Research on the efficacy of first-line osimertinib in non-small cell lung cancer (NSCLC) patients with different epidermal growth factor receptor (EGFR) exon 19 deletion (19del) mutation sites is limited. This study aimed to evaluate whether different EGFR 19del subtypes are associated with differential clinical outcomes in patients with EGFR-mutant NSCLC receiving first-line osimertinib therapy. This study included 106 NSCLC patients with stage IIIb–IV disease from the CAPTRA-Lung database, confirmed to have EGFR 19del mutations through next-generation sequencing (NGS) and receiving first-line osimertinib. Patients were categorized based on mutation frequencies (common E746A750del mutation or other uncommon subtypes), the deletion start codon for the EGFR 19del (E746 or L747), and the number of deleted nucleotides (15-nucleotide deletion 15n-del or non-15n-del). Clinical characteristics, objective response rate (ORR) and progression-free survival (PFS) were compared between these subgroups. A total of 19 EGFR 19del mutation subtypes were identified. The most frequent mutation site for exon 19 deletion was E746A750del, accounting for 56. 6% of cases (n = 60), followed by L747P753delinsS (9. 4%, n = 10), L747T751delinsP (6. 6%, n = 7), and L747A750delinsP (4. 7%, n = 5). Patients in the non-15n-del group had a higher prevalence of baseline brain metastases compared with those in the 15n-del group (41. 7% vs. 22. 9%; P = 0. 044). No associations were found between ORR and PFS of first-line osimertinib treatment and mutation frequencies, the deletion start codon for the EGFR 19del, and the number of deleted nucleotides. However, certain subtypes, particularly L747A750delinsP, showed a trend toward a shorter PFS compared with the common E746A750del subtype, although these differences did not reach statistical significance (12. 3 months vs. 24. 3 months; P = 0. 100). Overall, EGFR 19del subtypes showed comparable responses to first-line osimertinib. However, the trend toward poorer outcomes in the L747A750delinsP subtype suggests potential heterogeneity that warrants confirmation in larger cohorts with longer follow-up.
Zhang et al. (Mon,) studied this question.