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Vanina Wainsztein
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-76 - Oncomine Tumor Mutation Load Assay in NSCLC Patients from Argentina: Study Design and Feasibility (Now Available) (ID 2733)
08:00 - 18:00 | Author(s): Vanina Wainsztein
- Abstract
Background
High throughput next generation sequencing has improved the understanding of the genomic landscape of cancer. Somatic mutations throughout the exome derive in novel peptide sequences that can be recognized by the host immune system and drive immune responses in patients. The tumor mutational load (TML) is the number of somatic mutations per megabase of DNA and is an emerging biomarker to predict response to immune checkpoint inhibitors.
Method
The objective of this study was to evaluate the feasibility of assessing TML in tumors from patients with advanced NSCLC, treated with Nivolumab in second with Ion Torrent™ Oncomine™ TML Assay and compare it with TML from WES. The Oncomine TML is a targeted NGS assay that provides quantification of somatic mutations, from limited formalin-fixed, paraffin-embedded (FFPE) samples.
Result
DNA was purified with QIAamp DNA FFPE Tissue Kit (QIAGEN). We used a new Ion AmpliSeq targeted panel, derived from the Comprehensive Cancer Panel which covers approximately 1.7 Mb of genomic DNA and 409 genes, OTML in S5, Ion Proton (Life Technologies); and WES were performed in NovaSeq 6000 Sequencing System (Illumina). We included 40 patients with advanced NSCLC. 27 (68%) of patients had both, tumor and normal tissue to perform WES. FFPE samples were obtained from lungs (N=21), lymph nodes (N=11), pleura (N= 3), brain (N=1), skin (N= 1), bone marrow (N = 1), soft tissue (N=1). We used 20 ng of DNA to develop the manual library and templating. We covered a large genomic footprint to accurately measure somatic mutations, replacing the need for whole-exome sequencing (WES). Pipeline for analysis of the NGS output will be presented.
Conclusion
TML estimation with low DNA input requirements from FFPE samples is feasible. Up to 8 samples can be sequenced in a Ion 540™ Chip. Mutation load assessment can be done within 2–3 days. This assay was highly reproducible in FFPE samples. A detailed report provides normalized mutation count per MB as well as mutation signatures.
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P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.16-10 - Real-World Efficacy of First-Line Pembrolizumab in Patients with Advanced PD-L1 High Non-Small Cell Lung Cancer in Argentina (Now Available) (ID 1440)
09:45 - 18:00 | Author(s): Vanina Wainsztein
- Abstract
Background
Pembrolizumab monotherapy is a standard first-line (1L) treatment regimen for patients (pts) with non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) ≥ 50%. We aimed to study the clinical efficacy and toxicity of this approach in the real-world setting in Argentina.
Method
We conducted a retrospective, multicenter study. Patients with metastatic NSCLC and a PD-L1 TPS ≥ 50% treated in 1L with at least one dose of pembrolizumab monotherapy, from December 2016 to February 2019, were included. Data was collected from clinical records, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were estimated. Cox regression model was performed for uni- and multivariate analysis.
Result
A total of 53 pts were included. Median age (range) was 68 years (35-88), 33 (62.3%) were male, and 46 pts (86.7%) were smokers. Most tumors were lung adenocarcinoma (N=47, 88.7%), median (IQR) PD-L1 TPS was 79% (60-87.5) and 22 tumors (41.5%) had a TPS ≥ 75%. EGFR/ALK/ROS1 mutations/fusions were not detected. Brain (N=10; 18.9%), liver (N=5 (9.4%) and bone (N=15; 28.3%) metastasis were present at baseline. Performance status (PS) score was 0-1 in 46 pts (86.8%) and 7 pts (13.2%) had PS 2. Six pts received baseline corticosteroid treatment. The ORR with pembrolizumab was 41.5% (95% CI: 28.1-55.8), median PD-L1 TPS (mTPS) was significantly higher in responders (mTPS 74% vs 67%, P = 0.04). Grade ≥ 3 immune-related adverse events occurred in 7 pts (13.2%) and 10 (18.9%) required systemic therapy with steroids. With a median-follow up of 12.9 months (95% CI: 8.4-17.6), median PFS and median OS were not reached. The estimated percentage of patients alive and without progression at 6 and 12 months was 64.8% and 55.8%. The estimated percentage of patients alive at 6 and 12 months was 77.5% and 69.4%. Median PFS and OS for patients with PS 2 was 2.4 months (95% CI: 1.7-3.1) and 4.5 months (95% CI: 3.1-6.0), respectively. After adjusting for PS, a PDL1 TPS score ≥ 75% was independently associated with improved PFS in multivariate analysis [HR 0.28 (95% CI: 0.09-0.92); P = 0.03) but not with OS. PS score equal to 2 was independently associated with decreased OS [HR 4.52 (95% CI: 1.06-19.28); P = 0.04] in multivariate analysis.
Conclusion
Pembrolizumab monotherapy is tolerable and confers durable clinical benefit for patients with tumors expressing high levels of PD-L1 in the real world clinical setting. The optimal first-line immunotherapy approach for patients with PS 2 in this setting warrants further studies.
