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O. Burghuber
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ED06 - Symptom Management in Lung Cancer (ID 269)
- Event: WCLC 2016
- Type: Education Session
- Track: Palliative Care/Ethics
- Presentations: 1
- Moderators:R. Gralla, R. Malayeri
- Coordinates: 12/05/2016, 16:00 - 17:30, Stolz 1
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ED06.01 - Causes and Management of Dyspnea (ID 6447)
16:00 - 16:15 | Author(s): O. Burghuber
- Abstract
- Presentation
Abstract not provided
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P1.04 - Poster Session with Presenters Present (ID 456)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Pulmonology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.04-001 - EGFR, EML4-ALK, ROS 1 and BRAF Testing in Austrian Patients with NSCLC: A Multicentre Study (ID 4449)
14:30 - 14:30 | Author(s): O. Burghuber
- Abstract
Background:
Targeted therapy is becoming increasingly important and has improved the overall survival for patients with NSCLC. EGFR and BRAF mutations, EML4-ALK and ROS1 translocations are current allocatable targets. The incidence of these druggable targets in Austria is unknown.
Methods:
Tumor tissue from bronchoscopy, CT- and ultrasound guided biopsies as well as surgical specimen with histological type of adenocarcinoma and NSCLC NOS (Not Otherwise Specified) were routinely analyzed independent of the tumor stage and clinical characteristics (reflex testing) for these genetic alterations. Since January 2010 the EGFR mutation detection was performed with the EGFR Mutation Test Kit from ROCHE on a COBAS4800. Since August 2011 tumor tissue was analyzed for EML4-ALK with a two-step procedure. First an immunohistochemical staining was done with the Ventana anti ALK(D5F3), OptiView DAB IHC DetectionKit and OptiViewAmplifikationKit® and further on positive cases were tested by PCR (AmoyDx®EML4-ALK FusionGeneDetectionKit) or ALK FISH (dual colour breakapart FISH/Abbott Vysis®). Since January 2014 the tumor tissue was analyzed for ROS1 with a two-step procedure. First an immunohistochemical staining was done with ROS1 D4D6, cell signaling® and further on positive cases were tested by PCR (AmoyDx®ROS1 GeneFusionDetectionKit) or ROS1 FISH (ROS1-6q22.1 dual colour breakapart probe ZytoVision®). BRAF testing was performed with the cobas®4800BRAF V600Mutation Test from Roche since March 2016.
Results:
An EGFR Mutation was found in 340 out of 2776 patients (12.2%). 253 patients (9.1%) carried an activated mutation (Exon 19 Deletion, Exon 21 L858R). EML4-ALK positive translocation was found in 100 out of 2212 patients (4.5%). ROS1 positive translocation was found in 5 out of 1060 patients (0.5%). BRAF mutation was found in 3 patients out of 40 (7.5%).
Conclusion:
Frequency of these genetic alterations in Austrian patients with NSCLC was quite similar to other Caucasian peers. Therefore reflex testing is recommended independent of any clinical characterization.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-032 - Association between EGFR T790M Mutation Copy Numbers in Cell-Free Plasma DNA and Response to Osimertinib in Advanced NSCLC (ID 5454)
14:30 - 14:30 | Author(s): O. Burghuber
- Abstract
Background:
Patients with advanced EGFR-mutated non-small-cell lung cancer (NSCLC) who developed the T790M resistance mutation during treatment with EGFR tyrosine kinase inhibitors (TKIs) benefit from treatment with third-generation EGFR TKIs such as osimertinib. Treatment with osimertinib requires the confirmation of the presence of the T790M mutation by re-biopsy of the tumor or by analysis of cell-free plasma DNA from blood samples (liquid biopsy). The purpose of our study was to compare T790M mutation copy numbers in cell-free plasma DNA with response to osimertinib.
