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Attend this session at the
2019 ASCO Annual Meeting!


Session: Lung Cancer—Non-Small Cell Metastatic

Type: Poster Session

Time: Sunday June 2, 8:00 AM to 11:00 AM

Location: Hall A

Acquired resistance to MET inhibition in MET driven NSCLC.

Sub-category:
Metastatic Non-Small Cell Lung Cancer

Category:
Lung Cancer—Non-Small Cell Metastatic

Meeting:
2019 ASCO Annual Meeting

Abstract No:
9030

Poster Board Number:
Poster Session (Board #353)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 9030)

Author(s): Richard Riedel, Carina Heydt, Andreas H. Scheel, Hannah Lea Tumbrink, Johannes Brägelmann, Roberta Castiglione, Lucia Nogova, Diana S.Y. Abdulla, Sebastian Yves Friedrich Michels, Matthias Scheffler, Rieke Nila Fischer, Sophia Koleczko, Sabine Merkelbach-Bruse, Martin Sos, Reinhard Büttner, Juergen Wolf; Lung Cancer Group Cologne, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Dept. for Internal Medicine, Cologne, Germany; Lung Cancer Group Cologne, Institute of Pathology, University Hospital of Cologne, Cologne, Germany; Institute of Pathology, University Hospital of Cologne, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Pathology, Cologne, Germany; University of Cologne, Cologne, Germany; Lung Cancer Group Cologne, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Dept. I of Internal Medicine, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital of Cologne, Institute for Pathology, Cologne, Germany; University Hospital Cologne, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, Cologne, Germany

Abstract Disclosures

Abstract:

Background: MET mutations (METex14), amplifications or translocations can activate oncogenic signaling in lung cancer and are sensitive to MET inhibition. Acquired resistance to therapy with MET tyrosine kinase inhibitors (TKI) occurs inevitably. Methods: Between 2015 and 2018, eighteen patients with MET-driven NSCLC were treated with capmatinib or crizotinib as single agent at our site. Rebiopsy samples from five patients were analyzed by NGS and fluoreszenz-in-situ hybridization (FISH) at time of progression. Results: Of the five patients with rebiopsy samples at time of progression, two had initially a MET amplification (one patient with low-level and one patient with high-level amplification), two patients had a METex14 and one patient had a KIF5B-MET fusion. Patient 1 (low-level MET amplification) showed a partial response to crizotinib. The rebiopsy revealed an acquired KRAS mutation as a potential mechanism of resistance. Patient 2 (high-level MET amplification) showed stable disease as best response to capmatinib and patient 3 (MET∆ex14) showed a partial response to capmatinib. Both patients developed acquired HER2 amplifications. Patient 4 (METex14) showed initially a partial response to crizotinib. The rebiopsy sample revealed an acquired MET kinase domain mutation (p.D1246N). As preclinical findings suggested that D1246N confers resistance to type I MET inhibitors but remains sensitive to type II inhibitors, cabozantinib was started. A CT six weeks after therapy initiation showed progressive disease. Patient 5 (KIF5B-MET) had a partial response to crizotinib. An acquired MET p.Y1248H mutation was found at time of progression. Therapy was changed to cabozantinib. A new CT scan is pending. Conclusions: Resistance to MET inhibition is heterogeneous with on- and off-target-mechanisms occurring. We found HER2 amplification as a potential new bypass mechanism. The MET mutation D1246N conferred resistance to type I and type II inhibitors. We describe the first case of an acquired mutation of the MET tyrosine kinase domain in a patient with an oncogenic MET fusion. Further investigations are needed to collect comprehensive data to understand resistance mechanisms in MET inhibition and to develop novel therapeutic strategies.

 
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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