TEST:

AVENIO ctDNA Expanded Kit

In case of low EGFRm VAF in plasma, combining tumor and plasma sequencing uncovers additional RMs compared to any single modality. Utilizing both for complete RM assessment is therefore recommended.

No significant differences in baseline ctDNA levels, changes at progression, or mutation patterns were observed between OP and SP. Although ctDNA levels generally decreased early after the start of ICI treatment, and were increased at disease progression, mutational profiles of the 77 genes using the AVENIO Expanded ctDNA panel did not distinguish OP from SP.

AVENIO identified additional actionable alterations, including ESR1 (17.5%) and PI3K pathway alterations (40.6%), and together with tumor fraction estimation, improved interpretation of negative liquid biopsy findings. These findings support broader ctDNA profiling in clinical practice while highlighting accessibility challenges.

ctDNA testing to detect oncogenic fusions or METexon14 mutations in advanced NSCLC patients is useful, even if type of gene alterations and clinical characteristics could influence the driver detection rate. Liquid biopsy represents a complementary tool to tissue genotyping, however more sensitive approaches for gene fusions and METexon14 detection are needed to implement its strength and reliability.

There was a high level of agreement between the Guardant360 CDx test and the ODxT test. The Guardant360 CDx test demonstrated analytical and clinical validity for identifying patients with HER2m NSCLC for T-DXd therapy; results support plasma-based testing when tissue-based testing is not feasible.

Based on our CGP and WGS approach for ctDNA analyses of hormone receptor positive mBC, we can elucidate distinct features of NST vs ILC in early lines of treatment, including the mutational profile, a significantly higher number of SNVs in ILC and distinct focal chromosomal aberrations. Additional analyses may improve diagnoses, treatment monitoring and understanding the underlying biology and resistance evolution of these clinically and molecularly distinct diseases.

However, clinical trials have been predominantly carried out with selected populations and single drugs (Palbociclib, Ribociclib or Abemaciclib). At baseline, and considering the pre-defined criteria, ctDNA analysis detected PIK3CA mutations in 32.25% and 44.44% of patients by AVENIO and ddPCR, respectively. ESR1 mutations were detected in 3.22% and 9.37% by AVENIO and ddPCR, respectively. For PIK3CA mutations, the Kappa value was 0.62 (p-value: 0.0004) and 0.47 for ESR1 mutations (p-value: 0.0039).

Combining plasma sequencing and tumor biopsy analysis uncovers additional resistance mechanisms compared to a single modality approach, highlighting the importance of combining both modalities for a complete assessment of resistance mechanisms and associated treatment options.

Additionally, HER2-0 patients had a significantly higher number of detected clonal variants than HER2-low patients. The mutational landscape revealed differences from previous reports, indicating that further investigations are needed to elucidate and establish the distinct features of HER2-low breast tumors.

Conclusions In ILC, PIK3CA, AR, and EGFR alterations and higher z-scores were more common but did not reach statistical significance. The numbers of SNV were significantly higher in patients with ILC.

In 2017, the Roche Cobas® EGFR Mutation Test v2 for the detection of the EGFR c.2369C>T p.(T790M) mutation in plasma-derived ctDNA was FDA-approved to identify patients eligible for osimertinib treatment...This implies that centralization of cfDNA-testing is necessary to optimize cost-efficiency. With the advent of ctDNA analysis beyond EGFR in the context of targeted therapies for lung cancer, multigene detection assays will become more cost-effective with high throughput.

The present study confirms the potential of liquid biopsy to detect tumour molecular heterogeneity in NSCLC patients at the diagnosis and at PD, demonstrating that a significant number of druggable mutations and mechanisms of resistance can be detected by NGS analysis on ctDNA.