Temsirolimus in Patients With Solid Tumors With PIK3CA Mutations: Results From the Targeted Agent and Profiling...

TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations who have no standard treatments available. Results of four cohorts of patients with PIK3CA-mutated tumors treated with temsirolimus are reported: breast cancer (BC), colorectal cancer (CRC), uterine cancer (UC) and other solid tumors (histology-pooled [HP]).

Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks duration. For the histology-specific cohorts, Simon's two-stage design was based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). For the HP cohort, the hypothesized null DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points were OR, progression-free survival, overall survival, duration of response, duration of SD, and safety.

Patients with PIK3CA-mutated BC (N = 12), CRC (N = 11), UC (N = 30), or other advanced cancers (HP cohort; N = 30) were enrolled. The BC and CRC cohorts did not reach the criteria to expand to stage II and were closed for futility. The DC rates with one-sided 90% CI were 37% (23 to 100, P = .0074) and 31% (20 to 100) for the UC and HP cohorts, respectively. The null hypothesized 15% DC rate was rejected for the UC and HP cohorts but not for the BC and CRC cohorts. Twenty-nine of 83 patients (35%) experienced treatment-related grade 3 adverse events (AEs) or serious AEs.

Temsirolimus demonstrated antitumor activity in patients with PIK3CA-mutated cancer within the UC and HP cohorts but not the BC or CRC cohorts.