Osimertinib in uncommon EGFR exon 21 L861R and EGFR exon 18 deletion-insertion mutant non-small cell lung cancer-case report.

Background: Tyrosine kinase inhibitors (TKIs) have changed the treatment landscape for patients with advanced non-small cell lung cancer (NSCLC) found to have oncogene-driven activating epidermal growth factor receptor ( EGFR ) mutations. Whilst there have been a handful of case reports of sensitivity to first-generation TKIs in EGFR L861R mutations, the efficacy of the third-generation TKI osimertinib in NSCLC patients with EGFR L861R and EGFR exon 18 deletion-insertion mutations is limited.
Case Description: We report two patients from our institution with uncommon EGFR mutations treated with first-line osimertinib. Our first patient, a 72-year-old male with metastatic lung adenocarcinoma was identified to harbour a rare EGFR L861R mutation and was commenced on osimertinib. After a follow-up period of 18 months, the patient is continuing to experience treatment benefit with imaging showing a good partial response. The second patient, a 60-year-old male also with metastatic lung adenocarcinoma and an EGFR exon 18 deletion-insertion mutation achieved a partial response for 6.6 months. Upon progression, he was commenced on carboplatin and pemetrexed chemotherapy however died from subsequent pneumonia. He had an overall survival (OS) from time of diagnosis of 7.6 months.
Conclusions: We demonstrate clinical efficacy of first-line osimertinib in the treatment of advanced NSCLC harbouring uncommon EGFR L861R and EGFR exon 18 deletion-insertion mutations. These results may be suggestive of the wider applicability of osimertinib in the treatment of uncommon EGFR mutant NSCLC.
Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-788/coif). S.A. reports speaker fees from Merck-Sharpe & Dohme, Astra Zeneca, Roche, Bristol-Myers Squibb; travel support from Astra Zeneca, Roche, Merck-Sharpe & Dohme; non-financial aid from Astra Zeneca, Pfizer; and Advisory Boards of Boehringer Ingelheim, Roche. The other authors have no conflicts of interest to declare.
(2024 Translational Lung Cancer Research. All rights reserved.)