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Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.

RET fusion in first/third-generation EGFR-TKIs resistance in advanced non-small cell lung cancer.

Sub-category:
Metastatic Non-Small Cell Lung Cancer

Category:
Lung Cancer—Non-Small Cell Metastatic

Meeting:
2019 ASCO Annual Meeting

Abstract No:
e20634

Citation:
J Clin Oncol 37, 2019 (suppl; abstr e20634)

Author(s): Yu Yao, Min Zhang, Xiuju Liu, Jun Zhao, Xiangyang Cheng, Aiping Zeng, Jinliang Kong, Hongliang Zhang, Rongrong Chen, Xuefeng Xia; Department of medical Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi‘’an, China; Geneplus-Beijing Institute, Beijing, China; Shandong Cancer Hospital, Jinan, China; Beijing University School of Oncology Beijing Institute for Cancer Research, Beijing, China; The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; GuangXi Tumour Hospital, Nanning, China; The First Affiliated Hospital of Guangxi Medical University, Nanning, China; Traditional Chinese Medicine Hospital of Xinjiang Uyghur Autonomous Region, Second Department of Oncology, Urumchi, China; Houston Methodist Research Institute, Weill Cornell School of Medicine, Houston, TX

Abstract Disclosures

Abstract:

Background: EGFR-TKIs is the standard first/second-line treatment for EGFR-mutant advanced non-small-cell lung cancer (NSCLC). The mechanisms of EGFR-TKIs resistance are still under exploration. Acquired fusion have been reported contribute to EGFR-TKIs resistance. Here we focus on RET fusion in first/third-generation EGFR-TKIs resistant NSCLC. Methods: We retrospectively reviewed 3600 cases of EGFR-TKIs resistant NSCLC samples from 2016 to 2018 in our institute. Tumor biopsy, ctDNA or pleural effusion samples were analyzed using hybridization capture-based NGS ER-seq method, which enables simultaneously assess single-nucleotide variants (SNV), insertions/deletions (indel), rearrangements and somatic copy-number(CNV) variation at least 59 genes (range 59-1021 genes). Results: Seven cases with RET fusion were identified (7/3600, 0.2%), with co-occurring EGFR mutations. All were adenocarcinoma, median diagnosis age was 55 years old (range 38-84), four male and three female. Most common RET fusion subtype was CCDC6-RET (5/7, 71%), the other was NCOA4-RET (2/7, 29%). The primary EGFR mutation include four EX19del and three L858R. Six patients received prior first and third-generation EGFR-TKIs treatment. The seventh patient had received only gefitinib treatment, EGFR L858R + T790M + NCOA4-RET were discovered in his plasma when disease progression. Interestingly, one patient had EGFR EX19del + T790M + C797S (cis) + CCDC6-RET in plasma after osimertinib resistance. One patient who had EGFR L858R and NCOA4-RET chose lenvatinib, a RET inhibitor, and had a progression free survival of seven months. Conclusions: Broad NGS panel test suggests that RET fusion could be a rare mechanism of EGFR-TKIs resistance, include first and third-generation. There is no currently target treatment strategy available for these patients, and further investigations, like change target therapy drug or combined target therapy are needed.

 
Other Abstracts in this Sub-Category:

 

1. Association of STK11/LKB1 genomic alterations with lack of benefit from the addition of pembrolizumab to platinum doublet chemotherapy in non-squamous non-small cell lung cancer.

Meeting: 2019 ASCO Annual Meeting Abstract No: 102 First Author: Ferdinandos Skoulidis
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

2. Real-world outcomes of patients with advanced non-small cell lung cancer (aNSCLC) and autoimmune disease (AD) receiving immune checkpoint inhibitors (ICIs).

Meeting: 2019 ASCO Annual Meeting Abstract No: 110 First Author: Sean Khozin
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

3. RELAY: A multinational, double-blind, randomized Phase 3 study of erlotinib (ERL) in combination with ramucirumab (RAM) or placebo (PL) in previously untreated patients with epidermal growth factor receptor mutation-positive (EGFRm) metastatic non-small cell lung cancer (NSCLC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 9000 First Author: Kazuhiko Nakagawa
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

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