What is the Preferred Treatment Option for Patients with NSCLC Harboring Uncommon EGFR Mutations?

Almost half (43%) of patients with non-small cell lung cancer (NSCLC) and uncommon epidermal growth factor receptor (EGFR) mutations treated with the EGFR tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib, afatinib, or osimertinib in the first- or second-line setting had an objective response, according to the retrospective UpSwinG study.

“EGFR TKIs are standard of care for patients with EGFR mutation-positive [NSCLC] with common mutations (Del19 or L858R); however, 7%-23% of NSCLC tumors harbor uncommon EGFR mutations,” wrote lead author Sanjay Popat, MBBS, PhD, Royal Marsden National Health Service Foundation Trust, London, UK, and co-authors.

In the global, multicenter study, researchers identified existing health records for 246 consecutive patients from 9 countries with uncommon EGFR mutations (such as T790M and ex20ins), major uncommon mutations (eg, G719X, L861Q, or S768I), or compound mutations. A maximum of 15 consecutive patients per site were included.

Almost all (92%) participants received an EGFR TKI as first-line therapy. Of the cohort, 54%, 43% and 3% received afatinib, first-generation TKIs, and osimertinib, respectively. Over half (56.9%) received more than 1 line of therapy. Most (84%) of the participants were Asian, and 7% had brain metastases at the time of diagnosis.

The median time to treatment failure (TTF) and overall survival (OS) were 9.9 and 24.4 months. Outcomes were most favorable in patients with major uncommon or compound mutations. TTF was 11.3 months for those who received afatinib, and 8.8 months for those who received first-generation EGFR TKIs across mutation categories. However, in 20 patients treated with first-line chemotherapy, median TTF was 6.6 months. In most mutation categories, median OS was >2 years.

Source:
Popat S, Hsia T, Hung J, et al. Tyrosine Kinase Inhibitor Activity in Patients with NSCLC Harboring Uncommon EGFR Mutations: A Retrospective International Cohort Study (UpSwinG). Oncologist. 2022 Apr 5;27(4):255-265. doi:10.1093/oncolo/oyac022.