Osimertinib a potential option for NSCLC with uncommon EGFR mutations
medwireNews: Individuals with advanced non-small-cell lung cancer (NSCLC) harboring uncommon EGFR mutations have favorable outcomes in response to osimertinib treatment, say Korean researchers.
They explain that uncommon EGFR mutations “are a highly heterogeneous group of molecular alterations within exons 18 to 21” that are present in about 20–25% of NSCLC patients with EGFR mutations.
The phase 2 trial (KCSG-LU15-09) included 36 patients with metastatic or recurrent NSCLC positive for any EGFR mutations other than the exon 19 deletion, L858R, T790M, or exon 20 insertion. The most common alteration in the cohort was G719X, observed in 53% of patients, followed by L861Q and S768I in 25% and 22%, respectively.
Treatment with the third-generation EGFR–tyrosine kinase inhibitor at a daily dose of 80 mg elicited an objective response in 50% of participants during a median follow-up of 20.6 months. All responses were partial and lasted for a median of 11.2 months.
Median progression-free survival (PFS) was 8.2 months, with PFS rates at 6 and 12 months of 64% and 39%, respectively, while median overall survival was unreached at time of analysis and 86% of participants were alive at 12 months and 56% at 18 months.
“This high response rate and long PFS are clinically meaningful given that uncommon EGFR mutations constitute a heterogeneous group of genetic alterations,” write Myung-Ju Ahn (Sungkyunkwan University School of Medicine, Seoul) and colleagues in the Journal of Clinical Oncology.
When stratified by mutation, the highest objective response rate was observed among individuals with the L861Q mutation, at 78%, followed by rates of 53% and 38% in those with the G719X and S768I mutation, respectively. The corresponding median PFS durations were 15.2, 8.2, and 12.3 months.
“The safety profile of osimertinib in this study was quite acceptable and mostly confined to grade 1 to 2 AEs [adverse events], which is consistent with previous reports,” says the team.
Rash (31%), pruritus (25%), anorexia (25%), diarrhea (22%), and dyspnea (22%) were the most frequent any-grade AEs, and only two patients experienced an AE of grade 3 or 4 – one case each of grade 3 dyspnea and grade 3 headache.
The osimertinib dose was reduced for just one patient and no participants discontinued as a result of AEs.
In light of the small sample size and the heterogeneity of the participants, Ahn and colleagues stress the need for additional larger trials, but conclude that “osimertinib can be considered as a treatment option for patients with NSCLC with uncommon EGFR mutations on the basis of this study.”
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