Title : Treatment challenges for EGFR-mutant NSLC and LMD: When adverse reactions prevent targeted therapy
Abstract:
Purpose: To review the optimal treatment of EGFR-mutant non-small cell lung cancer (NSCLC) that has progressed to leptomeningeal disease (LMD) through a rare case presentation and literature review.
Background: LMD, the spread of cancer into the leptomeninges, is a rare complication of NSCLC with a median survival of 4-6 weeks without treatment. The risk of LMD among patients with NSCLC is 1-10%. In some cases, EGFR mutations T790M and L858R are targetable by Osimertinib, a brain-penetrant third-generation tyrosine kinase inhibitor (TKI). However, Osimertinib can induce cancer cell selection for various escape mechanisms. Newer agents which act on the EGFR extracellularly and at the tyrosine kinase domain may be beneficial in these cases. We present a case of EGFRmut NSCLC with LMD for which Osimertinib is contraindicated due to an adverse reaction, and we discuss the literature supporting newer agents for treatment of EGFRmut NSCLC with LMD.
Methods: We received the patient’s consent to present this case. PubMed was used for the literature review. Relevant imaging was obtained from the electronic medical record.
Results: A 69-year-old right-handed woman presented with worsening memory following whole brain radiotherapy (WBRT) for calvarial metastases from EGFRmutant NSCLC. Screening MRI with gadolinium revealed LMD. Serum testing with Guardant 360 had previously confirmed L858R and T790M mutations in EGFR, and PDL-1 expression was < 1%. She developed interstitial lung disease (ILD) following the first dose of Osimertinib a few weeks prior to LMD diagnosis. She was therefore started on Amivantamab, a bispecific antibody targeting cMET and EGFR, and
intrathecal topotecan.
Conclusion: The current case highlights the challenges of treating EGFR-mutant NSCLC in the CNS with limited targeted therapeutic options. Our patient developed TKI-induced ILD after one dose of Osimertinib, which is a black box warning for rechallenge with this agent. WBRT was unavailable after LMD diagnosis due to prior radiation exposure. While the new cMET/EGFR- targeting Amivantamab shows promising systemic disease control after failure of Osimertinib, it does not cross the blood-brain barrier. To date, no IT studies have been done with Amivantamab. Lazertinib is a new oral TKI which improves overall survival and progression-free survival among patients with brain metastases from EGFRmut NSCLC. However, the risk of ILD reactivation in the current setting is unknown, and the efficacy of Lazertinib in LMD is also unknown. Further research regarding the efficacy of Amivantamab and Lazertinib in the setting of an LMD resulting from EGFR-mutant NSCLC is needed.
