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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.

Overcoming acquired osimertinib-resistance in EGFR-mutant advanced non-small lung cancer mediated by activating BRAF V600E mutation.

Sub-category:
Metastatic Non-Small Cell Lung Cancer

Category:
Lung Cancer—Non-Small Cell Metastatic

Meeting:
2019 ASCO Annual Meeting

Abstract No:
e20682

Citation:
J Clin Oncol 37, 2019 (suppl; abstr e20682)

Author(s): Diana S.Y. Abdulla, Matthias Scheffler, Carsten Kobe, Thorsten Persigehl, Matthias Schmidt, Jana Fassunke, Sabine Merkelbach-Bruse, Sebastian Yves Friedrich Michels, Lucia Nogova, Sophia Koleczko, Rieke Nila Fischer, Richard Riedel, Alexander Drzezga, Reinhard Büttner, Juergen Wolf; 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, Dept. of Nuclear Medicine, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital of Cologne, Dept. of Radiology, Köln, Germany; University of Cologne, Faculty of Medicine and University Hospital of Cologne, Institute for Pathology, Cologne, Germany; Lung Cancer Group Cologne, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Dept. for Internal Medicine, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital of Cologne, Department of Nuclear medicine, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, Cologne, Germany

Abstract Disclosures

Abstract:

Background: There is growing insight in the mechanisms underlying resistance to the 3rdgeneration EGFR inhibitor osimertinib. Unlike resistance to 1stgeneration inhibitors, these mechanisms not necessarily lead to sequential targeted therapy approaches. Here we report on the treatment of two patients with acquired resistance to osimertinib with a new detected BRAF V600E mutation as resistance mechanism. Methods: We identified two patients with EGFR-T790M-mutant advanced NSCLC with progression on osimertinib and detection of a new BRAFV600E mutation in a tumor rebiopsy by next-generation sequencing (NGS). No other known resistance mechanism beside T790M loss in one patient was found. Osimertinib was discontinued and BRAF-targeted combination therapy with dabrafenib and trametinib at standard dose was initiated. We monitored the clinical course with sequential 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) / computed tomography (CT) assessing maximum standard uptake value (SUVmax), sequencing based liquid biopsies and tumor marker assessment. Results: Patient (1) with EGFR del19 (E746_A750del), preserved T790M mutation and acquired BRAF V600E mutation showed reduction in FDG uptake of 18% after 2 weeks of dabrafenib/trametinib that demonstrated a slight increase of 12% in a FDG-PET/CT scan 4 weeks thereafter and combination treatment has been continued. Patient (2) with EGFR del19 (E746_A750del), T790M loss and new BRAF V600E mutation showed continuous metabolic (+8% and + 39%, respectively) and morphologic progression after 2 and 4 weeks of dabrafenib and trametinib. A tumor rebiopsy showed no additional molecular changes. We changed the treatment to osimertinib and dabrafenib combination and observed an impressive metabolic response (-33%) after 2 weeks by FDG-PET/CT. Conclusions:BRAF V600E mutation has recently been described as a novel molecular resistance mechanism in osimertinib-resistant EGFR-mutant NSCLC. We describe one patient where combined BRAF/MEK inhibition with no additional EGFR-inhibition resulted in a preliminary feasible tumor control, but confirmatory CT staging is pending. In a second patient, co-inhibition of EGFR and BRAF pathway with osimertinib and dabrafenib was needed to overcome BRAF-mediated osimertinib resistance resulting in an impressive early tumor response that was not observed to either single-target inhibition of EGFR or BRAF. FDG-PET/CT was able to monitor tumor dynamics. Updated data will be presented.

 
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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