Real-world efficacy of osimertinib in previously EGFR-TKI treated NSCLC patients without identification of T790M mutation

Background The efficacy of osimertinib in previously EGFR-TKI-treated NSCLC without identification of T790M mutational status remains unclear in real-world practice. Patients and methods 417 patients had stage III-IV NSCLC harboring EGFR mutation and 154 out of 417 patients receiving osimertinib as >= second-line EGFR-TKI were identified. The time to treatment failure and risk of death were analyzed. Results Higher risk of death was found in EGFR-mutant patients with age >= 65 years, non-adenocarcinoma, no surgery or radiation, non-exon 19 deletion/exon 21 L858R, higher ECOG PS (2-4), PD-L1 expression >= 50%, and bone/liver/adrenal metastasis (all p < 0.05). Osimertinib as >= second-line TKI in patients with/without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib (p = 0.0002; 0.0232, respectively). However, osimertinib-treated patients with T790M did not have superior survival than those without (p = 0.2803). A higher risk of treatment failure for osimertinib was found in males, patients with first-line TKI duration <= 12 months, BMI drop > 10%, and PD-L1 expression >= 50% (All p < 0.05). Nonetheless, osimertinib as >= second-line TKI in patients without identification of 790 M did not have higher risk of treatment failure than those with T790M (p = 0.1236). Conclusions This study demonstrates that osimertinib as second line or subsequent TKI in EGFR-TKI-treated patients without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib, in real-world practice. Additionally, EGFR-mutant patients with PD-L1 expression >= 50% had a higher risk of treatment failure for osimertinib and worse overall survival than those with PD-L1 expression < 50%. These results suggest that osimertinib as second line or subsequent TKI may be a potential alternative option for the treatment of patients without identification of T790M and PD-L1 expression >= 50% is associated with a significantly poor outcome in patients receiving osimertinib.

Automated summary

This study demonstrates that osimertinib as a second or subsequent line of treatment in patients previously treated with EGFR-TKIs without identification of T790M mutation showed a lower risk of death compared to those who received first-line or second-generation TKIs without subsequent osimertinib. Patients with EGFR mutations and PD-L1 expression >= 50% had a higher risk of treatment failure with osimertinib and worse overall survival. These results suggest that osimertinib as a second-line or subsequent treatment may be a potential alternative for patients without identification of T790M, while high PD-L1 expression is associated with poor outcomes in patients receiving osimertinib.