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Egbert F Smit
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MA19 - Genomic Markers of IO Response (ID 922)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 15:15 - 16:45, Room 201 BD
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MA19.08 - Detection of Primary Immunotherapy Resistance to PD-1 Checkpoint Inhibitors (PD1CI) in 2nd Line NSCLC (ID 13916)
16:05 - 16:10 | Author(s): Egbert F Smit
- Abstract
- Presentation
Background
PD1CI are capable of restoring immunity, but some patients do not benefit. While molecular tests like PD-L1 expression and TMB help in enriching response in respective subsets, a test identifying patients showing primary resistance to PD1CI which does not require tissue samples could help in optimizing treatment regimens.
a9ded1e5ce5d75814730bb4caaf49419 Method
Sophisticated mass spectrometry profiling data from a development set (S) of pre-treatment serum from 116 2nd line NSCLC patients treated with nivolumab were correlated with outcome data (PFS/OS)using multivariate machine learning techniques related to deep learning. The resulting test stratified patients into three groups: group A having very poor outcomes, group B having intermediate outcomes, and group C having very good outcomes. Development results were obtained using out-of-bag estimators. Two additional patient cohorts treated with nivolumab, V1(N=58) and V2(N=75), were used for validation.
4c3880bb027f159e801041b1021e88e8 Result
The proportions of patients in A, B, and C were 41:43:32 in S, 23:18:17 in V1, and 32:19:24 in V2. Median PFS/OS in the poor prognosis group A was 43/132 days in S, 105/189 days in V1, 90/278 days in V2, and in the good prognosis group C 276/528 days in S, 192/459 days in V1, and 155/not reached days in V2. In a comparison with historical controls treated with single agent chemotherapy and analyzed with the same technique, nivolumab appeared substantially superior in the good prognosis group C, while there was no evidence of superiority in the poor prognosis group A. In multivariate analysis including performance status, smoking history, and histology, the test remained an independent predictor of outcome. The patterns of protein expression related to poor prognosis in group A patients were associated with elevated complement, wound healing, and acute phase reactants.
8eea62084ca7e541d918e823422bd82e Conclusion
We developed and validated a test stratifying patients into three groups with significantly different outcomes on nivolumab. The poor prognosis group showed little benefit from nivolumab, and other treatments may be needed, while in the good prognosis group outcomes were very good for a 2nd line population. Our results emphasize the important role of the host immune response in the prediction of PD1CI efficacy. Data on PD-L1 IHC from these cohorts will be included in the multivariate analysis and presented at the meeting.
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MA25 - Oligometastasis: Defining, Treating, and Evaluating (ID 929)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 203 BD
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MA25.02 - Searching for a Definition of Synchronous Oligometastatic (sOMD)-NSCLC: A Consensus from Thoracic Oncology Experts (ID 13452)
13:40 - 13:45 | Author(s): Egbert F Smit
- Abstract
- Presentation
Background
Recent prospective single centre studies reported improved outcomes in patients with sOMD-NSCLC who were treated with radical intent. Since then sOMD has been perceived as a separate disease entity. However, a clear definition of sOMD-NSCLC is lacking. We aimed to develop a definition and diagnostic criteria of sOMD-NSCLC following a consensus process.
a9ded1e5ce5d75814730bb4caaf49419 Method
A European multidisciplinary consensus group was established with representatives from different scientific societies. Consensus questions were extracted from a survey, case series and a systematic review. The questions were discussed, and the statement formulated during a consensus meeting in Dublin (23.01.18).
4c3880bb027f159e801041b1021e88e8 Result
Summary of consensus statement
Defining sOMD-NSCLC
Definition of sOMD is relevant for patients in whom a radical treatment is technically feasible with acceptable toxicity, taking into account all sites, that may modify the course of the disease leading to a long-term disease control.
All sites must be technically and safely treatable.
The maximum number of metastases/organs meeting the criteria involved will depend on the possibility of offering a treatment strategy with radical intent, taking into account local control and toxicity. Based on the systematic review, a maximum of 5 metastases and 3 organs is proposed.
Diffuse serosal metastases and bone marrow involvement are excluded.
Mediastinal lymph node (MLN) involvement should be considered as locoregional disease in the definition of sOMD-NSCLC.
MLN involvement is of importance in determining if a radical local treatment of the primary tumour may be applied and the MLN will not be counted as a metastatic site.
Staging of sOMD-NSCLC
PET-CT and brain imaging are considered mandatory.
In case of a solitary liver metastasis a dedicated MRI of the liver and for a solitary pleural metastasis, thoracoscopy and biopsies of distant ipsilateral pleural sites are advised.
Staging of the mediastinum requires a minimum of a FDG-PET scan, with pathological confirmation preferred if this influences the treatment strategy.
Pathological proof is required unless the MDT decides that the risk outweighs the benefit. Pathology proof is advised for single metastatic location and if it may change the therapeutic strategy, confirmation of the MLN involvement is recommended.
