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Magdalena Knetki-Wróblewska
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P37 - Pathology - Biomarker Testing (ID 107)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P37.02 - Identification of Gene Fusions and Mutations in Patients with NSCLC using two Diagnostic Approaches: Rapid qPCR and NGS (ID 3731)
00:00 - 00:00 | Author(s): Magdalena Knetki-Wróblewska
- Abstract
Introduction
Background
The mutation detection, and especially fusion gene identification in patients with non-small cell lung cancers (NSCLCs), is currently a key step in the diagnosis and treatment decision. Therefore, methods are constantly being developed to be more specific, rapid and provide extensive biomarker analysis. NGS seems to be the most suitable diagnostic approach. However, this method is time-consuming, costly, and requires highly specialized devices and analytical background. Consequently, novel rapid and sensitive tests basing on qPCR emerge.
Aim
The aim of this study was to compare the diagnostic yield of NGS (RNA based sequencing) and qPCR- based Lung Cancer PCR Panel, which identifies 231 variants (gene fusions and point mutations) in 11 genes (ROS, ALK, NTRK1/2/3, RET, MET, KRAS, HER2, BRAF, EGFR) in patients treated in a single cancer center.
Methods
194 solid tumors formalin-fixed paraffin-embedded (FFPE) specimens from NSCLC patients were selected for the study. The samples were primarily analyzed using NGS (Archer, RNA-based anchored multiplex-PCR) where gene fusions or point mutations (single nucleotide substitutions and small insertions/deletions) were detected or negative results were obtained. In a second step samples were analyzed again by using a qPCR panel (AmoyDx, Lung Cancer PCR Panel).
Results
194 samples (66 with gene fusions, 72 with point mutations and 56 negative samples) were analyzed with both methods. The qPCR enabled detection of 45/66 gene fusions (68%). In 21/66 cases fusions were not detected (32%), of which 12 were beyond the scope of the qPCR test. In 9 cases the fusions were not detected due to unknown reason. The qPCR test enabled detection of 74 point mutations. 72 of them were also detected using NGS, while 2 were found in cases previously classified as negative by NGS testing. Finally, 54cases were negative in both tests.
Conclusion
This comparative study showed high concordance (89%) between qPCR and NGS panels. The multigene PCR panels seem to be good alternative to NGS panels and can be seriously considered as screening methods due to their universality, methodological simplicity, cost, and short time of analysis
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P78 - Immunotherapy (Phase II/III Trials) - Immune Checkpoint Inhibitor Single Agent (ID 255)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P78.08 - Prediction of Pembrolizumab Efficacy in Non-Small-Cell Lung Cancer (NSCLC) Based on Experience From Expanded Access Program in Poland (ID 2972)
00:00 - 00:00 | Presenting Author(s): Magdalena Knetki-Wróblewska
- Abstract
Introduction
Efficacy of pembrolizumab in advanced pretreated NSCLC was documented in prospective trials. We aimed to confirm the benefits of pembrolizumab in daily practice.
Methods
This study was a retrospective analysis of patients (pts) treated in the Expanded Access Program in Poland. Median of progression-free (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Analyses were performed with R 3.6.0 software.
Results
A total of 34 pts were qualified to pembrolizumab in second or third line of NSCLC treatment. Poor performance status (ECOG 2) was found in 14.7% of pts, brain and liver metastases were diagnosed in 8.8% and 17.6%, respectively. 38% of pts ended the treatment before radiological assessment mainly due to clinical deterioration. In the landmark of 12 and 24 months 35% and 17.6% pts remained alive.
Median PFS and OS were 4.4 months (95% confidence interval [CI]: 3.4–9.0) and 8.2 months (95% CI: 4.1–16.1). Immune related adverse events (irAE) were reported in 23% of pts. No treatment-related deaths were reported. In an univariate analysis an ECOG PS 2 (p < 0.001), tumor diameter of >100 mm (p = 0.019), PD during previous chemotherapy (p = 0.037), platelet count (PLT) >409 109/L (p = 0.011), a neutrophil-to-lymphocyte ratio (NLR) ≥3.1 (p = 0.0001) and platelet-to-lymphocyte ratio (PLR) of >183 (p = 0.018) had a negative impact on PFS. The age, sex, histology, location of metastases, PD-L1 expression, level of tumor-infiltrating lymphocytes and comorbidities had no impact. In terms of OS, an ECOG 2 (p < 0.001), PD during chemotherapy (p = 0.037), lack of irAE (p = 0.026), NLR of ≥3.1 (p < 0.001), PLT of ≥409 109 /L (p = 0.011), and PLR of ≥183 (p = 0.018) were negative prognostic factors.
ECOG 2 (hazard ratio [HR] 72.63, 95% CI 6.64–794.4; p <0.001), PD during chemotherapy (HR 8.18, 95% CI 1.32–50.4; p = 0.024), and a PLT >409 109 /L (HR 6.18, 95% CI 1.35–28.32; p = 0.019) were independent prognostic factors for OS in multivariate analysis.
Conclusion
Pembrolizumab produces durable benefit in 20% of pts with pretreated NSCLC. Clinical and laboratory factors may help to indicate subgroups likely to benefit. Poor PS and lack of response to previous chemotherapy are major determinants of worse prognosis.
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P78.10 - Immunotherapy in Non-Small Cell Lung Cancer with High PD-L1 Expression and Coexistent RET- Fusion: The Description of Two Cases. (ID 3718)
00:00 - 00:00 | Presenting Author(s): Magdalena Knetki-Wróblewska
- Abstract
Introduction
Pembrolizumab is widely used as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC) and high expression of PD-L1. The activity of pembrolizumab in NSCLC patients (pts) with rare molecular alterations is poorly characterized. RET rearrangements are identified in 1-2% of NSCLC pts. Two cases of RET-rearranged NSCLC pts with PD-L1>50% treated with pembrolizumab are described.
Methods
Patients were qualified for treatment within routine practice. PD-L1 expression was assessed by immunohistochemistry. RET-fusions was detected in Next Generation Sequencing using FusionPlex Comprehensive Thyroid and Lung (CTL) Kit and sequenced on MiniSeq (Illumina). Efficacy of treatment was assessed according RECIST 1.1
Results
69-year old man, never-smoker, without comorbidities, minimalny symptomatic was diagnosed as stage IV NSCLC adenocarcinoma -PD-L1 90%, RET-fusion KIF5B [15]-RET[12] was found. Pembrolizumab (200mg i.v. every 21 days) was initiated. Two months later pathological fracture of Th10 was diagnosed. CT scan revealed progressive disease (PD)within the liver and both lungs. Despite palliative chest radiotherapy rapid clinical deterioration occurred. The patient died 3 months after the diagnosis.
65-year old woman, never-smoker, without comorbidities was diagnosed as stage IV NSCLC adenocarcinoma - PD-L1 70%, RET-fusion CCDC6 [1]-RET[12] was found. Pembrolizumab was administered, but 3 months later PD was found (mediastinal lymph nodes progression, new lung nodules, bone lesions and liver metastases). Palliative chest radiotherapy was delivered. No active treatment was offered and best supportive care was initiated afterwards.
Conclusion
Despite the high PD-L expression (observed seldom in patients with RET abnormalities) no benefit of immunotherapy was observed in our patients. The optimal treatment for patients with RET fusion is nowadays a targeted therapy. Unfortunately, it was unavailable when both patients were qualified for the treatment.
