectal cancer (MCRC) compared with bevacizumab–based therapy alone.
Patients with locally advanced or MCRC and stable or responding disease after completing 6 cycles of first-line chemotherapy randomly received a loading dose of enzastaurin 1125mg, followed by 500mg/d subsequent doses or placebo.
Both arms received 5-fluorouracil/leucovorin (leucovorin 400mg/m2 intravenously [IV], 5-fluorouracil 400-mg/m2 bolus, 5-fluorouracil 2400mg/m2 IV) plus bevacizumab 5mg/kg IV, every 2weeks.
The primary endpoint was progression-free survival (PFS), from randomization.
Overall survival (OS) and PFS were also assessed from start of first-line therapy.
Enrollment was stopped, and the final analysis was conducted after 73 PFS events.
Fifty-eight patients were randomized to enzastaurin and 59 to placebo.
For the enzastaurin and placebo arms, respectively, the median cycles received were 9 and 10, and the median PFS was 5.8 and 8.1months (hazard ratio [HR], 1.35; 95% confidence interval [CI], 0.84-2.16; P=.896).
Median OS was not calculable because of high censoring (77.6% enzastaurin; 91.5% placebo).
The median PFS from start of first-line therapy was 8.9months for enzastaurin and 11.3months for placebo (HR, 1.39; 95% CI, 0.86-2.23; P=.913).
More enzastaurin patients developed thrombosis or embolism compared with placebo (15.8% and 1.7%; P=.008).
One possibly enzastaurin-related death occurred because of arrhythmia.
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