PhD defence C.M.J. (Christi) Steendam

Summary:

The Epidermal Growth Factor Receptor (EGFR) is a protein on the cell that plays a role in lung cancer. In this thesis we explore innovations in optimizing treatment with EGFR inhibitors. The combination of the EGFR inhibitor erlotinib plus docetaxel chemotherapy showed detrimental results in a group of patients with normal EGFR compared to docetaxel alone. Furthermore, the toxic limit of the EGFR inhibitor osimertinib was determined, a dose adjustment could possibly prevent a large part of severe toxicity in the future. We investigated the effect of chemotherapy in patients with treatment with an EGFR inhibitor in the past because of an activating mutation. Treatment with several chemotherapy regimens adds another substantial period of disease control.

In the next part detection of tumor DNA in blood was explored. Two new techniques were compared (ddPCR and NGS), both showed to be able to detect mutations adequately. Then blood was examined in a group of patients in whom DNA analysis of tissue was not possible. NGS was able to detect targets for therapy that would not have been known otherwise. Furthermore, blood was analyzed over time in a group op patients with an EGFR mutation. The results were less favorable when EGFR mutations present in the blood at the start of medication were not cleared over a period of treatment.