An exploratory analysis revealed that the efficacy of everolimus was independent of the most commonly altered genes or pathways in hormone-receptor positive human epidermal factor receptor 2-negative breast cancer, according to an article published online ahead of print in the Journal of Clinical Oncology.1
For this study, investigators sought to identify possible links between genetic alterations and efficacy of everolimus in patients enrolled in the BOLERO-2 trial. It had previously been established that the addition of everolimus to exemestane prolonged progression-free survival more than twofold in this patient population that had been previously treated with nonsteroidal aromatase inhibitors.
To investigate correlations between the most common somatic alterations and degree of chromosomal instability, researchers used next-generation sequencing to analyze the genetic status of cancer-related genes in 302 archival tumor specimens.
Results showed that progression-free survival in patients who were treated with everolimus was maintained regardless of alteration status of PIK3CA, FGFR1, and CCND1.
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Patient subgroups—defined by the exon-specific mutations in PIK3CA or by different degrees of chromosomal instability in tumor tissues—experienced quantitative differences in everolimus benefit.
Investigators concluded that further study is needed to assess the impact of chromosomal instabilities and low-frequency generic alterations on everolimus efficacy.
- Hortobagyi GN, Chen D, Piccart M, et al. Correlative analysis of genetic alterations and everolimus benefit in hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer: results from BOLERO-2 [published online ahead of print October 26, 2015]. J Clin Oncol. doi: 10.1200/JCO.2014.60.1971.