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M. Ilouze
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-039 - Survival Impact of Next-Generation Sequencing in Lung Cancer (ID 10212)
09:30 - 09:30 | Author(s): M. Ilouze
- Abstract
Background:
Next-generation sequencing (NGS) enables a comprehensive genomic analysis of lung cancer patients. It has uncovered many novel genetic abnormalities and identified actionable genomic alterations in lung tumors that previously tested "negative" by conventional non-NGS tests. In this study, we evaluated the clinical impact of NGS, performed at different stages of the oncologic management, on overall survival of advanced lung cancer patients.
Method:
In this retrospective study, 178 consecutive non-small cell lung cancer (NSCLC) patients who performed hybrid capturing NGS were enrolled at the Thoracic Cancer Unit at Rabin Medical Center, Israel, between 2011-2017. Hybrid capture-based NGS was performed by Foundation Medicine and Gaurdant 360[TM] if tissue was not available.
Result:
178 consecutive NSCLC patients were included in this study. Median age at diagnosis was 63±12.1 years. 83% had adenocarcinoma. NGS was performed upfront in 45.5% (81/178) and after 1[st] line failure in 54.5% (97/178). Treatment decision was taken toward targeted therapy subsequent to NGS analysis in 34% (61/178) of patients (29 and 32 respectively) with an objective response rate of 54%. Overall survival (OS) was evaluated for 51% (31/61) with a median of 12.2±14.1 months. For patients who performed upfront NGS, OS ranged between 1.8 to 32.5 months, with a median OS of 13.8 months. For patients who performed NGS on progression, OS ranged between 1.7 to 77.1, with a median OS of 12.7 months.
Conclusion:
Comprehensive tissue and liquid-based NGS have revealed targeted treatment options for one third of the patients. Overall Survival of patients treated with tailored therapy was positively impacted by earlier performed NGS.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-056 - Intracranial Activity of Osimertinib in Naïve EGFRm T790M(-)And Treated EGFRm T790M(+) NSCLC Patients with Asymptomatic Brain Metastases (ID 9819)
09:30 - 09:30 | Author(s): M. Ilouze
- Abstract
Background:
Osimertinib is an effective, irreversible EGFR-TKI selective for EGFR-TKI-sensitizing (EGFRm) and T790M[+] resistance mutations. Intracranial activity of osimertinib has been reported in T790M[+] patients; however its activity in EGFR-TKI naïve setting has not been investigated yet. Here, we present preliminary data of a phase II study assessing the intracranial activity of osimertinib in EGFRm NSCLC patients with asymptomatic brain metastases as 1[st] line therapy for naïve patients and as 2[nd] line therapy for EGFRm patients who progressed on EGFR TKI and harbor T790M[+]. Dose escalation from 80 mg QD to 160 mg QD was allowed in cases of brain progression.
Method:
A phase II, open label, two arm study is presented. Treatment-naïve (arm A) advanced NSCLC with sensitizing EGFRm and previously treated (arm B) with 1[st] or 2[nd]-generation EGFR TKIs (gefitinib, erlotinib or afatinib) in whom T790M[+] was diagnosed were enrolled to this study. Intracranial response was assessed by brain MRI scans every 6 weeks and systemic evaluation by PET-CT scan every 3 months unttil progression. The study plans to enroll 20 patients in each arm aiming to reach a statistical power of 0.8.
Result:
As of May 31 2017, 22 patients were enrolled; 15 patients in arm A and 7 patients in arm B, age 67.8±10.4 years, 14 females and 8 males. Preliminary outcome analysis is presented for 16 patients with a median follow up of 6.1 months (range 1.4-11.4 months). On May 31[st] 2017 data cut-off was performed. The Intracranial response rate (ICRR) was 81% (13/16 pts); 82% (9/11 pts) in arm A and 80% (4/5 pts) in arm B. Time to response was 6 weeks (1[st] MRI) in all responding patients. Intracranial disease control rate (IDCR) was 81% (13/16 pts) for the current follow up time of 6.1 months; median PFS not reached. Dose escalation was performed in 2 cases and data is not mature yet. Toxicity profile is similar to previous reported data.
Conclusion:
Osimertinib shows a promising intracranial response rate in naïve EGFRm NSCLC patients (82% ICRR) and in 2[nd] line T790M (+) setting with 80% ICRR. This study is still recruiting.
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P3.01-060 - The Clinical Utility of ctDNA Gene Analysis in Lung Cancer (ID 9948)
09:30 - 09:30 | Author(s): M. Ilouze
- Abstract
Background:
Next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) enables a non-invasive option for comprehensive genomic analysis of lung cancer patients. In this study, we evaluated the impact of ctDNA sequencing on outcomes and treatment strategy.
Method:
In this retrospective study, data was collected from files of advanced non-small cell lung cancer (NSCLC) patients at the Thoracic Cancer Unit, Rabin Medical Center, Israel, between 2014-2017. Plasma samples were analyzed by a commercial test (Guardant360[TM]), using massively parallel paired-end synthesis to sequence a targeted 68-73 gene panel.
