Abstract
The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results from cohorts of patients with metastatic breast cancer (BC) with
and
alterations treated with sunitinib are reported.
Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease of at least 16 weeks duration (SD16+) according to RECIST v1.1. Secondary end points included OR, progression-free survival, overall survival, duration of response, duration of stable disease, and safety.
Forty patients with BC with
(N = 30; amplification only n = 26, mutation only n = 1, both n = 3) or
(N = 10; amplification only n = 2, mutation only n = 6, both n = 2) alterations were enrolled. Three patients in the
cohort were not evaluable for efficacy; all patients in the
cohort were evaluable. For the
cohort, two patients with partial response and four with SD16+ were observed for DC and OR rates of 27% (90% CI, 13 to 100) and 7% (95% CI, 1 to 24), respectively. The null hypothesis of 15% DC rate was not rejected (
= .169). No patients achieved DC in the
cohort (
= 1.00). Thirteen of the 40 total patients across both cohorts had at least one grade 3-4 adverse event or serious adverse event at least possibly related to sunitinib.
Sunitinib did not meet prespecified criteria to declare a signal of antitumor activity in patients with BC with either
or
alterations. Other treatments and clinical trials should be considered for these patient populations.