Optimising primary molecular profiling in non-small cell lung cancer.

Area of Science:

• Oncology
• Molecular Diagnostics
• Genomics

Background:

• Molecular profiling is crucial for non-small cell lung cancer (NSCLC) treatment but is often incomplete.
• Standardized diagnostic procedures and protocolized profiling can optimize molecular testing in NSCLC.

Purpose of the Study:

• To assess the efficacy of protocolized molecular profiling within the standard-of-care for NSCLC in the Netherlands.
• To evaluate the impact of standardized diagnostic procedures on molecular profiling rates.
• To explore the utility of plasma-based molecular profiling in the primary diagnostic setting for NSCLC.

Main Methods:

• Prospective observational study with a run-in phase using local standard-of-care (SoC) tissue profiling.
• Subsequent phase involving protocolized comprehensive molecular profiling (CMP) to maximize testing rates (EGFR, ALK, PD-L1).
• Evaluation of centralized plasma-based testing (droplet digital PCR) for EGFR and KRAS mutations.

Main Results:

• Protocolized profiling increased EGFR and ALK testing rates from 69.9% to 77.0% in NSCLC patients.
• Significant improvements were observed in both non-squamous (77.9% to 82.1%) and squamous (43.8% to 57.5%) NSCLC.
• Plasma-based testing was feasible in 98.4% of cases and identified driver mutations in 7.1% of patients with unfeasible tissue profiling.

Conclusions:

• Protocolized tissue-based molecular profiling significantly enhances testing success rates in NSCLC.
• Tissue profiling remains unfeasible for a notable percentage of NSCLC patients.
• Combined analysis of tumor tissue and circulating tumor DNA (ctDNA) shows promise for achieving adequate molecular profiling in a larger patient cohort.