TEST:

cobas® EGFR Mutation Test v2

P3, N=587, Active, not recruiting, AstraZeneca | Trial completion date: Jun 2026 --> Dec 2026

P=N/A, N=130, Recruiting, Istituto Oncologico Veneto IRCCS | Trial completion date: Jul 2025 --> Jan 2026 | Trial primary completion date: Jul 2025 --> Jan 2026

P3, N=216, Active, not recruiting, AstraZeneca | Trial completion date: Jun 2026 --> Apr 2027

In January 2020, he began combination therapy with atezolizumab, bevacizumab, carboplatin, and paclitaxel. Given the clinical presentation, a driver gene mutation was strongly suspected. NGS identified the rare mutation pT751_I759delinsS, and the findings suggested the potential efficacy of osimertinib for this variant.

Limertinib showed superior efficacy compared with gefitinib and a manageable safety profile for locally advanced or metastatic NSCLC patients with EGFR-sensitising mutation and should be considered as another first-line treatment option for this patient population.

Most tissue specimens were adequate for EGFR testing. Inadequacy was commonly due to insufficient tissue volume or tumor content and higher in biopsies versus resections, and unresectable stage III and first-line advanced/metastatic versus other disease stages. Based on these controlled trial data, pre-analytic variables of tissue specimens are a major driver of testing success; hence maintaining optimal conditions from sample collection to biomarker analysis, as well as improving tissue-sampling techniques is critical to increase testing success rates.

These findings suggest that EGFR amplification, rather than specimen inadequacy, is the cause of low IC Ct results, making rebiopsy unnecessary. Alternative assays or diluted DNA allow for successful EGFR testing.

The variability in the genotyping methods and the success rate obtained in our study highlight the importance of EQA in Spain to ensure high performance.

For cancer prediction recurrence and treatment monitoring, ctDNA analysis can detect MRD earlier than conventional imaging, offering potential benefits for treatment adjustment and early relapse detection. The continuous development and validation of liquid biopsy methods are essential for improving personalized lung cancer treatment strategies.

Our preclinical, structural, and clinical findings indicate 2nd-generation EGFR-TKIs are more effective for EGFRex19ins compared to other TKIs.

Liquid biopsy is a transformative tool in NSCLC management, offering a minimally invasive approach for mutation detection, disease monitoring, and treatment guidance. Future research should focus on multicenter trials and emerging technologies to enhance clinical integration and broaden applicability across different cancer types.

There is no evidence of ctDNA or radiological disease relapse in the other three patients. Finally, a review of the literature addressing the potential value of MRD detection in this clinical setting is presented and discussed as well.