Abstract
OBJECTIVE: Osimertinib is the standard targeted strategy for lung adenocarcinoma patients harboring epidermal growth factor receptor (EGFR)-activating mutation who have achieved acquired mutation T790M beyond progression of first-line EGFR-tyrosine kinase inhibitor (TKI). In a real world setting, the efficacy for osimertinib as a subsequent treatment beyond first-generation EGFR-TKI progression under complex circumstances such as different T790M mutation status is still worth exploring. METHODS: Records of 84 lung adenocarcinoma patients with an EGFR sensitive mutation who received first-generation EGFR-TKI as first-line therapy and sequenced by osimertinib after progression were retrospectively reviewed in this study. The assessment of efficacy of subsequent osimertinib treatment was evaluated by progression free survival (PFS), objective response rate (ORR), complete response (CR), partial response (PR), disease control rate (DCR) and stable disease (SD) rates. Relationship between PFS and clinicopathological characteristics was analyzed using univariate analysis. RESULTS: Until the median follow-up time of 23.7 months (IQR 10.8-29.0 months), the median PFS (mPFS) of subsequent osimertinib was 17.0 months (HR 1.744, 95% CI, 13.547-20.382). Among 60 patients who had at least one measurable lesion, 35.0% of patients (21/60) had PR to osimertinib, and 63.3% patients (38/60) had SD during osimertinib treatment. The ORR was 35.0%, and the DCR was 98.3%. Patients with acquired T790M mutation which was detected by NGS or ddPCR assay had an mPFS of 17.0 months (HR = 1.032, 95% CI, 14.941-18.987), while the remaining 17 patients who had negative or unknown T790M mutation status had an mPFS of 23.5 months (HR = 9.404, 95% CI, 5.068-41.932). No significant difference was observed in those with and without T790M mutation (P = 0.704). CONCLUSION: Osimertinib may serve as an alternative subsequent choice after progression of first-generation EGFR-TKI in EGFR-mutated lung adenocarcinoma and may represent a potential treatment option for selected T790M-negative patients.