Most educational sessions at the ELCC about EGFRm+ NSCLC began with the fact that the EGF receptor is a cancer driver in 10-15% of caucasian and up to 40% of Asian lung cancer patients has been known for decades. However, the selection of the right patients for EGFR inhibitors proved more difficult than first expected in the early 2000s. EGFR amplification was not the right biomarker but rather EGFR mutations as discovered several years later when the first EGFR TKI was fully approved for patients with EGFR activating mutations in/on their NSCLC cells. Some being extremely sensitive to EGFR tyrosine kinase inhibitors (TKIs) e.g. exon 19 deletions and others not at all e.g. mutations in exon 20 – at least not to first generation EGFR TKIs. The first EGFR TKIs are approved for almost 10 years in certain countries. Many patients benefited over the years. Not all of them are so called super-responders that still respond to the inhibitor after many years (some around 10). But with few exceptions, all patients with EGFR activating mutations do respond to EGFR TKIs for several months. Afterwards, sadly cancer cells are able to develop resistance mutations and tumors progress. Or clones with exon 20 mutations resulting for example in the T790M amino acid exchange or new driver mutations in different receptor pathways take over.
Since recently (2016), a so called third generation EGFR TKI is available for patients with T790M positive lung cancer. This molecule seems well engineered and the clinical outcome has astonished many if not all experts in the lung cancer field. As discussed prior in the posting about ALK inhibitors, many questions remain unanswered and will keep the research community occupied for several years: When and how to test patients? When to switch from one inhibitor to the other? How to sequence? Which inhibitor to use first? Can outcome even be improved or maybe even a cure achieved with a combination of EGFR TKIs plus another targeted therapeutic or immune therapy … the topic of the next posting.