Methods:
From April 2015 to June 2016, we included 44 patients with advanced T790M-positive NSCLC who received osimertinib after previous disease progression with an EFGR TKI and in whom response to osimertinib was evaluable. T790M mutation status was assessed by droplet digital PCR in cell-free plasma DNA. The threshold for T790M positivity was >1 copy/mL.
Results:
The T790M mutation status was assessed in all patients by liquid biopsy and in 18 patients also by re-biopsy of the tumor. All 44 patients were T790M-positive in the liquid biopsy. Two out of 18 (11%) patients had a T790M-negative re-biopsy. Thirty-seven patients (86%) showed a response to treatment with osimertinib: 13 (29.5%) complete responses (CR), 24 (54.5%) partial responses (PR), one (2%) stable disease (SD), and six (14%) progressive disease (PD) (Table 1). We observed no statistically significant association between response to osimertinib and T790M copy numbers (p=0.54; Table 1). The median T790M copy numbers across response categories were: CR 25 copies/mL (range 1.7-38092 copies/mL), PR 14 copies/mL (range 1.6-7282 copies/mL), SD+PD 6 copies/mL (range 1.8-475 copies/mL).Table 1 Response Copies/mL CR PR SD PD <10 5 (39%) 11 (46%) 0 (0%) 4 (67%) ≥10 8 (62%) 13 (54%) 1 (100%) 2 (33%)
Conclusion:
Patients benefited from osimertinib treatment independent of T790M copy numbers in the blood samples. Although limited by low numbers, we observed a trend towards better response to osimertinib in patients with ≥10 T790M copies/mL.
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P3.02b-101 - EGFR T790M Resistance Mutation in NSCLC: Real-Life Data of Austrian Patients Treated with Osimertinib (ID 4225)
14:30 - 14:30 | Author(s): O. Burghuber
- Abstract
Background:
Somatic mutations in the epidermal growth factor receptor (EGFR) are detected in approximately 13% of the Austrian non-small cell lung cancer (NSCLC) patients. The EGFR T790M resistance mutation located on Exon 20 is the most common mechanism of drug resistance to EGFR tyrosine kinase inhibitors (TKI) in these patients. The mutation can be detected by re-biopsy as well liquid biopsy. Osimertinib (AZD9291), a 3[rd] generation EGFR-TKI, showed a highly clinical activity in these patients. We report about our experience with Osimertinib in EGFR-mutated NSCLC patients, who became resistant to first or second generation TKI`s due to EGFR T790M mutation.
Methods:
From April 2015 to June 2016 we administered osimertinib 80 mg daily to 82 patients who had disease progression after previous treatment with an EFGR TKI. The T790M mutation status was assessed by re-biopsy and/or liquid biopsy. For liquid biopsies, blood samples were collected in EDTA-containing vacutainer tubes and processed within 2 hours after collection. Cell-free plasma DNA was extracted by using the QIAamp circulating nucleic acid kit (Qiagen) according to the manufacturer’s instructions. Mutation status was assessed with QX-100™ Droplet Digital™ PCR System (Bio-Rad).
Results:
The T790M mutation status was assessed in 48 patients by liquid biopsy only and in 13 patients by re-biopsy of the tumor. In 21 patients the T790M mutation was detected by both methods. 70 (85%) patients showed a clear clinical and radiographic response. Out of these, 70 patients, 14 (17%) patients reached a complete remission, 56 (68%) patients showed partial response and in 5 (6%) patients, a stable disease after treatment with osimertinib was observed. Five patients had symptomatic brain metastasis initaly without any further option of local treatment, and showed a clear a clear clinical benefit and a partial remission radiographically. Osimertinib was well tolerated. No clinically relevant significant side effects were reported.
Conclusion:
Osimertinib was highly active in our patients, while showing good safety profile. Therefore, re-biopsy or liquid biopsy should be performed in clinical routine to detect the T790M mutation. With the above described method, liquid biopsy could replace re-biopsy in clinical practice in the future.
