Olaparib in Patients With Solid Tumors With <i>BRCA1/2</i> Alterations: Results From The Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

Abstract

The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of targeted agents in patients with advanced cancer and genomic alterations. Results of five cohorts of patients with <i>BRCA1/2</i>-mutated solid tumors treated with olaparib are reported: breast cancer (BC), biliary tract cancer (BTC), lung cancer (LC), uterine cancer (UC), and other solid tumors (histology-pooled [HP]). Eligible patients had advanced 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 complete or partial response or stable disease (SD) of at least 16-weeks duration. For histology-specific cohorts, Simon two-stage design is based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). Cohorts that were closed before achieving the planned stage II sample size were analyzed using a one-sided exact binomial test. 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 objective response, progression-free survival, overall survival, duration of response or SD, and safety. Patients with BC (n = 28), BTC (n = 19), LC (n = 25), UC (n = 15), or other advanced cancers (n = 32) with <i>BRCA1/2</i> alterations were enrolled. The DC rates with one-sided 90% CI were 69% (55-100, <i>P</i> < .001), 50% (32-100, <i>P</i> = .0008), 41% (26-100, <i>P</i> = .0025), 47% (28-100, <i>P</i> = .0036), and 41% (29-100), respectively. The null hypothesized 15% DC rate was rejected for all cohorts. Thirty-six of 119 patients experienced treatment-related grade 3-4 adverse events (AEs) or serious AEs. Olaparib met prespecified criteria to declare a signal of activity in patients with various advanced <i>BRCA1/2</i>-altered solid tumors.