Molecular profiling and immunotherapy in the real-life clinical setting in non-small cell lung cancer

Abstract

Modern treatment of non-small cell lung cancer (NSCLC) has evolved to include targeted therapy and immunotherapy. Because these treatments require specific genetic targets or PD-L1 expression, precise molecular profiling is essential.

The first two studies in this thesis investigated ways to optimize these diagnostics. One study showed that systematic, comprehensive profiling of tumor tissue can achieve success rates up to 91%. Both studies also evaluated circulating tumor DNA (ctDNA) from blood samples. This ‘liquid biopsy’ was successful in over 98% of cases. In metastatic NSCLC, ctDNA analysis reached over 75% sensitivity for identifying actionable targets, providing a vital alternative when tissue biopsies are unavailable.

The second part of the research focuses on immunotherapy efficacy. Analysis of pembrolizumab and nivolumab (the latter studied in a real-world cohort of 248 patients) showed significant survival benefits. For nivolumab, the 3-year survival rate was 17.1%, rising to 55.3% for those who responded to treatment. Adverse events were generally mild and manageable.

Ultimately, optimizing molecular diagnostics through both tissue and blood analysis is crucial for delivering personalized, effective treatment to more NSCLC patients.