Published in:
01-04-2015 | Original Article
Parallel phase Ib studies of two schedules of buparlisib (BKM120) plus carboplatin and paclitaxel (q21 days or q28 days) for patients with advanced solid tumors
Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2015
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Purpose
Phosphatidylinositol-3-kinase I (PI3K) inhibition sensitizes a wide range of cancer cell lines to platinum/taxane-based chemotherapy. This phase I study combines buparlisib, a pan-class 1A PI3K inhibitor, with two schedules of carboplatin and paclitaxel for patients with advanced solid tumors (ClinicalTrials.gov, NCT01297452).
Methods
There were two regimens: Group 1 received carboplatin AUC 5 and paclitaxel 175 mg/m2, on day 1 of a 21-day cycle with pegfilgrastim support; Group 2 received carboplatin AUC 5 (day 1) and paclitaxel 80 mg/m2 (days 1, 8, and 15) on a 28-day cycle without growth factor support. In both groups, three dose levels of buparlisib were explored: 50, 80, and 100 mg/day. Primary endpoint was to identify recommended phase II doses of buparlisib in both groups.
Results
Thirty subjects enrolled, 16 in Group 1 and 14 in Group 2. The DLTs were elevated alkaline phosphatase (n = 1) and uncomplicated neutropenia (n = 2). The median numbers of cycles were 5 (Group 1) and 6 (Group 2). The MTDs for buparlisib were 100 mg/day in Group 1 and 80 mg/day in Group 2. Among 25 patients with measurable disease, the confirmed objective response rate was 20 % (one complete response, four partial responses). Among three patients with known loss of PTEN expression, all derived clinical benefit from treatment.
Conclusion
The addition of buparlisib to carboplatin + paclitaxel was well tolerated, and preliminary activity was notable against tumors with loss of PTEN expression.