On December 10, 2019 Caris Life Sciences, a leading innovator in molecular science focused on fulfilling the promise of precision medicine, reported that it will present results from a study evaluating the prevalence of phosphatidylinositol-3-kinase (PI3K)/AKT/PTEN pathway alterations and co-alterations in patients with different subtypes of breast cancer. The molecular profiles of nearly 5,000 patients were evaluated using the Caris Molecular Intelligence Next-Generation Sequencing (NGS) technology, which identified pathogenic or presumed pathogenic mutations on the PI3K pathway using a 592-gene DNA sequencing panel.
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Results showed a high prevalence of hotspot mutations in PIK3CA and that 8% of breast tumors carry uncommon activating PIK3CA mutations. Additional genes activating the pathway including AKT1, PI3R1, PIK3R2 and PTEN were investigated and showed mutation rates ranging from 0.1% to 3%. In addition, the study revealed a significant increase in PD-L1 expression in tumor cells and high tumor mutational burden (TMB) in PIK3CA-AKT1-PTEN mutated cohorts.
The full results will be featured in Poster Session 4 on Friday, December 13, from 7:00-9:00 a.m. CT at the 2019 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas (Presentation #P4-09-04). The poster is titled, "Prevalence of phosphatidylinositol-3-kinase (PI3K) pathway alterations and co-alteration of other markers in breast cancer."
"PI3K and AKT inhibitors have been shown to have significant activity against tumor progression and to overcome resistance in breast cancer, and the recent advancement of the drug class to the clinical use in breast cancer is truly exciting," said investigator Filipa Lynce, M.D., an oncologist with Georgetown Lombardi Comprehensive Cancer Center and MedStar Georgetown University Hospital, a member of the Precision Oncology Alliance. "These results demonstrate a high incidence of common and uncommon mutations that activate PI3K pathway in these patients, which is meaningful for patient selection for the very promising drug class. The knowledge gained from this study on molecular alterations that co-occur with PI3K pathway activation could ultimately help identify novel drug combinations that have the potential to elicit synergistic growth inhibition."
Of the 4,895 molecular profiles submitted to Caris Life Sciences, 72.7% had at least one alteration in the PIK3CA-AKT1-PTEN pathway. PIK3CA was the most frequent alteration in HER2 positive breast cancer, and TNBC was the subtype with the lowest frequency of PIK3CA mutations (18.0% vs. 37% in other subtypes). Notable co-alterations in the TNBC cohort include increased PD-L1 expression high TMB and increased RAS signaling.
The Precision Oncology Alliance (POA) includes 31 academic, hospital and community-based cancer institutions, including nine NCI-designated Comprehensive Cancer Centers collaborating to further the understanding of molecular profiling. To date, the POA has presented over 100 abstracts and publications.
"Our data at SABCS 2019 continue to reinforce the need for further research in precision medicine in metastatic breast cancer care," said W. Michael Korn, M.D., Chief Medical Officer at Caris Life Sciences. "As the use of precision medicine continues to evolve, our ongoing work in tumor biology and biomarkers will have broad implications in helping to guide treatment decisions for patients across a range of tumor types, including breast cancer."