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

Purpose: 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. Experimental Design: 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 PIK3CA mutations. Adverse events (AEs) were recorded using NCI-CTCAE v4.0. Tumor response was investigator-determined using RECIST v1.1. Results: 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 sixty patients had evaluable tissue for central PIK3CA mutation testing (20 had mutations, 27 had no mutation detected [MND]). In patients with baseline measurable disease, clinical activity was observed in tumors with PIK3CA 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]), PIK3CA-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 PIK3CA 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]). Conclusions: Taselisib plus fulvestrant had clinical activity irrespective of PIK3CA mutation status, with numerically higher objective response rate and CBR in patients with PIK3CA-mutated (versus -MND) locally advanced or metastatic HER2-negative, HR-positive breast cancer. No new safety signals were reported. A confirmatory Phase III trial is ongoing.

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