Falchook G, et al. - In this open-label phase 1 trial of 191 patients and randomized phase 2 clinical trial of 142 patients with recurrent ovarian cancer or advanced breast cancer, researchers evaluated the activity of alisertib in combination with weekly paclitaxel in patients with breast (phase 1) and ovarian cancer (phase 1 and phase 2). As per outcomes, alisertib plus paclitaxel had more favorable progression-free survival (PFS) outcomes compared to paclitaxel alone.

Methods

• At 33 sites (United States, France, and Poland), researchers conducted an open-label phase 1 and randomized phase 2 clinical trial, from April 16, 2010, for phase 1 and March 28, 2012, to August 12, 2013, for phase 2.
• They reported data from a cutoff date of August 12, 2014, with a median duration of follow-up of 7.2 months and 4.6 months in the alisertib plus paclitaxel arm and the paclitaxel arm, respectively.
• Enrollment of a total of 191 women with advanced breast (phase 1 only) or recurrent ovarian cancer was done; these included 142 patients randomized to alisertib plus paclitaxel (n = 73) or paclitaxel alone (n = 69) in the phase 2 study.
• Randomization (1:1) of patients, who were stratified by platinum-free interval (refractory, 0-6 months, 6-12 months) and prior weekly taxane treatment (yes, no), was done to receive alisertib 40 mg twice per day orally and 3 days on and 4 days off for 3 weeks, plus paclitaxel (60 mg/m² intravenously, days 1, 8, and 15), or weekly paclitaxel 80 mg/m² intravenously in 28-day cycles.
• PFS was assessed as primary endpoint.
• Modified intention to treat (mITT) population was used for primary efficacy analysis and safety analysis (all randomized patients who received ≥1 dose of study drug).

Results

• In phase 1, 191 patients were enrolled [ median age was 59 (range, 29-75) years].
• In phase 2, the median age for the 142 patients enrolled was 63 (range, 30-81) years for patients receiving alisertib plus paclitaxel and 61 (range, 41-81) years for patients receiving paclitaxel.
• At data cutoff, a documented PFS event was noted for 107 (75%) patients; 52 (71%) in the alisertib plus paclitaxel arm, and 55 (80%) in the paclitaxel arm.
• Findings revealed median PFS of 6.7 months with alisertib plus paclitaxel vs 4.7 months with paclitaxel (HR, 0.75; 80% CI, 0.58-0.96; P=.14; 2-sided P value cutoff = .20 to be considered worthy of further investigation).
• Researchers noted drug-related grade 3 or higher adverse events in 63 (86%) vs 14 (20%) patients in the alisertib plus paclitaxel and paclitaxel arms, including 56 (77%) vs 7 (10%) neutropenia, 18 (25%) vs 0 stomatitis, and 10 (14%) vs 2 (3%) anemia; 54 (74%) vs 17 (25%) had adverse events leading to dose reductions.
• During the study, 2 patients died (1 in each arm); neither death was considered related to study drug.