MA15.10 Loss of T790M Mutation is Associated with Early Progression to Osimertinib in Chinese Advanced NSCLC Patients Harboring EGFR T790M

e21563 Background: Osimertinib is standard of care for patients with advanced non–small-cell lung cancer (NSCLC) carrying acquired epidermal growth factor receptor ( EGFR) T790M mutation. However, few studies have been conducted to investigate the impact of rebiopsy on clinical outcomes after resistance to osimertinib. We evaluated whether next-generation sequencing (NGS) of tissue and liquid rebiopsy could favor post-progression outcomes of T790M-positive advanced NSCLC patients treated with osimertinib. Methods: Immediately just after resistance to second- or further-line osimertinib, advanced NSCLC patients with acquired EGFR T790M mutation were retrospectively divided into the NGS and non-NGS groups according to whether they underwent NGS of tissue or liquid rebiopsy. The co-primary endpoints were post-progression survival (PPS) defined as the time from osimertinib resistance to subsequent-line treatment resistance, and post-progression overall survival (pOS) defined as from osimertinib resistance to death or end of the last follow-up. Multivariable analyses were done using Cox proportional hazards regression model and log-rank test. Results: Between January 2017 and July 2019, 89 patients (62 vs. 27 for the NGS and non-NGS groups respectively) were eligible for final analyses. In the NGS group, 3.2% (2/62) underwent tissue rebiopsy only, 29.0% (18/62)only had liquid rebiopsy, and 66.8% (42/62)with both tissue and liquid rebiopsy.The NGS group received more targeted or combined therapy after resistance to osimertinib (62.9% vs. 40.8%, P= 0.053). The NGS group was significantly superior to the non-NGS group in the co-primary endpoints. The median PPS was 6.1 vs. 2.7 months (hazard ratio [HR], 0.49; 95%CI, 0.30 to 0.80; 2-sided log-rank P= 0.004). Meanwhile, the median pOS was 11.7 vs. 6.8 months (HR, 0.50; 95%CI, 0.29 to 0.85, 2-sided log-rank P= 0.009). Conclusions: Providing more opportunities for individualized treatment, NGS of tissue and liquid rebiopsy favors post-progression outcomes of EGFR T790M-positive advanced NSCLC patients treated with osimertinib.

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P2.03-040 EGFR T790M Mutation Detection and Osimertinib Treatment Response Evaluation by Liquid Biopsy in Advanced NSCLC Patients

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2017.09.1291 ◽

2017 ◽

Vol 12 (11) ◽

pp. S2142-S2143 ◽

Cited By ~ 1

Author(s):

C. Li ◽

H. Liu ◽

B. Zhang ◽

Z. Zhang ◽

Y. Su ◽

...

Keyword(s):

Treatment Response ◽

Liquid Biopsy ◽

Mutation Detection ◽

Advanced Nsclc ◽

Response Evaluation ◽

T790m Mutation ◽

Treatment Response Evaluation ◽

Nsclc Patients ◽

Egfr T790m

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Efficacy and Acquired Resistance of EGFR-TKI Combined with Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Non-Small Cell Lung Cancer in a Real-world Setting

10.21203/rs.3.rs-121107/v1 ◽

2020 ◽

Author(s):

Qianqian Wang ◽

Wen Gao ◽

Fangyan Gao ◽

Shidai Jin ◽

Tianyu Qu ◽

...

Keyword(s):

Egfr Mutation ◽

Advanced Nsclc ◽

Acquired Resistance ◽

Small Cell ◽

Combination Group ◽

Monotherapy Group ◽

Small Cell Lung ◽

T790m Mutation ◽

Nsclc Patients ◽

Egfr Tki

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting.Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity.Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.674-23.326] vs. 11.70 months [95% CI, 10.807-12.593], p = 0.000). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.300-41.700) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

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Real Clinical Practice of Using Afatinib Therapy in NSCLC Patients with an Acquired EGFR T790M Mutation

Anticancer Research ◽

10.21873/anticanres.12871 ◽

2018 ◽

Vol 38 (9) ◽

pp. 5409-5415 ◽

Cited By ~ 1

Author(s):

KUNIHIKO MIYAZAKI ◽

TOMOHIRO TAMURA ◽

TAKAYUKI KABURAGI ◽

KAZUHITO SAITO ◽

MASAHARU INAGAKI ◽

...

