Long-term efficacy of osimertinib in de novo exon 19 deletion with T790M in an epidermal growth factor receptor mutated lung cancer patient in India

Abstract

Primary epidermal growth factor receptor (EGFR) T790M mutation is infrequently identified in previously untreated non-small cell lung cancer (NSCLC) patients. There is variation in the frequency of de novo T790M mutations depending on the population examined and the technology used for mutation detection. According to direct sequencing, 0.4–3% of all NSCLCs and 1–8% of all EGFR-mutant NSCLCs show primary T790M mutation. This mutation always coexists with a sensitizing EGFR mutation and is more commonly present along with exon 21 L858R mutation and infrequently with exon 19 deletion. Osimertinib, an oral irreversible third-generation EGFR tyrosine kinase inhibitor, is selective for both, EGFR sensitizing mutations and T790M resistance mutation. AURA trial has confirmed the effectiveness of osimertinib in patients with T790M mutation. The median progression-free survival is better in primary T790M as compared to the acquired mutation in a previously treated NSCLC. The overall survival with osimertinib is still 38.6 months only. Even after good response in both primary and acquired T790M mutation, there is disease progression and shifting to chemotherapy is required. We present an interesting case of a 60-year-old non-smoker female deriving benefit from a single agent osimertinib with a rare combination of mutation at presentation even after 6 years of initiation of therapy.