The study is perfomed with adult patients with non-small cell lung cancer treated with tyrosine kinase inhibitor. The objective is to collect repeated samples of blood from patients (starting) on a tyrosine kinase inhibitor, for liquid mutation testing, and pharmacokinetic analysis.

This is an observational study in pulmonary oncology patients treated with TKI. Ideally before start of therapy, at week 4, 8 12, and then every 4-8 weeks (following the standard of care clinical pathways local guidelines) extra tubes of blood will be collected during blood withdrawal planned for standard-of-care. When a TKI switch takes place, patients receive a new study number and the blood collection will be continued following standard-of-care. Sampling will be performed during steady-state in working hours before next ingestion of TKI (the regular morning dose will need to be postponed until after blood withdrawal).

The moment of blood withdrawal after start of therapy and after last dosage of TKI will be registered.

At the time of progression the current standard of care is to perform a rebiopsy, to identify the resistance mechanism and determine the next appropriate systemic therapy for a patient. Some mechanisms can only be determined on a biopsy specimen (e.g. transformation to SCLC, MET amplification FISH). This study is observational and will not interfere with the current standard practice, therefore the treating physician is free to determine the indication for and possibility of a rebiopsy. However, when a biopsy is taken as standard of care, we will also draw an extra blood sample on the day of the biopsy (preferably during standard preprocedural coagulation status laboratory investigations) and use a portion of the biopsy for a fresh frozen specimen, as evolving molecular investigations (like RNA analysis) often need fresh non-fixed material to obtain reliable results.

Four to five core biopsies will be obtained for further analysis. Half of the obtained biopsy material will be stored in formalin according to local standard procedures, while the other half will be fresh frozen according to local standard procedures and stored for further analysis.

When the treating physician needs to take additional tissue or liquid (e.g. pleural fluid, liquor) for investigations following standard-of-care protocols, we would like to perform additional molecular and/or pharmacokinetic analysis on the residual material when applicable.

Inclusion Criteria:

• Age ≥ 18 years
• Able to understand the written informed and able to give informed consent
• Locally advanced or metastatic NSCLC with oncogenic driver mutation
• Treatment with TKI according to standard of care

Exclusion Criteria:

• Unable to draw blood for study purposes

Adult patients with non-small cell lung cancer treated with a tyrosine kinase inhibitor