Osimertinib plus chemotherapy in epidermal growth factor receptor (EGFR) L858R-mutant non-small cell lung cancer (NSCLC) with an indeterminate transient intracranial lesion: a case report

Patients with EGFR L858R-mutant non-small cell lung cancer (NSCLC) and baseline brain metastases have shorter progression-free survival on osimertinib monotherapy than those with other epidermal growth factor receptor (EGFR) mutations. The FLAURA2 trial showed that adding platinum-pemetrexed chemotherapy to osimertinib improves outcomes in this subgroup. However, the significance of a solitary new intracranial lesion during otherwise effective therapy remains uncertain. We report a 53-year-old male with EGFR L858R-mutant (allelic frequency 74.55%) lung adenocarcinoma, EGFR copy number gain (5 copies), and multiple brain metastases. After five cycles of first-line osimertinib plus carboplatin and pemetrexed, he achieved systemic partial response, but a new solitary right parietal nodule appeared on MRI. Without changing therapy, we continued osimertinib with close surveillance. Follow-up MRI at 4 months showed regression of this lesion with decreased T2-FLAIR (fluid-attenuated inversion recovery) signal and no enhancement. Here we show that a solitary new intracranial imaging abnormality during otherwise effective osimertinib-based therapy does not invariably establish treatment resistance. In carefully selected asymptomatic patients with controlled systemic disease, short-interval repeat imaging may be a reasonable alternative to immediate intervention, although the possibility that such lesions are not metastatic must be considered. Key findings: What is known and what is new: