OBJECTIVES: Lung cancer treatment remains challenging despite numerous available therapies. The progress of next-generation sequencing (NGS) technologies has raised huge expectations for precision-medicine approaches, but its success depends on the integration of genetic insights into clinical practice. This study aims to explore the relationship between metastatic non-small cell lung cancer (mNSCLC) diagnosis and Portuguese physicians' treatment decisions, focusing on the impact of genetic information on therapeutic choices.

METHODS: A nationwide representative panel composed of 11 medical experts with experience in the treatment of NSCLC completed an electronic questionnaire on clinical practices for diagnosing and treating mNSCLC patients. Stated preferences for treatment options in first, second and third-line were elicited according to the test used (IHC, FISH, DNA-NGS, DNA+ RNA-NGS, DNA sequencing, and RT-PCR) and genetic variants involved (ALK, BRAF V600, EGFR, EGFR exon20, HER2, METex14, NTRK, RET, ROS1). Data were analyzed for frequency and central tendency measures.

RESULTS: Most hospital centers test for genetic variants quite frequently (>70% for all variants), primarily through reflex testing in the initial assessment, regardless of disease stage (64-73%), with NGS of DNA and RNA being the preferentially used technique (60-73%).The preferred treatment sequence for patients with EGFR mutations is osimertinib (100%) in first-line followed by platinum-duplets in second-line (91%). EGFR exon 20 insertions are mostly treated with platinum-duplets in first-line (64%) followed by amivantab (55%). Upfront treatment for patients with ALK translocations is alectinib (73%) followed by lorlatinib (91%). First-line decision for ROS1 translocation, BRAF V600 mutation and RET translocation is crizotinib (91%), dabrafenib+trametinib (64%) and selpercatinib (64%), respectively. Additionally, MET exon14 skipping mutations receive platinum duplets+pembrolizumab (PD-L1<50%; 46%) followed by platinum-duplets or tepotinib (46% each).

CONCLUSIONS: At most of the Portuguese hospitals, the search for genetic variants and respective technique and timing of the test, as well as the therapeutic options used, generally follows ESMO’s recommendations.