Gene mutational profiling of Chinese EGFR-T790M mutation NSCLC patients required resistance to osimertinib by next generation sequencing

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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Next-generation sequencing results of brain metastasis in NSCLC patients with acquired EGFR-TKI resistance other than T790M mutation

European Journal of Cancer ◽

10.1016/s0959-8049(16)32815-5 ◽

2016 ◽

Vol 69 ◽

pp. S74-S75

Author(s):

H.Y. Lee ◽

J.H. Kang ◽

J.O. Kim

Keyword(s):

Next Generation Sequencing ◽

Brain Metastasis ◽

Next Generation ◽

T790m Mutation ◽

Tki Resistance ◽

Nsclc Patients ◽

Egfr Tki ◽

Generation Sequencing

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P05.12 Comparison of next-generation sequencing results between brain metastasis and blood in NSCLC patients with acquired EGFR-TKI resistance other than T790M mutation

Neuro-Oncology ◽

10.1093/neuonc/noy139.338 ◽

2018 ◽

Vol 20 (suppl_3) ◽

pp. iii304-iii305

Author(s):

H Lee ◽

J Kim ◽

J Kang

Keyword(s):

Next Generation Sequencing ◽

Brain Metastasis ◽

Next Generation ◽

T790m Mutation ◽

Tki Resistance ◽

Nsclc Patients ◽

Egfr Tki ◽

Generation Sequencing

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Abstract A131: Comparison of next-generation sequencing results between brain metastasis and blood in NSCLC patients with acquired EGFR-TKI resistance other than T790M mutation

10.1158/1535-7163.targ-17-a131 ◽

2018 ◽

Author(s):

Hee Yeon Lee ◽

Jeong-Oh Kim ◽

Jin-Hyoung Kang

Keyword(s):

Next Generation Sequencing ◽

Brain Metastasis ◽

Next Generation ◽

T790m Mutation ◽

Tki Resistance ◽

Nsclc Patients ◽

Egfr Tki ◽

Generation Sequencing

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MA08.01 A Highly Sensitive Next-Generation Sequencing Platform for Detection of NSCLC EGFR T790M Mutation in Urine and Plasma

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2016.11.434 ◽

2017 ◽

Vol 12 (1) ◽

pp. S384-S385 ◽

Cited By ~ 5

Author(s):

Heather Wakelee ◽

Vlada Melnikova ◽

Chris Karlovich ◽

Shirish Gadgeel ◽

Karen Reckamp ◽

...

Keyword(s):

Next Generation Sequencing ◽

Next Generation ◽

T790m Mutation ◽

Sequencing Platform ◽

Next Generation Sequencing Platform ◽

Highly Sensitive ◽

Generation Sequencing ◽

Egfr T790m

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Mutational Profiling of Non-Small-Cell Lung Cancer Resistant to Osimertinib Using Next-Generation Sequencing in Chinese Patients

BioMed Research International ◽

10.1155/2018/9010353 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 7

Author(s):

Keke Nie ◽

Haiping Jiang ◽

Chunling Zhang ◽

Chuanxin Geng ◽

Xiajuan Xu ◽

...

Keyword(s):

Next Generation Sequencing ◽

Needle Biopsy ◽

Small Cell ◽

Chinese Patients ◽

Next Generation ◽

Small Cell Lung ◽

T790m Mutation ◽

Core Needle ◽

Generation Sequencing ◽

Egfr T790m

Purpose. To identify the somatic mutated genes for optimal targets of non-small-cell lung cancer after resistance to osimertinib treatment. Patients and Methods. Study patients all had advanced lung adenocarcinoma and acquired resistance to osimertinib as a second- or third-line treatment. These patients had harboring EGFR T790M mutation before osimertinib treatment, which was confirmed by Amplification Refractory Mutation System (ARMS) PCR or Next-Generation Sequencing (NGS). After resistance to osimertinib treatment, tumor tissue was collected by core needle biopsy. DNA was extracted from 15 × 5 um sliced section of formalin-fixed paraffin-embedded (FFPE) material and NGS was done. The genetic changes were analyzed. Results. A total of 9 Chinese patients were studied, 5 females and 4 males, age 51–89 years. After progression with osimertinib treatment, core needle biopsy was performed and next-generation sequencing was performed. Nine patients had harboring 62 point mutations, 2 altered gene copies, 2 amplifications, and 1 EML4-ALK gene fusion. No MET or HER2 amplification was found in this cohort study. Nine patients still maintained initial EGFR 19 del or L858R activating mutations, while 7 of them kept EGFR T790M mutations. Among the 7 patients, 5 had secondary EGFR C797S and/or C797G mutations, which all happened in the same allele with T790M mutation. All patients were treated with targets therapies, chemotherapy, or best supportive care (BSC) in accordance with NGS genetic results and patients’ performance status; 7 of them are still alive and 2 of them died of disease progression at last follow-up. Conclusions. EGFR C797S/G mutation and the same one presented on the same allele with EGFR T790M mutation were the most common mutation feature and played a key role in resistance to osimertinib in Chinese patients with NSCLC. Tumor cells losing T790M mutation and maintaining EGFR activating mutation might benefit from first-generation EGFR-TKI treatment.

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