Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor-Positive Advanced Breast Cancer.

Abstract

<b>Purpose:</b> This single-arm, open-label phase II study evaluated the safety and efficacy of taselisib (GDC-0032) plus fulvestrant in postmenopausal women with locally advanced or metastatic HER2-negative, hormone receptor (HR)-positive breast cancer.<b>Patients and Methods:</b> Patients received 6-mg oral taselisib capsules daily plus intramuscular fulvestrant (500 mg) until disease progression or unacceptable toxicity. Tumor tissue (if available) was centrally evaluated for <i>PIK3CA</i> mutations. Adverse events (AE) were recorded using NCI-CTCAE v4.0. Tumor response was investigator-determined using RECIST v1.1.<b>Results:</b> Median treatment duration was 4.6 (range: 0.9-40.5) months. All patients experienced ≥1 AE, 30 (50.0%) had grade ≥3 AEs, and 19 (31.7%) experienced 35 serious AEs. Forty-seven of 60 patients had evaluable tissue for central <i>PIK3CA</i> mutation testing [20 had mutations, 27 had no mutation detected (MND)]. In patients with baseline measurable disease, clinical activity was observed in tumors with <i>PIK3CA</i> mutations [best confirmed response rate: 38.5% (5/13; 95% CI, 13.9-68.4); clinical benefit rate (CBR): 38.5% (5/13; 95% CI, 13.9-68.4)], <i>PIK3CA</i>-MND [best confirmed response rate: 14.3% (3/21; 95% CI, 3.0-36.3); CBR: 23.8% (5/21; 95% CI, 8.2-47.2)], and unknown <i>PIK3CA</i> mutation status [best confirmed response rate: 20.0% (2/10; 95% CI, 2.5-55.6); CBR: 30.0% (3/10; 95% CI, 6.7-65.2)].<b>Conclusions:</b> Taselisib plus fulvestrant had clinical activity irrespective of <i>PIK3CA</i> mutation status, with numerically higher objective response rate and CBR in patients with <i>PIK3CA</i>-mutated (vs. -MND) locally advanced or metastatic HER2-negative, HR-positive breast cancer. No new safety signals were reported. A confirmatory phase III trial is ongoing. <i>Clin Cancer Res; 24(18); 4380-7. ©2018 AACR</i>.