Challenges in the management of EGFR-mutated non-small cell lung cancer patients with acquired resistance to tyrosine kinase inhibitors.

Non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) mutation have a median progression-free survival of 12 months on treatment with tyrosine kinase inhibitors (TKIs). Clearly, the introduction of these agents had major implications for the treatment of NSCLC, but new questions and challenges arise as well. Traditionally, response assessments of anti-cancer treatment are conducted according to the RECIST criteria. Progressive disease is usually indicative of a change of therapy. In the current era of targeted therapies, it has become clear that different patterns of progressive disease are observed with TKI treatment in EGFR-mutated NSCLC patients, with potential consequences for therapeutic decision-making. In this review, we will discuss whether the RECIST criteria are still optimal for response evaluation. Rebiopsy studies have provided more insight into different resistance mechanisms at the time of acquired resistance to TKIs. These mechanisms, as well as the role of rebiopsy in daily clinical practice, will subsequently be covered. Finally, treatment strategies for different types of progressive disease will be discussed.