Clinical outcomes of patients taking first-generation EGFR-TKIs may predict the benefits afforded by osimertinib in EGFR T790M-mutant NSCLC patients.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are widely used to treat patients with EGFR-mutated non-small cell lung cancers (NSCLCs). The association between the clinical outcomes of patients on first-line EGFR-TKIs and the efficacy of osimertinib as second-line treatment has not been previously assessed. This is our topic here.

Patients And Methods: We retrospectively analysed 67 patients with EGFR mutations on osimertinib after treatment with first-generation EGFR-TKIs. We evaluated patient characteristics, the EGFR T790M allele frequency in plasma samples and clinical outcomes.

Results: When osimertinib was given as second-line treatment, the median progression-free survival (PFS) was 6.0 months, and the response rate and disease control rate were 32.8% and 91.0%, respectively. Correlation analysis showed that the female sex and isolated (not multiple) progression on first-line EGFR-TKIs were correlated with a superior response to osimertinib. Kaplan-Meier analysis showed that patients exhibiting a partial response, isolated progression, and longer PFS on first-line EGFR-TKIs experienced prolonged PFS on osimertinib. Univariate analysis indicated that the treatment response, PFS and progression when on first-line EGFR-TKIs affected the PFS on osimertinib. Multivariate analysis showed that progression when on first-line EGFR-TKIs was independently prognostic of a response to osimertinib. The median PFS of patients with isolated progressive disease PD alone who were receiving brain radiotherapy was significantly longer than that of patients with isolated progressive disease alone who did not receive brain radiotherapy as well as patients exhibiting multiple progression. A low frequency of the EGFR T790M allele in plasma tended to predict an inferior efficacy of osimertinib and shorter PFS.

Conclusion: We found that patients who benefited from first-line EGFR-TKIs may experience prolonged PFS and a higher response rate when subsequently given osimertinib. A low plasma frequency of the EGFR T790M allele may predict poor osimertinib efficacy and shorter PFS.