P2.01-80 Clinical Outcomes in Advanced EGFR-Mutant NSCLC Patients Treated with First-Generation EGFR TKIs Followed by Subsequent Osimertinib

Abstract

Treatment with first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) plus subsequent osimertinib is standard of care for advanced (EGFR)-mutant non-small cell lung cancer (NSCLC) harboring T790M mutation. However, few data are available that have assessed the cumulative survival benefit of sequential EGFR TKIs in patients with EGFR-mutant NSCLC with T790M mutations in ‘real-world’ clinical practice. We retrospectively identified advanced EGFR-mutant NSCLC patients treated with first-line EGFR TKIs plus subsequent osimertinib between January 27th, 2015 and December 1st, 2018 at our institute. Clinical outcomes were analyzed. Subsequent genetic profiling was performed at the time of progression by next-generation sequencing (NGS). The primary endpoint was overall survival (OS) calculated from first-line treatment start to death or the last follow-up, and the secondary endpoint was progression-free survival (PFS) with osimertinib defined as the time from the first dose of osimertinib to disease progression or death. Primary resistance to osimertinib was defined as PFS≤4 months for T790M-mutant patients treated with osimertinib. The last follow-up time was January 27th, 2019. Median follow-up time was 52.0 months (range, 9.0∼108.0 months). Among 117 eligible patients treated with first-line EGFR TKIs plus subsequent osimertinib, 96 had T790M mutation and 21 showed negative T790M mutation or unknown status at the baseline of osimertinib treatment. Median OS was significantly prolonged in T790M-mutant patients than those with negative/unknown T790M mutation (58.0 vs. 28.3 months, p<0.001). However, there was no significant difference in median PFS with osimertinib between the two groups. Furthermore, there was no significant difference in both median OS and PFS with osimertinib between the non-brain metastatic and brain metastatic groups (median OS, 58.0 vs. 54.8 months, p=0.840; median PFS, 11.8 vs. 9.1 months, p=0.145). Median OS was significantly shortened in patients (N=20) with primary resistance to osimertinib than those (N=72) with PFS>4 months (38.2 vs 54.8 months, p=0.027). In real-world clinical practice, treatment with first-generation EGFR TKIs plus subsequent osimertinib for T790M-mutant patients can significantly prolong OS than those with negative/unknown T790M mutation. However, survivals are similar between the patients with and without brain metastases at the baseline of osimertinib. OS is significantly shorter in those with primary resistance to osimertinib.Tabled 1Non-brain metastasis at the baseline (n=55)Brain metastasis at the baseline (n=41)P-valueOsimertinib PFS≤4m (n=20)Osimertinib PFS＞4m (n=72)P-valueSexMale21 (38.2%)20 (48.8%)0.2997 (35.0%)32 (44.4%)0.450Femal Age,years ≤55 >5534 (61.8%) 19(34.5%) 36(65.5%)21 (51.2%) 18(43.9%) 23(56.1%)0.35713 (65.0%) 9 (45.0%) 11(55.0%)40 (55.6%) 27(37.5%) 45(62.5%)0.543ECOG PS0-154(98,2%)38(92.7%)0.00020(100%)68(94.4%)0.2812-41(1.8%)3(7.3%)0(0%)4(5.6%)Histologyadenocarcinoma53 (96.4%)41 (100%)0.21718 (90.0%)72 (100%)0.007non-adenocarcinoma2 (3.6%)0 (0%)2 (10.0%)0 (0%) Open table in a new tab