2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.12A.05 Evaluation of the Role of VAF/cellularity as Proxy of Gene Aberration in EGFR Mutated Advanced NSCLC During Osimertinib

EP.12A.05 Evaluation of the Role of VAF/cellularity as Proxy of Gene Aberration in EGFR Mutated Advanced NSCLC During Osimertinib

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The study conducted by Marta Brambilla and colleagues from the 'Fondazione IRCCS Istituto Nazionale dei Tumori' in Milan, Italy, investigates the use of the Variant Allele Frequency (VAF)/cellularity ratio as a marker for genetic aberrations in patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations, under Osimertinib treatment. This research aimed to assess if VAF/cellularity could provide a more precise indication of treatment efficacy compared to traditional VAF measurements.<br /><br />The retrospective trial involved patients from the APOLLO 11 study and included those with cytological or histological diagnoses of advanced NSCLC, harboring common EGFR mutations like exon 19 deletions or the L858R exon 21 point mutation, who received at least one cycle of Osimertinib as a first-line treatment.<br /><br />Patients were categorized into cohorts based on the median and third quartile of their VAF/cellularity ratios. The study utilized next-generation sequencing (NGS) to analyze genetic profiles, focusing on seven specific genes and including comprehensive panels for wider genetic variants.<br /><br />The primary objective was to determine the difference in progression-free survival (PFS) according to the median VAF/cellularity, while an exploratory objective assessed PFS differences according to the third quartile VAF/cellularity.<br /><br />Results indicated that a higher VAF/cell ratio could be a reliable indicator of genomic imbalance, suggesting potential outcomes during Osimertinib treatment. High VAF/cell ratios may point to tumors with EGFR aberrations, such as loss of heterozygosity or copy number gains, which could predict poorer responses to treatment.<br /><br />Ultimately, the study concludes that VAF/cell might better predict tumor clonality and could serve as a significant surrogate marker for genetic aberrations in EGFR-mutated advanced NSCLC during Osimertinib therapy.

Asset Subtitle

Marta Brambilla

Meta Tag

Speaker Marta Brambilla

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

Variant Allele Frequency

VAF/cellularity ratio

non-small cell lung cancer

NSCLC

EGFR mutations

Osimertinib treatment

progression-free survival

genetic aberrations

next-generation sequencing

tumor clonality