EGFR rearrangement

PE cfDNA genotyping has clinical applicability for NSCLC patients and can serve as an additional source for molecular testing. Incorporating PE NGS cfDNA analysis into genetic testing enhances diagnostic yield and aids in identifying actionable mutations in clinical practice.

Finding and confirming these biomarkers is essential for improving early detection, tracking the course of the disease, and directing focused treatments. As research progresses, combining molecular, genetic, and environmental insights might improve lung cancer care, prevention, and early diagnosis, thereby lowering the disease's worldwide burden.

Consequently, we conducted a review of relevant literature, summarizing the clinicopathological and molecular characteristics of CMPT to facilitate further research. Our insights enhance the understanding of this uncommon tumor and contribute to the expansion of its molecular alteration spectrum.

P1, N=275, Recruiting, Seagen Inc. | Not yet recruiting --> Recruiting

Variant-specific PCR was performed for 744 tumors with a normal 5'/3'-end expression ratio: there were no rearrangements in 172 EGFR/ALK/ROS1/RET/MET-negative lung cancers and 125 pediatric tumors, while NTRK3 fusions were detected in 2/447 (0.5%) non-lung adult malignancies. In conclusion, this study describes a diagnostic pipeline that can be used as a cost-efficient alternative to conventional methods of NTRK1-3 analysis.

P1b/2, N=196, Completed, Syndax Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Jul 2023 --> Sep 2022

PRESSING-HER2 panel and HER2 non-amplified status by NGS warrant validation as potential predictive markers in this setting.

P1, N=275, Not yet recruiting, Seagen Inc.

Variant-specific PCR was performed for 744 tumors with normal 5'/3'-end expression ratio: there were no rearrangements in 172 EGFR/ALK/ROS1/RET/MET-negative lung cancers and 125 pediatric tumors, while NTRK fusions were detected in 2/447 (0.4%) non-lung adult malignancies. Conclusions This study describes a robust pipeline for the detection of NTRK1, NTRK2 and NTRK3 gene fusions, which may be considered as a cost-efficient alternative to conventional methods of NTRK analysis.

Notably, (+)-8l significantly suppressed tumor growth in the H1975 cell-inoculated xenograft model (20 mg/kg/d, TGI: 96.11%), PC9 cell-inoculated xenograft model (20 mg/kg/d, TGI: 96.61%) and EML4 ALK-Baf3 cell-inoculated xenograft model (30 mg/kg/d, TGI: 80.86%). These results highlight the differentiated potential of (+)-8l to inhibit ALK rearrangement and EGFR mutation in NSCLC.

SHERLOCK enabled rapid, sensitive, and variant-specific detection of BCR::ABL1 and EGFR alterations. Compared with the gold-standard PCR-based methods currently used in clinic, SHERLOCK achieved equivalent to greater sensitivity, suggesting it could be a new tool in CML and NSCLC, to detect low level of molecular residual disease.

In the probabilistic sensitivity analysis, 90% of the simulations performed showed that is adjuvant atezolizumab is cost-effective versus BSC considering a threshold of €30,000/QALY. Our results showed that adjuvant treatment with atezolizumab in patients with early-stage resected NSCLC with overexpression of PD-L1 and without EGFR and ALK mutations is cost-effective versus BSC as the ICERs and ICURs obtained are below the cost-effectiveness thresholds commonly considered in Spain, thus offering a new treatment alternative for these patients.