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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.

MET second-site mutations in EGFR-mutant, MET-amplified non-small cell lung cancer after resistance to combinatorial targeted therapy.

Sub-category:
Metastatic Non-Small Cell Lung Cancer

Category:
Lung Cancer—Non-Small Cell Metastatic

Meeting:
2019 ASCO Annual Meeting

Abstract No:
e20730

Citation:
J Clin Oncol 37, 2019 (suppl; abstr e20730)

Author(s): Jia-Tao Cheng, Jinji Yang, Yilong Wu; Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China; Division of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, P. R. China, Guangdong, China; Guangdong Provincial People's Hospital, Guangzhou, China

Abstract Disclosures

Abstract:

Background: MET second-site mutations were previously reported in a few cases of MET-amplified or exon 14-mutant advanced non-small-cell lung cancer (NSCLC) treated with MET inhibitors. However, both the frequency of MET second-site mutations and clinical outcome of patients with such genetic alterations have not been investigated, particularly in EGFR-mutant, MET-amplified advanced NSCLC treated with combinatorial targeted therapy. Methods: Retrospectively, from November 2016 to January 2019, 22 patients with EGFR-mutant, MET-amplified advanced NSCLC had sufficient tumor samples after resistance to a combinatorial therapy with both EGFR and MET inhibitors. All tissue samples were detected using Next-generation sequencing (NGS). The progression-free survival (PFS) was calculated the start of subsequent treatment to progressive disease or death from any cause. The overall survival (OS) was calculated from the start of subsequent treatment to death from any cause. Last follow-up was on January 31, 2019. Results: Five kinds of MET second-site mutations were found in 7 patients: D1246N D1228N, D1228H, D1231Y and Y1230H. The frequency of MET second-site mutations was 31.8% (7/22). The median PFS and OS were 3.7 (95%CI: 1.13-6.3) months and 6.9 (95%CI: 0.2-13.7) months respectively. The ORR of EGFR TKIs plus cabozantinib for suchsecond-site mutaant patients was 50% (2/4). However, the ORR of other treatments was 0% (0/3), Two of them received single agent cabozantinib, and PFS was 0.7 and 1.7 months respectively. One had a PFS of 2.5 months with pemetrexed/carboplatin plus bevacizumab. Conclusions:MET second-site mutation might be one of the commonly-seen molecular mechanisms of acquired resistance to combinatorial targeted therapy in EGFR-mutant, MET-amplified advanced NSCLC. Patients with such mutations could respond to cabozantinib plus EGFR TKI. Further more investigations are warranted to improve the efficacy.

 
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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