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• W3136757034 abstract "Osimertinib is an oral, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used in treatment of advanced EGFR-mutant (EGFRm+) non-small cell lung cancer (NSCLC). We describe the clinicopathological characteristics and clinical outcomes of advanced EGFRm+ NSCLC patients treated with first-line osimertinib. We reviewed 66 consecutive Asian patients with advanced EGFRm+ NSCLC from the Lung Cancer Consortium Singapore database on first-line osimertinib. Clinical data including patient characteristics, concomitant mutations, presence of baseline brain metastases (BM), time-to-treatment failure and survival outcomes were retrospectively analyzed. All patients with adenocarcinoma histology were routinely tested for ALK, ROS 1, RET and cMET alterations/rearrangements by fluorescence-in-situ-hybridisation (FISH). Between June 2016 and October 2019, we identified 66 patients with advanced EGFRm+ NSCLC who were treated with first-line osimertinib. Median age of patients was 64 years (IQR 56-73), 65.2% were females, 75.8% never-smokers, and 90.9% with ECOG 0-1 at start of osimertinib. All had adenocarcinoma histology. Thirty-six (54.5%) patients harboured sensitizing EGFR exon 19 deletion (exon 19+) and 24 (36.4%) had exon 21 mutation (exon 21+). The remaining 6 had exon 20 mutation (exon 20+) co-existing with either exon 19+ (3.0%) or exon 21+ (6.1%). Among those with exon 20+, 5 were p.T790M and 1 p.S768I mutation. Baseline BM were present in 36 (54.5%) patients, of which 9 (25%) received radiotherapy (RT) to BM before starting osimertinib. Eight (12.1%) patients tested positive for cMET-polysomy (defined as ratio of MET to CEP 7 <2.0 with ≥5 copies of MET gene per nucleus), 48 (72.7%) negative for cMET polysomy/amplification and 10 (15.2%) unknown cMET. One patient had RET-rearrangement. PD-L1 status was known in 48 patients (72.8%) with 37 low PD-L1 tumor proportion score (TPS) <50% and 11 high PD-L1 (TPS ≥50%). Investigator-assessed response rate (RR) was 83% (95% CI 72.1-91.4%) – same regardless of presence/absence of baseline BM and exon 19+ or exon 21+. After median follow-up of 22 (95% CI 17.3-25.0) months, median progression-free survival (PFS) for all patients was 16.7 (95% CI 13.17-20.93) months and TTF 18.8 (95% CI 16.76-25.49) months. PFS for exon 19+ patients was 17.1 (95% CI 14.49-22.31) months and 11.0 (95% CI 8.02-22.70) months for exon 21+ (p=0.1). Median overall survival (OS) was 30.7 mths (95% CI 21.68-not estimable) but not yet mature. CNS disease progression (PD) occurred in 13 (20%) patients, of which 12/13 had baseline BM and 2/12 had RT to baseline BM before starting osimertinib. By univariable analysis, ECOG ≥2 was significantly associated with shorter PFS (HR 2.61, p=0.03) and MET-polysomy with shorter TTF (HR 3.33, p=0.01). PD-L1 status was not significantly associated with PFS. Patients with baseline BM and exon 21+ had significantly higher risk of CNS PD compared with those without baseline BM (33.3% vs 3.3%, p=0.002) and with exon 19+ (37.5% vs 11.1%, p=0.03), respectively. Osimertinib is an effective first-line treatment in Asian patients with advanced EGFRm+ NSCLC with durable OS, PFS and TTF. Despite good responses in patients with baseline BM and exon 21 mutation, additional treatment strategies are needed to improve their CNS outcomes." @default.
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• W3136757034 date "2021-03-01" @default.
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• W3136757034 title "P76.46 First-Line Osimertinib in Asian Patients with Advanced EGFR-Mutant Lung Cancer" @default.
• W3136757034 doi "https://doi.org/10.1016/j.jtho.2021.01.1103" @default.
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