A comprehensive prognostic analysis of osimertinib treatment in advanced non-small cell lung cancer patients with acquired EGFR-T790M mutation: a real-world study

Purpose: Osimertinib is the standard treatment for advanced non-small cell lung cancer (NSCLC) patients with T790M mutation after the failure of first-/second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). We comprehensively analyzed factors that affect the therapeutic efficacy of the osimertinib treatment in NSCLC patients.

Methods: 351 NSCLC patients with T790M mutation receiving osimertinib treatment were included. We investigated the value of different factors in predicting the clinical outcomes of the osimertinib therapy, including progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Logistic and COX regression were used to identify prognosticators.

Results: In osimertinib therapy, EGFR mutation status (19Del/L858R) at initial diagnosis and the therapeutic choice of prior EGFR-TKI agent was not associated with patients' prognosis. Notably, the PFS of the prior EGFR-TKI was independently related to ORR (OR, 95% CI 0.98, 0.96-1.00, p = 0.030), PFS (HR, 95% CI 0.98, 0.97-1.00, p = 0.009) and OS (HR, 95% CI 0.96, 0.93-0.98, p < 0.001) of osimertinib treatment. Among distinct organ metastases, only bone metastasis was related to the efficacy of osimertinib, in terms of ORR (OR, 95% CI 1.97, 1.27-3.06, p = 0.002), PFS (HR, 95% CI 1.55, 1.18-2.03, p = 0.001) and OS (HR, 95% CI 1.81, 1.27-2.59, p = 0.001). However, the therapeutic efficacy of osimertinib was not further impacted by the accumulation of metastatic organs. A performance status score of 2-4 was also an adverse prognosticator for the osimertinib therapy.

Conclusion: PFS of the prior EGFR-TKI treatment, performance status score and bone metastasis were independent prognosticators of the osimertinib treatment. These findings may facilitate clinicians in the decision-making of osimertinib.