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MA 04 - Advocacy: Listen to the Patients (ID 655)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Patient Advocacy
- Presentations: 1
MA 04.10 - An Assessment of the Willingness to Provide Serial Bio-Specimens: Experience from an Irish Tertiary Cancer Centre (ID 10076)
11:00 - 12:30 | Author(s): D.M. O'Donnell
The rising imperative to improve our understanding of cancer heterogeneity and individualised drug response has led to a high demand for biopsy material. With improvements in technologies, there is now a move away from more traditional tissue based sampling to liquid based biopsies. ‘Liquid biopsies’ provide a non-invasive means for molecularly profiling patients with cancer, thus benefiting patients and clinicians in terms of treatment choice and shared decision-making. We assessed the willingness of patients to undergo repeated tissue and/or ‘liquid’ based sampling.
Detailed questionnaires, assessing patients’ perceptions of, and willingness to undergo serial biopsies were distributed to ambulatory patients at a tertiary cancer referral centre (St. James’s Hospital, Dublin). Multivariate analysis was performed using ordinal logistic regression analysis.
The questionnaire response rate was 97% (247/255). Respondents were primarily female (73%), aged between 51-70 yrs (51%), with breast (39%), colorectal (16%), oesophagogastric (13%), and lung cancer (12%). Of those that responded, repeat biopsy of an easily accessible lesion was acceptable to 203 (82%) patients if recommended by an oncologist. However this reduced to 102 (41%) patients, if the purpose was solely for clinical trial. Acceptability decreased to 168 (68%) and 81 (33%) patients respectively for more invasive biopsies. Additionally, 79 (32%) patients were willing to undergo additional biopsy for research purposes only, with 54 (21%) patients uncertain of its utility in research. Lower performance status (OR=0.44, p=0.04) and the belief that biopsy was unimportant for research (OR=0.74, p=0.04) negatively impacted on willingness to undergo biopsy, while a prior invasive biopsy increased acceptance (OR=1.02, p=0.02). In terms of blood sampling, 82% of patients would consent to repeated blood sampling over the course of their treatment, with >5 samples considered acceptable by 51.5% of patients. Patients with lung cancer had 3.38 greater odds (OR=3.38, p=0.047) of consenting to a repeated blood sample for purely research purposes (compared to any other type of cancer); however their willingness to undergo repeat biopsy was similar to that of other patients (OR=1.99, p=0.129). Data analysis is currently on-going.
Patients with cancer are willing to participate in serial sampling of blood and urine but are less likely to consent to repeated tissue biopsies. Patients with lung cancer were particularly amenable to repeated blood sampling compared to patients with other cancer types. This is significant given the recent data supporting the use of ‘liquid’ biopsy for real-time monitoring of resistance mutations and treatment response dynamics in patients with lung cancer.
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P1.09 - Mesothelioma (ID 695)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
P1.09-007 - Targeting MET/TAM Receptors in Mesothelioma: Are Multi-TKIs Superior to Specific TKI? (ID 9959)
09:30 - 16:00 | Author(s): D.M. O'Donnell
Malignant pleural mesothelioma (MPM) is an aggressive inflammatory cancer associated with exposure to asbestos, and most patients die within 24 months of diagnosis. There is an urgent need to identify new therapies for treating MPM patients. Targeting “addicted” receptor tyrosine kinase (RTK) signalling networks has become a critical therapy option in cancer therapy. RTK hetero-dimerization may however, be a key element in the development of resistance to such therapy. As such Tyrosine kinase inhibitors (TKIs) with the ability to target multiple receptors may have superior efficacy to those targeting individual receptors. We and others have identified c-MET, MST1R (also known as RON), Axl and Tyro3 as RTKs frequently overexpressed and activated in MPM, making these attractive candidate targets. Several agents have been developed which target these. LCRF0004 specifically targets MST1R, whereas BMS-777607, RXDX-106 or Merestinib (LY2801653) are orally bioavailable small molecule inhibitors which inhibit c-MET, MST1R, Axl and Tyro3 at nM concentrations. These drugs may therefore have clinical utility in the treatment/management of MPM.
Expression of RON/MET/TAM and associated ligands were assessed in a cohort of patient samples and MPM cell lines comprising benign, epithelial, biphasic, and sarcomatoid histologies. In vitro and in vivo experiments were undertaken to determine the efficacy of single and multi RTK targeting agents (LCRF0004, RXDX-106, BMS-777607). The effects of LCRF0004 and BMS-777607 were subsequently examined in an in vivo SQ xenograft tumour model.
mRNA expression of the RON/MET/TAM family and associated ligands (MSP, GAS6) was detected in a large panel of normal pleural and MPM cell lines. In a cohort of patient samples, mRNA levels of c-MET, Axl, Tyro3 and various isoforms of MST1R (flRON, sfRON, t-ΔRON) and MSP but not Gas6 or MERTK were increased in tumours compared with benign pleural samples (p<0.05). No MET Exon 14 skipping mutations were detected. RTK targeting agents displayed in vitro efficacy in terms of reduced proliferation. In vivo, the multi-target TKI (BMS-777607) demonstrated superior anti-tumour activity compared with LCRF0004 (MST1R specific compound). IHC analysis of the xenograft tumours showed high cytoplasmic expression of Vimentin, Cytokeratin and Calretinin, with significant necrosis in many.
Our data suggests that a multi-TKI, targeting the RON/MET/TAM signalling network, is superior to selective RTK inhibition as an interventional strategy in MPM.