Reference Detail

Ref Type

Journal Article

PMID

(26503204)

Authors

Hortobagyi GN, Chen D, Piccart M, Rugo HS, Burris HA, Pritchard KI, Campone M, Noguchi S, Perez AT, Deleu I, Shtivelband M, Masuda N, Dakhil S, Anderson I, Robinson DM, He W, Garg A, McDonald ER, Bitter H, Huang A, Taran T, Bachelot T, Lebrun F, Lebwohl D, Baselga J

Title

Correlative Analysis of Genetic Alterations and Everolimus Benefit in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From BOLERO-2.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology	34	5	2016 Feb 10	419-26	J Clin Oncol

URL

Abstract Text

To explore the genetic landscape of tumors from patients enrolled on the BOLERO-2 trial to identify potential correlations between genetic alterations and efficacy of everolimus treatment. The BOLERO-2 trial has previously demonstrated that the addition of everolimus to exemestane prolonged progression-free survival by more than twofold in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer previously treated with nonsteroidal aromatase inhibitors.Next-generation sequencing was used to analyze genetic status of cancer-related genes in 302 archival tumor specimens from patients representative of the BOLERO-2 study population. Correlations between the most common somatic alterations and degree of chromosomal instability, and treatment effect of everolimus were investigated.Progression-free survival benefit with everolimus was maintained regardless of alteration status of PIK3CA, FGFR1, and CCND1 or the pathways of which they are components. However, quantitative differences in everolimus benefit were observed between patient subgroups defined by the exon-specific mutations in PIK3CA (exon 20 v 9) or by different degrees of chromosomal instability in the tumor tissues.The data from this exploratory analysis suggest that the efficacy of everolimus was largely independent of the most commonly altered genes or pathways in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. The potential impact of chromosomal instabilities and low-frequency genetic alterations on everolimus efficacy warrants further investigation.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PIK3CA exon21	Her2-receptor negative breast cancer	no benefit	Everolimus	Phase III	Actionable	In a retrospective analysis of a Phase III trial (BOLERO-2), Afinitor (everolimus) demonstrated greater benefit on progression-free survival in patients with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring PIK3CA exon 10 (reported as exon 9) mutations (HR=0.26) compared to patients harboring PIK3CA exon 21 (reported as exon 20) mutations (HR=0.56) (PMID: 26503204; NCT00863655).	26503204
PIK3CA mutant	Her2-receptor negative breast cancer	no benefit	Everolimus	Phase III	Actionable	In a retrospective analysis of a Phase III trial (BOLERO-2), the presence of PIK3CA mutations did not significantly affect the efficacy of Afinitor (everolimus) in patients with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer, with a HR for progression-free survival of 0.37 in PIK3CA wild-type group and a HR of 0.51 (p=0.35) in patients with PIK3CA mutations (PMID: 26503204; NCT00863655).	26503204
PIK3CA exon10	Her2-receptor negative breast cancer	predicted - sensitive	Everolimus	Phase III	Actionable	In a retrospective analysis of a Phase III trial (BOLERO-2), Afinitor (everolimus) demonstrated greater benefit on progression-free survival in patients with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring PIK3CA exon 10 (reported as exon 9) mutations (HR=0.26) compared to patients harboring PIK3CA exon 21 (reported as exon 20) mutations (HR=0.56) (PMID: 26503204; NCT00863655).	26503204