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28-10-2022 | Non-small-cell lung cancer | News

Real-world study adds support for osimertinib for uncommon EGFR mutations

Author: Shreeya Nanda


medwireNews: Osimertinib elicits high rates of systemic and intracranial response in people with advanced non-small-cell lung cancer (NSCLC) harboring uncommon EGFR mutations, say the authors of the real-world UNICORN study.

The study represents the “largest set” of NSCLC cases with uncommon mutations treated with osimertinib as the first EGFR–tyrosine kinase inhibitor, and the findings “further support” the use of osimertinib in these patients, they add.

UNICORN included data on 60 patients with advanced NSCLC and an uncommon EGFR mutation treated with osimertinib at one of 22 centers in nine countries. Participants were aged a median of 64 years and the majority were women (75%) and White (83%). The most frequent EGFR mutations in the cohort were G719X and L861Q, in 30% and 20%, respectively.

A total of 15 patients had compound mutations including a common EGFR mutation or de novo T790M mutation and one patient had just a de novo T790M mutation. The remaining 44 participants had no common or T790M mutations.

In this latter subgroup, the objective response rate (ORR) with osimertinib was 60%, while the median progression-free survival (PFS) and overall survival (OS) durations were 8.6 and 22.1 months, respectively.

The researchers note that their data are comparable to those of the only prospective study of osimertinib in patients with uncommon mutations, the Korean KCSG-LU15-09 trial, which showed an ORR of 50% and a median PFS duration of 8.2 months.

For the subgroup with compound common or T790M mutations, the ORR was 61%, median PFS was 30.0 months, and median OS was 31.4 months.

“These results compare favorably to the results of osimertinib in patients with only common mutations,” write Jair Bar (Chaim Sheba Medical Center, Ramat Gan, Israel) and colleagues in the Journal of Thoracic Oncology.

“Our data therefore suggest that compound mutations that include a common mutation can be treated safely with osimertinib, similarly to single common mutations.”

Efficacy analysis by specific mutation showed that among participants with a single or compound G719X mutation, the ORR was 47%, median PFS was 8.8 months, and median OS was unreached. For those with a single or compound L861Q mutation, the ORR was 80%, median PFS was 16.0 months, and median OS was 26.3 months.

In the overall study cohort, 23 patients had brain metastases at presentation, and of these 13 were evaluable by RANO-BM criteria, which showed an intracranial ORR of 46%. Bar et al highlight that “only two of the six responders […] harbored common mutations (L858R and T790M) as compound with an uncommon mutation.”

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J Thorac Oncol 2022; doi:10.1016/j.jtho.2022.10.004