Osimertinib in uncommon exon 21 L861R and 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 () mutations. Whilst there have been a handful of case reports of sensitivity to first-generation TKIs in L861R mutations, the efficacy of the third-generation TKI osimertinib in NSCLC patients with L861R and exon 18 deletion-insertion mutations is limited.

Case Description: We report two patients from our institution with uncommon mutations treated with first-line osimertinib. Our first patient, a 72-year-old male with metastatic lung adenocarcinoma was identified to harbour a rare 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 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 L861R and exon 18 deletion-insertion mutations. These results may be suggestive of the wider applicability of osimertinib in the treatment of uncommon mutant NSCLC.