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Poster session 08

2261P - A head-to-head comparison for detecting PIK3CA mutations in circulating tumor DNA of advanced HR+/HER2- breast cancer patients

Date

21 Oct 2023

Session

Poster session 08

Topics

Translational Research;  Genetic and Genomic Testing

Tumour Site

Breast Cancer

Presenters

Nadia Dandachi

Citation

Annals of Oncology (2023) 34 (suppl_2): S1152-S1189. 10.1016/S0923-7534(23)01927-0

Authors

N. Dandachi1, R. Graf2, L. Pancheri1, N. Dobrić1, E.V. Klocker1, C. Suppan1, P.J. Jost1, E. Heitzer2, M. Balic1

Author affiliations

  • 1 Department Of Internal Medicine - Division Of Oncology, Medical University of Graz, 8036 - Graz/AT
  • 2 Institute Of Human Genetics, Diagnostic And Research Center For Molecular Biomedicine, Medical University of Graz, 8010 - Graz/AT

Resources

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Abstract 2261P

Background

Recently, we demonstrated that a high-resolution SiMSen-seq assay (SSS) provides a sensitive and robust method for detecting 11 PIK3CA hotspot mutations in ctDNA, allowing the identification of patients eligible for alpelisib treatment. Unfortunately, due to intrinsic or acquired resistance, most patients progress within months to years. Therefore, detecting additional genomic biomarkers for treatment resistance beyond PIK3CA mutations is crucial. Here we present interim results for our ongoing study to show that a commercial NGS assay (AVENIO ctDNA Expanded Kit, Roche Diagnostics) can detect PIK3CA mutations with similar high sensitivity as our high-resolution SSS assay.

Methods

37 HR+/HER2- patients were included before starting 1st line treatment and 30 before starting 2nd line treatment. Plasma samples were analyzed using SSS and the AVENIO assay. Additionally, mFAST-SeqS was used to estimate the tumor fractions in plasma samples.

Results

The median z-score from mFAST-SeqS analyses was 2.88 [25–75th percentile: 1.48–7.36], and 30/67 (45%) samples had z-scores >= 3, indicating elevated tumor fractions (>5%). Two samples were not evaluable with SSS, leaving 65 samples for a head-to-head comparison. 29 alterations were detected in 27 (41.5%) samples by the SSS assay and 31 in 28 samples (43.1%) by the AVENIO assay. Overall, we found an excellent concordance rate of 95.4% (62/65 samples) between the two assays, confirming the high sensitivity of the panel sequencing assay. Moreover, the VAF of SSS and AVENIO were highly correlated (Spearman’s rho = 0.93, p < 0.001).

Conclusions

The AVENIO ctDNA Expanded Kit revealed a high sensitivity and concordance rate for detecting PIK3CA hotspot mutations in plasma samples compared with the SSS assay. A major advantage of panel sequencing over a single-gene approach is that the interrogation of multiple genes can indicate a true negative PIK3CA result if other variants are present with a high VAF. Moreover, other actionable targets or mechanisms of resistance can be captured simultaneously, thus improving the effective precision treatment of metastatic breast cancer patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Medical University of Graz.

Funding

Novartis Pharma GmbH.

Disclosure

N. Dandachi: Financial Interests, Personal, Other, travel support: Daiichi Sankyo. E.V. Klocker: Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Novartis; Financial Interests, Personal, Other, Travel fee: Daiichi Sankyo, Gilead; Financial Interests, Institutional, Other, Travel fee: Pierre Fabre. C. Suppan: Financial Interests, Personal, Advisory Board: Lilly, Pfizer, Novartis, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Roche, Pierre Fabre, AstraZeneca. P.J. Jost: Financial Interests, Personal, Advisory Board: Bayer, Boehringer Ingelheim, Novartis, Pfizer, Servier; Financial Interests, Personal, Speaker’s Bureau: Bayer, Boehringer Ingelheim, Novartis, Pfizer; Financial Interests, Institutional, Research Funding: Boehringer Ingelheim, Novartis, BMS; Financial Interests, Personal, Speaker, Consultant, Advisor: Servier, Roche, BMS, Janssen, AstraZeneca, Merck, Sanofi- Aventis, Ipsen, Amgen. E. Heitzer: Financial Interests, Institutional, Research Funding: Servier, Freenome, PreAnalytixX; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche Diagnostics; Financial Interests, Institutional, Product Samples, Provision of reagents: Roche Diagnostics, Illumina. M. Balic: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Daiichi Sankyo, MSD, Pierre Fabre, Pfizer, Roche, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eli Lilly, Eli Lilly, MSD, Novartis, Novartis, Pierre Fabre, Pfizer, Roche, Gilead; Financial Interests, Personal and Institutional, Coordinating PI: AstraZeneca; Financial Interests, Personal, Coordinating PI, Steering Committee Member, Coordinating PI, Advisory role: Roche; Financial Interests, Institutional, Local PI: Roche, MSD, Qiagen, Amgen, Gilead; Financial Interests, Institutional, Coordinating PI: Austrian Breast and Colorectal Cancer Study Group, Pierre Fabre, Novartis, Pfizer. All other authors have declared no conflicts of interest.

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