Rechallenge with erlotinib in osimertinib-resistant lung adenocarcinoma mediated by driver gene loss: a case report

The efficacy and safety of osimertinib have been demonstrated in several clinical trials; however, acquired resistance is an inevitable problem associated with most targeted drugs. Based on previous findings, the mechanism of osimertinib resistance is equivocal, and there is still no consensus on the most optimal treatment strategy after developing resistance, especially for patients detected with no actionable driver mutation. Here, we report the efficacy of erlotinib rechallenge in a patient with advanced lung adenocarcinoma following osimertinib resistance mediated by driver gene loss. Following osimertinib resistance, targeted sequencing of both blood and tissue samples revealed the disappearance of both EGFR exon 19 deletion and T790M. Erlotinib was then re-administered, achieving partial response for 26 months at least. Our case provides clinical evidence supporting the efficacy of erlotinib rechallenges in overcoming osimertinib resistance mediated by driver gene loss, which may translate into novel treatment strategies for lung cancer patients following development of resistance to osimertinib.