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Seung soo Yoo
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MA08 - Clinical Trials in Brain Metastases (ID 906)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 15:15 - 16:45, Room 203 BD
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MA08.07 - Real World Data of Osimertinib in Patients with Central Nervous System (CNS) Metastasis in ASTRIS Korean Subset. (ID 13581)
15:50 - 15:55 | Author(s): Seung soo Yoo
- Abstract
- Presentation
Background
More than 40% of non-small cell lung cancer (NSCLC) patients develop CNS metastasis in their lifetime. Osimertinib is a third-generation EGFR-TKI which selectively inhibits both EGFR-sensitizing and EGFR T790M resistance mutations. Clinical studies have shown superior efficacy of osimertinib in CNS compared to platinum chemotherapy. Treatment efficacy in patients with or without CNS metastasis were observed within the second interim analysis of ASTRIS (NCT02474355). Data cut-off (DCO) was 20 October 2017.
a9ded1e5ce5d75814730bb4caaf49419 Method
In ASTRIS, advanced NSCLC patients with a locally confirmed T790M mutation, WHO performance status 0-2, prior EGFR-TKI therapy were enrolled. Patients with stable CNS metastases were allowed. The primary endpoint was overall survival (OS); other endpoints included investigator-assessed response rate (RR), progression-free survival (PFS), time to treatment discontinuation (TTD) and safety. These endpoints were also analyzed according to presence of CNS metastasis.
4c3880bb027f159e801041b1021e88e8 Result
A total of 466 patients received at least one dose of osimertinib 80mg from 31 Korean sites. CNS metastasis was evaluated in 310 patients and was present in 211 (68.1%) patients (CNS-met); 181 brain only, 1 leptomeningeal only, 29 both. 99 (31.9%) patients did not have CNS metastasis (CNS-no), and 155 patients were not evaluated (CNS-ne). At DCO, 236 patients (50.6%) were ongoing and median duration of exposure was 11.2 (0–19) months. In patients evaluable for response, defined as at least one dose of osimertinib and one response assessment, RR was 71.0% (320/451; 95% CI, 66.5–75.1): Patients with (N=211), without (N=99), and not-evaluated CNS metastasis (N=155) had RR of 68% (134/197; 95% CI, 61.0-74.5), 79.6% (78/98; 95% CI, 70.3-87.1), and 69.7% (108/155; 95% CI, 61.8-76.8), respectively. Median PFS was 12.4 months (95% CI, 11.1-13.6 months); 10.8 months (95% CI, 9.5-11.5) in CNS-met,11.0 months (95% CI, 9.2-14.5) in CNS-no, and 15.1 months (95% CI, 13.6-18.2) in CNS-ne. Median TTD was 16.5 months (95% CI, 14.1-NC); 11.2 months (95% CI, 9.4-14.8) in CNS-met, 14.7 months (95% CI, 12.2-NC) in CNS-no, and NC (95% CI, 15.5-NC) in CNS-ne. OS was not reached (data maturity: 19.7%). Serious adverse event (AE) regardless of causality were reported in 116 patients (24.9%) and AEs leading to death in 13 patients (2.8%). ILD/pneumonitis-like events were reported in 8 patients (1.7%), and QTc prolongation in 7 patients (1.5%).
8eea62084ca7e541d918e823422bd82e Conclusion
In ASTRIS Korean subset, patients with or without CNS metastasis had comparable efficacy outcome. This data continues to support osimertinib’s clinical benefit on EGFRm T790M NSCLC patients with CNS metastasis.
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P2.03 - Biology (Not CME Accredited Session) (ID 952)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.03-27 - Polymorphisms in Folate Metabolism Related Genes Affect the Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer (ID 12650)
16:45 - 18:00 | Author(s): Seung soo Yoo
- Abstract
Background
Cellular folate status influences the DNA stability and integrity, and many epidemiologic, animal and human studies suggest that folate status modulates carcinogenesis. This study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) in genes involved in folate metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC).
a9ded1e5ce5d75814730bb4caaf49419 Method
We genotyped 182 potentially functional SNPs in folate metabolism pathway in a discovery study involving 354 NSCLC patients who underwent curative surgery. A replication study was performed in an independent cohort of 428 patients.
4c3880bb027f159e801041b1021e88e8 Result
In the discovery set, 38 SNPs were significantly associated with survival outcomes in multivariate analyses. Among these, two SNPs (ALPL rs2242421G>A, MTHFD1L rs9397033A>T) were replicated in the replication set. In combined analysis, ALPL rs2242421G>A was significantly associated with better overall survival under a codominant model (adjusted hazard ratio [aHR] = 0.72, 95% confidence interval [CI] = 0.59-0.88, P = 0.002). MTHFD1L rs9397033A>T was significantly associated with worse disease-free survival under a recessive model (aHR = 1.45, 95% CI = 1.13–1.87, P = 0.004). In a luciferase assay, the rs2242421A allele showed significantly higher luciferase activity than the rs2242421G allele (P = 0.02) in H1299 cell lines. Consistently, the level of ALPL mRNA expression in tumor tissues increased as the number of A allele increased (P trend = 0.05).
8eea62084ca7e541d918e823422bd82e Conclusion
Our results suggest that the 2 SNPs, especially ALPL rs2242421G>A could be used as a biomarker for predicting the clinical outcomes of patients with early stage NSCLC.
6f8b794f3246b0c1e1780bb4d4d5dc53