Keyword(s):

Clinical Practice ◽

T790m Mutation ◽

Nsclc Patients ◽

Egfr T790m ◽

Real Clinical Practice

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Clinical Characteristics of Osimertinib Responder in Non-Small Cell Lung Cancer Patients with EGFR-T790M Mutation

Cancers ◽

10.3390/cancers11030365 ◽

2019 ◽

Vol 11 (3) ◽

pp. 365 ◽

Cited By ~ 2

Author(s):

Akihiro Yoshimura ◽

Tadaaki Yamada ◽

Naoko Okura ◽

Takayuki Takeda ◽

Kazuki Hirose ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Kinase Inhibitors ◽

Small Cell ◽

Small Cell Lung ◽

T790m Mutation ◽

Nsclc Patients ◽

Egfr T790m ◽

Egfr Tkis

Osimertinib is a mutant-selective EGFR inhibitor that is effective against non-small cell lung cancer (NSCLC) in patients with the EGFR-T790M mutation, who are resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, the factors affecting response to osimertinib treatment are unknown. In this retrospective study, 27 NSCLC patients with the EGFR-T790M mutation were enrolled at five institutions in Japan. Among several parameters tested, the progression-free survival (PFS) associated with the initial EGFR-TKIs was positively correlated with the PFS after osimertinib treatment (p = 0.021). The median PFS following osimertinib treatment and the overall survival (OS) were longer in patients who responded to osimertinib than in those who did not (17.7 months versus 3.5 months, p = 0.009 and 24.2 months versus 13.5 months, p = 0.021, respectively). A multivariate analysis demonstrated that the PFS with initial EGFR-TKIs was significantly related to the PFS with osimertinib treatment (p = 0.035), whereas osimertinib response was significantly related to the PFS and OS with osimertinib treatment (p = 0.016 and p = 0.006, respectively). Our retrospective observations indicate that PFS following the initial EGFR-TKI treatment and the response rate to osimertinib might be promising predictors for effective osimertinib treatment in NSCLC patients with the EGFR-T790M mutation.

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Association of plasma EGFR T790M ctDNA status with clinical outcome in advanced NSCLC patients with acquired EGFR-TKI resistance.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.8080 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. 8080-8080

Author(s):

Di Zheng ◽

Xin Ye ◽

Meizhuo Zhang ◽

Yun Sun ◽

Jiying Wang ◽

...

Keyword(s):

Clinical Outcome ◽

Advanced Nsclc ◽

Tki Resistance ◽

Nsclc Patients ◽

Egfr Tki ◽

Egfr T790m

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A digital PCR assay development to detect EGFR T790M mutation in NSCLC patients

Frontiers in Laboratory Medicine ◽

10.1016/j.flm.2018.08.002 ◽

2018 ◽

Vol 2 (3) ◽

pp. 89-96 ◽

Cited By ~ 2

Author(s):

Ruifeng Zhou ◽

Yiran Cai ◽

Zhaoliang Li ◽

Shuangye Shen ◽

Mozhou Sha ◽

...

Keyword(s):

Digital Pcr ◽

Assay Development ◽

Pcr Assay ◽

T790m Mutation ◽

Nsclc Patients ◽

Egfr T790m

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The ability of avitinib to penetrate the blood brain barrier and its control of intra-/extra- cranial disease in patients of non-small cell lung cancer (NSCLC) harboring EGFR T790M mutation.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20613 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20613-e20613 ◽

Cited By ~ 4

Author(s):

Hanping Wang ◽

Li Zhang ◽

Xin Zheng ◽

Xiaotong Zhang ◽

Xiaoyan Si ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Blood Brain Barrier ◽

Cell Lung Cancer ◽

Penetration Rate ◽

Small Cell ◽

Small Cell Lung ◽

T790m Mutation ◽

Nsclc Patients ◽

Egfr T790m

e20613 Background: Avitinib is an oral, potent, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor selective for T790M resistance mutations. We report the safety, the intracranial/extracranial efficacy, and the blood brain barrier (BBB) penetration rate of Avitinib in non-small cell lung cancer(NSCLC) patients with EGFR T790m mutation. The data come from Peking Union Medical College hospital-a single center of the Phase I, open-label, multicenter study (NCT02330367). Methods: NSCLC Patients with acquired EGFR T790m (+) were enrolled. Patients were orally administered with dose escalating from 150 mg to 300 mg twice daily for 28-continuous-day cycles until disease progression. Blood (2mL) and cerebrospinal fluid (CSF) samples (2ml) were collected for concentration analysis on day 29 in available patients with brain metastases (BM). Tumor response was assessed on day 29 and then every 8 weeks. Results: Sixteen patients were included. Nine patients had asymptomatic BM. The most frequent adverse events were the elevated hepatic transaminases (10/16, 62.5%) and diarrhea (5/16, 31.3%), Most were mild and reversible. 9 Patients (56.3%) achieved Partial Response (PR), 6 (37.5%) achieved Stable Disease (SD). Median Progress Free Survival (PFS) was 253 days (95%CI: 154.8-339.2). Of the 8 evaluable BM patients, intracranial PFS were shorter than extracranial in only two patients. The blood and CSF analysis of 6 BM patients showed the BBB penetration rate were 0.046%-0.146% (Table). Conclusions: Avitinib is well tolerated and efficacious in EGFR T790m(+) NSCLC patients. Its concentration in CSF is low, and the penetrability of BBB is weak. But it still showed a good control of BM. Further studies are proceeding. Clinical trial information: NCT02330367. [Table: see text]

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