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.

Methods

• 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.

Results

• 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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