Result:
116 consecutive NSCLC patients were included in this study. Median age at diagnosis was 63 years, 74% had adenocarcinoma. 41% performed ctDNA analysis before 1st line therapy (Group A) and 59% on progression (Group B), among them 41% after progression on EGFR TKIs (Group B1) and 59% on other treatments (Group B2). ctDNA analysis yielded actionable mutations (EGFR, ALK, RET, BRAF, MET, ERBB2 (HER2)) in 40.5%: 31% in group A, 47% in group B, 71% in group B1 and 30% in group B2. Treatment decision was taken toward targeted therapy subsequent to NGS in 26%.Genetic alterations frequencies among groups A, B, B1 and B2
Response assessment (RECIST) to targeted therapy showed complete response in 4%, partial response in 44%, stable disease in 37% and progressive disease in 15%. Response rate was 44% for group A, 50% for group B, 60% for group B1, 37.5% for group B2. Total objective response rate was 48% and disease control rate was 85%. Overall survival was evaluated for 40%, median was 14.4 months for patients who received targeted therapy vs 13.6 months for patients who received standard treatment.Group A 19 individual mutations Group B 52 individual mutations Group B1 34 individual mutations Group B2 18 individual mutations EGFR Sensitizing 52.5% (10/19) EGFR Sensitizing 42% (22/52) EGFR Sensitizing 59% (20/34) MET 55.6% (10/18) MET 16% (3/19) MET 27% (14/52) EGFR T790M 23% (8/34) ERBB2 16.7% (3/18) ERBB2 10.5% (2/19) EGFR T790M 15% (8/52) MET 12% (4/34) RET 16.7% (3/18) BRAF V600E 10.5% (2/19) ERBB2 8% (4/52) ERBB2 3% (1/34) EGFR Sensitizing 11.1% (2/18) RET 10.5% (2/19) RET 6% (3/52) ALK 3% (1/34) ALK 2% (1/52)
Conclusion:
Comprehensive ctDNA testing revealed treatment options for 40.5% of patients analyzed. The highest impact was seen in progressors on EGFR therapy. These positive results emphasize the utility of liquid biopsy analysis to guide clinicians to select the most efficacious therapy for each patient.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-096 - The Interaction Between Mast Cells and Lung Cancer Cells Through Extracellular Vesicles (ID 10200)
09:30 - 09:30 | Author(s): M. Ilouze
- Abstract
Background:
Exosomes are nano-sized extracellular vesicles that mediate cell-to-cell communication by transferring molecules. Mast cells are secretory cells that complete their differentiation and maturation in the micro-environment of tissues containing blood vessels, and were observed in the periphery of certain tumors. It has been hypothesized that tumor cells affect their environment by passing genetic codes such as miRNA through exosomes. In this study, we investigated the presence of exosomal content in the micro-environment of lung cancer cells as a communication mechanism that drives tumor development.
Method:
Human mast cells (HMC1) were exposed to Human lung cancer cells (H1299) in in vitro setting. Exosomes were isolated from mast cells alone, lung cancer cells alone and from a co-culture of mast cells and lung cancer cells. As a control, exosomes were produced from mast cells that were activated by membranes of lung cancer cells. Exosomes quantity and quality were analyzed including its miRNA composition. Samples were run on an HTG EdgeSeq Processor using the HTG EdgeSeq miRNA WT assay. Each assay contains 2102 probes for miRNA, including 13 housekeeper genes, 5 negative process controls, and 1 positive process control. The HTG EdgeSeq Parser was used to align the FASTQ files to the probe list to collate the data. CPM (counts per million) was normalized and differential expression was analyzed using DESeq2.
Result:
We exposed mast cells to membranes of lung cancer cells, in order to examine induction of mast cells. Out of 2066 miRNA analyzed only 3 were significantly upregulated: miR-31-5p, miR-100-5p and miR-125b-5p. Interestingly, the profile of the pathways activated by these 3 upregulated miRNAs shows the focal adhesion and adherens junctions as one of the top results. A comparison was made between miRNA expression of exosomes from mast cells vs. exosomes from lung cancer cells. Out of 2066 miRNA analyzed, a total of 112 miRNA were differentely expressed. 79 miRNAs were downregulated, for example hsa-miR-6802-5p downregulated in HMC1 in comparison with H1299, and moreover hsa-miR-4700-5p. 33 miRNAs were significantly upregulated, for example miR-146b-5p/miR-146a-5p. Top upregulated miRNAs were tested using KEGG pathway and predicted to lead to the activation of the pathways like viral carcinogenesis, pathways in cancer and cell cycle.
Conclusion:
Mast cells and cancer cells do have common and discriminating exosomal content. Interestingly, mast cells have been induced by the presence of lung cancer cells’ membranes, through a change in the canonical pathways of focal adhesion, by the upregulation of only 3 miRNAs.
