TEST:

AVENIO ctDNA Expanded Kit

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.

Detection of CTCs and CTECs could be the potential adjunct tool for the early finding of lung cancer. The cfDNA levels are associated with the tumor burden, rather than the CTCs or CTECs counts. Moreover, the poorly consistent mutations between ctDNA and tDNA require further exploration.

P=N/A; Recruiting --> Completed | N=30 --> 104

Conclusions We suggest cfDNA, CP and TRM as putative circulating predictive biomarkers to be monitored in eSCLC pts receiving ACE. These data will be confirmed in a wider validation set of pts with a longer FUP.

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...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.

Conclusions Our results suggest a significant difference in the tumor fractions in plasma between HER2-0 and HER2-low patients. Moreover, the mutational landscape of our cohort revealed differences from previous reports, indicating that further investigations are needed to elucidate and establish the distinct features of HER2-low breast tumors.

Conclusions The current SLR highlights the scarcity of real-world evidence on genetic alterations in A/M TNBC. Molecular subtyping exhibits a significant potential in identifying specific genetic alterations, emphasizing the need for further research and larger-scale studies.

Recently, we demonstrated that a high-resolution SiMSen-seq assay (SSS) provides a sensitive and robust method for detecting 11 PIK3CA hotspot mutations in cell-free circulating DNA, allowing the identification of patients eligible for alpelisib treatment... The AVENIO ctDNA Expanded Kit revealed a high sensitivity and concordance rate for detecting PIK3CA hotspot mutations in plasma samples compared with the high-resolution 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.

Conclusions In pts with BRAF V600E mt cancers treated with vemurafenib and erlotinib, baseline ctDNA profile and an early decline in ctDNA were predictive of clinical outcomes. ctDNA analyses provided a mechanistic understanding of intrinsic and acquired resistance, revealing frequent evidence of convergent evolution and MAPK pathway reactivation as the dominant mechanism of therapeutic escape.

Additionally, the cfDNA of 8 pts of C2 that progressed after 1L chemotherapy + panitumumab (C-P) was analyzed using next-generation sequencing (NGS) (AVENIO ® ctDNA expanded panel and Illumina NextSeq 550) containing 77 genes Results and Discussions A total of 65/64/58 (MAF ≥1/≥0.1/≥0.02% [C1]) and 45 (C2) pts were evaluable ( RAS wt at baseline as per solid and liquid biopsies and blood sample available at DP), of which 58/57/51 (C1) and 40 (C2) received C-P...However, a complex mutational process driving resistance is suggested based on NGS-cfDNA analysis. Further investigation in larger numbers of pts is warranted Study supported by Amgen S.A.

"The targeted capture sequencing test can support comprehensive molecular analysis needed for TKIs treatment, which is promising to be clinically applied for the improved precision treatment of NSCLC."