期刊
CANCER DISCOVERY
卷 12, 期 9, 页码 2058-2073出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-21-1696
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资金
- Cancer Council Victoria
- National Health and Medical Research Council
- Royal Australasian College of Physicians
- National Breast Cancer Foundation
- Peter MacCallum Cancer Centre
- Australian National Health and Medical Research Council Practitioner Fellowship
- CSL Centenary Fellowship and National Health and Medical Research Council Investigator [1196755]
- National Breast Cancer Foundation of Australia Endowed Chair
- Breast Cancer Research Foundation, New York
Alpelisib monotherapy demonstrated efficacy in heavily pretreated ER + breast cancer, and the dynamics of PIK3CA mutation and ESR1 mutation detected in plasma can serve as candidate biomarkers for predicting treatment response.
There is limited knowledge on the benefi t of the alpha-subunit-specifi c PI3K inhibitor alpe-lisib in later lines of therapy for advanced estrogen receptor-positive (ER +) HER2- and triple-negative breast cancer (TNBC). We conducted a phase II multicohort study of alpelisib monotherapy in patients with advanced PI3K pathway mutant ER +HER2- and TNBC. In the intention-to-treat ER +cohort, the overall response rate was 30% and the clinical benefi t rate was 36%. A decline in PI3K pathway mutant circulating tumor DNA (ctDNA) levels from baseline to week 8 while on therapy was signifi cantly associated with a partial response, clinical benefi t, and improved progression-free-survival [HR 0.24; 95% confi dence interval (CI), 0.083-0.67, P= 0.0065]. Detection of ESR1 mutations at baseline in plasma was also associ-ated with clinical benefi t and improved progression-free survival (HR 0.22; 95% CI, 0.078-0.60, P= 0.003). SIGNIFICANCE: Alpelisib monotherapy displayed effi cacy in heavily pretreated ER + breast cancer with PIK3CA mutations. PIK3CA mutation dynamics in plasma during treatment and ESR1 mutations detected in plasma at baseline were candidate biomarkers predictive of benefi t from alpelisib, high-lighting the utility of ctDNA assays in this setting.
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