8eea62084ca7e541d918e823422bd82e Conclusion
A multidisciplinary consensus statement on the definition and staging of sOMD-NSCLC was formulated taking into account results of a European survey, a systematic review and case discussion. This statement might be helpful to standardise inclusion criteria in future clinical trials. However, the definition of sOMD may change over time when more prospective data will become available.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MA26 - New Therapies and Emerging Data in ALK, EGFR and ROS1 (ID 930)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 201 BD
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MA26.06 - Crizotinib-Treated ALK Immunopositive Metastasized NSCLC is Associated with an Unfavorable Prognosis when FISH Negative (ID 13179)
14:05 - 14:10 | Author(s): Egbert F Smit
- Abstract
- Presentation
Background
Metastasized NSCLC with an ALK fusion are sensitive to a range of tyrosine kinase inhibitors. ALK-positive NSCLC has been identified in the pivotal phase III trial with fluorescence in situ hybridization (ALK FISH+). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC)+). However, discrepant cases occur, including ALK IHC+ FISH-. The aim of this study was to collect ALK IHC+ cases and compare within this group response to crizotinib treatment of ALK FISH+ cases with ALK FISH- cases.
a9ded1e5ce5d75814730bb4caaf49419 Method
A prospective multicenter investigator initiated research study was started in Europe. Stage IV ALK IHC+ NSCLC cases treated with crizotinib were collected centrally. Slides were validated centrally for ALK IHC (with 5A4 ETOP and D5F3 Ventana protocol) and ALK FISH (Vysis probes).
4c3880bb027f159e801041b1021e88e8 Result
The study started April 1, 2014 and closed in November 2017. Fifteen centers participated. Registration of 3523 ALK IHC tests revealed prevalence of 2.6% ALK IHC+ cases. Local ALK FISH analysis resulted in 46 concordant (ALK IHC+/FISH+) and 18 discordant (ALK IHC+/FISH-) cases. Central validation revealed 37 concordant and 6 discordant cases, 5 of which had follow-up. Validation was hampered by limited amount of tissue in biopsy samples. The time to treatment failure did not differ for concordant nor discordant cases, and neither for local nor validated ALK testing (HR=0.78; 95% CI= 0.27-2.3; p=0.64) and (HR=2.2; 95% CI= 0.72-6.5; p=0.16), respectively). However, overall survival was significantly better for concordant cases than discordant cases after central validation (HR=4.5; 95% CI= 1.2-15.9; p=0.010), but not according to local testing (HR=1.7; 95% CI= 0.45-6.2; p=0.44).
8eea62084ca7e541d918e823422bd82e Conclusion
ALK IHC+ FISH- NSCLC cases are an infrequent finding. We recommend such cases to be validated carefully because our data indicate that ALK IHC+ FISH- cases have a worse survival when treated by crizotinib compared to ALK IHC+ FISH+ cases.
This study was funded by an independent research grant by Pfizer
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.13-42 - Osimertinib Treatment for Patients with EGFR exon 20 Insertion Positive Non-Small-Cell Lung Cancer (ID 14152)
16:45 - 18:00 | Author(s): Egbert F Smit
- Abstract
Background
Epidermal growth factor receptor (EGFR) exon 20 insertions are identified in 4-10% of al EGFR mutations in non-small cell lung cancer (NSCLC) and are generally associated with primary resistance to first and second generation EGFR tyrosine kinase inhibitors (TKIs). In vitro and preclinical animal studies have shown that osimertinib exerts antitumor activity in EGFR exon 20 insertion positive NSCLC cell lines. We report on a cohort of advanced stage NSCLC patients, harboring an EGFR exon 20 insertion, that was treated with osimertinib.
a9ded1e5ce5d75814730bb4caaf49419 Method
17 patients with advanced NSCLC harboring an EGFR exon 20 insertion were treated with osimertinib 80 mg once daily, in four institutions in the Netherlands. Data were obtained retrospectively. EGFR mutation status was assessed by next-generation sequencing. Progression free survival (PFS), disease control rate (DCR) and objective response rate (ORR) were assessed using RECIST v1.1.
4c3880bb027f159e801041b1021e88e8 Result
Median age was 63 years (range 35 – 81), 71% was female and median number of prior systemic treatments was 1 (range 0 – 3). Ten patients (59%) received prior platinum-based chemotherapy, and 2 patients afatinib, one patient experienced stable disease for 11 months, the other patient showed progression. Among all patients treated with osimertinib, we observed 1 partial response, 13 patients with stable diseases and 3 with progressive disease as best response (ORR 6%). Two patients were still on osimertinib treatment at the cut-off date. Median PFS was 3.7 months (95% CI: 2.3 – 5.4 months). Six of seventeen patients (35%) achieved DCR at five months.
Patient
Number of prior treatments
Prior platinum based chemotherapy
Prior EGFR TKI
Best RECIST response
PFS (months)
1
2
Yes
no
SD
4.0
2
1
Yes
no
SD
1.6
3
2
Yes
no
PR
0.7
4
1
Yes
no
PR
0.7
5
2
Yes
no
SD
3.8
6
1
Yes
no
SD
3.0
7
3
Yes
no
SD
9.3
8
1
Yes
no
SD
17.0
9
1
No
no
SD
3.7
10
1
Yes
no
SD
17.2
11
0
No
no
PR
3.1
12
0
No
no
SD
2.6
13
0
No
no
SD
6.5
14
3
Yes
afatinib (SD)
SD
7.9
15
1
No
afatinib (PD)
PD
1.7
16
0
no
no
SD
8.3
17
0
no
no
SD
1.4
EGFR, epidermal growth factor receptor; RECIST: Response Evaluation Criteria in Solid Tumors; PR, partial response; SD, stable disease; PD, progressive disease; PFS, progression free survival
8eea62084ca7e541d918e823422bd82e Conclusion
Osimertinib has limited antitumor activity in patients with EGFR exon 20 mutated NSCLC, with an ORR of 6%. A subset of patients (35%) seems to derive benefit from osimertinib treatment with durable disease control for more than five months.
6f8b794f3246b0c1e1780bb4d4d5dc53
