Phase II study of taselisib (GDC-0032) in combination with fulvestrant in patients with HER2-negative, hormone receptor-positive advanced breast cancer Journal Article


Authors: Dickler, M. N.; Saura, C.; Richards, D. A.; Krop, I. E.; Cervantes, A.; Bedard, P. L.; Patel, M. R.; Pusztai, L.; Oliveira, M.; Cardenas, A. K.; Cui, N.; Wilson, T. R.; Stout, T. J.; Wei, M. C.; Hsu, J. Y.; Baselga, J.
Article Title: Phase II study of taselisib (GDC-0032) in combination with fulvestrant in patients with HER2-negative, hormone receptor-positive advanced breast cancer
Abstract: 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. Patients and Methods: 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 (AE) were recorded using NCI-CTCAE v4.0. Tumor responsewas investigator-determined using RECIST v1.1. Results: Median treatment duration was 4.6 (range: 0.940.5) 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 PIK3CA mutation testing [20 had mutations, 27 had no muta-tion 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 (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. (C) 2018 AACR.
Keywords: placebo; endocrine therapy; double-blind; controlled-trial; multicenter; postmenopausal women; advanced solid tumors; dose-escalation; comprehensive molecular portraits; pi3k inhibitor
Journal Title: Clinical Cancer Research
Volume: 24
Issue: 18
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2018-09-15
Start Page: 4380
End Page: 4387
Language: English
ACCESSION: WOS:000444768200007
DOI: 10.1158/1078-0432.ccr-18-0613
PROVIDER: wos
PMCID: PMC6139036
PUBMED: 29793946
Notes: Article -- Source: Wos
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MSK Authors
  1. Maura N Dickler
    237 Dickler
  2. Jose T Baselga
    396 Baselga