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Alexander John Vickers
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MA22 - New Therapeutics, Pathology, and Brain Metastases for Small Cell and Neuroendocrine Tumour (ID 925)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 15:15 - 16:45, Room 206 BD
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MA22.03 - SCLC Circulating Tumour Cell Derived Explants: The Clinical Characteristics of Patients Whose Samples Generate CDX (ID 12969)
15:25 - 15:30 | Presenting Author(s): Alexander John Vickers
- Abstract
- Presentation
Background
Small cell lung cancer (SCLC) prognosis is dismal, with minimal improvement in recent years. Work with SCLC cell lines and targeted therapies have been disappointing when translated into clinical practice. Circulating tumour cells (CTCs) represent a readily accessible liquid biopsy, which can be used to generate CTC derived explants (CDXs) for the study of SCLC biology and the investigation of biomarkers and therapeutics. These clinically relevant models appear to mirror patient response to therapeutics. Our aim was to assess if the patients whose samples generated a CDX represent the SCLC population, and determine if the clinical features of these patients offer insight into CTC biology.
a9ded1e5ce5d75814730bb4caaf49419 Method
This was a single centre, retrospective analysis of 147 SCLC patients who had participated in The CHEMORES Study in which SCLC patients were asked to donate blood samples for the discovery and validation of novel biomarkers. Paired patient blood samples were taken for CTC enumeration using CellSearch Technology and for attempted CDX model generation. We obtained demographic and clinical information on these patients, and analysed the data for differences between patients whose blood samples generated a CDX and those whose did not.
4c3880bb027f159e801041b1021e88e8 Result
231 paired blood samples were taken from 147 patients, with 45 CDXs successfully generated from 34 patients. CTC number was significantly higher in samples which generated a CDX than those which didn’t, p=0.001. Successful progression samples had a significantly lower CTC number than successful baseline samples, p=0.026. There was no significant difference in age, gender, pack year history, performance status, stage, chemosensitivity or the presence of liver or brain metastases between patients whose samples did and did not generate a CDX. Metastatic burden was significantly higher in patients whose samples generated a CDX, p=<0.001. Progression free (PFS) and overall survival were significantly shorter in patients whose samples generated a CDX, p=<0.001
8eea62084ca7e541d918e823422bd82e Conclusion
CTC number correlates with CDX success, although a specific CTC phenotype may be more important. CTCs at progression may have a more aggressive phenotype than those at baseline. CDXs appeared to represent the SCLC population which is important when translating knowledge gained by studying CDXs into clinical practice. CTCs may play a role in the widespread metastatic dissemination of SCLC and thus survival of patients. Shortened PFS in the absence of difference in chemosensitivity may be due to outliers with particularly long PFS in the unsuccessful group. Further genomic and phenotypic analysis of subpopulations of CTCs may provide further insight.
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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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-26 - Single-Centre Experience of Clinical Outcomes for Advanced Lung Cancer Patients in Phase I Clinical Trials. (ID 13932)
16:45 - 18:00 | Author(s): Alexander John Vickers
- Abstract
Background
Response rates for patients enrolled in early phase clinical trials have historically been reported as 5-10%. An unprecedented number of novel therapeutic options and emerging therapies in lung cancer (LC) have resulted in greater emphasis on early phase clinical trials and molecular stratification.
We aimed to evaluate outcomes for patients with LC treated since 2015 with novel agents or combination strategies within an expanding early phase clinical trials unit at The Christie Hospital, Manchester, UK.
a9ded1e5ce5d75814730bb4caaf49419 Method
A database of patients consented to phase I clinical trials was interrogated for LC patients recruited over a three-year period. Clinical characteristics including histological sub-type, line of therapy, molecular phenotype, smoking status and ECOG performance status (PS) were collected for each patient. Patient records were reviewed for clinical trial allocation, treatment response, progression-free survival (PFS), and overall survival (OS).
4c3880bb027f159e801041b1021e88e8 Result
Over a three-year period to March 2018, 153 lung cancer patients were consented to Phase I clinical trials of Investigational Medicinal Products, of whom 113 (74%) commenced treatment. The median age of patients treated was 64y (range 28-84) with a male predominance (54%). All patients had a PS of 0-1 and 25% were non-smokers. Histological subtypes included non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and mesothelioma. The overall response rate (RR) by RECIST criteria was 27% across all patients, with a disease control rate of 73%. Median PFS was 6 months, and median OS was 11 months in the entire cohort. Compared with patients with NSCLC, patients with SCLC had worse PFS (7mo vs 3mo, p=0.001) and RR (35% vs 0%). The 28 trials recruiting LC patients in the unit during this period involved therapies targeting EGFR and ROS1, PI3K-mTOR-AKT and RAS-RAF-MEK signalling, DNA repair genes, cell-surface protein overexpression and genes implicated in immune signalling. Novel agents included small molecule inhibitors, monoclonal antibodies, and antibody-drug conjugates, in addition to targeted agents combined with chemotherapy or immune checkpoint inhibitor combinations. Patients had between 0-5 prior lines of therapy with no difference in PFS, OS or RR regardless of prior treatment lines.
8eea62084ca7e541d918e823422bd82e Conclusion
Our data demonstrate clear benefit for lung cancer patient participation in early phase clinical trials. Novel therapeutic agents and evolution of early phase clinical trial design have resulted in promising options for patients with NSCLC, with RR>30% within our unit, regardless of prior treatment status. However, outcomes for SCLC patients lag behind and new therapeutic options are urgently needed.
6f8b794f3246b0c1e1780bb4d4d5dc53
