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J.R. Goffin
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MO12 - Prognostic and Predictive Biomarkers III (ID 96)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:B. Han, M. Edelman
- Coordinates: 10/29/2013, 10:30 - 12:00, Parkside Ballroom B, Level 1
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MO12.04 - Biomarker Analysis of NCIC Clinical Trials Group IND.196, a Phase I study of erlotinib plus foretinib in advanced pretreated non-small cell lung cancer patients (ID 3148)
10:45 - 10:50 | Author(s): J.R. Goffin
- Abstract
- Presentation
Background
Upregulation of MET and more recently AXL have been described as potential mechanisms of resistance to EGFR tyrosine kinase inhibitors in NSCLC. We explored the impact of baseline MET and AXL tumour expression and circulating hepatocyte growth factor levels, (HGF), in advanced NSCLC patients receiving erlotinib plus foretinib, an oral multi-targeted kinase inhibitor of MET, RON, AXL, TIE-2 and VEGFR.Methods
Advanced NSCLC patients that previously received one or two lines of chemotherapy were treated in IND.196, a phase I dose-finding trial with an initial two-week run-in of single agent erlotinib (100-150 mg daily). If erlotinib was well tolerated, foretinib was then added (30-45 mg daily). Submission of tumour samples (archival or fresh) was mandatory, and circulating HGF levels were determined at baseline and on treatment. Tumour samples were genotyped using Sequenom MassARRAY analysis. MET and AXL expression were determined by immunohistochemistry. For AXL, the human Axl affinity purified polyclonal goat IgG antibody (R&D systems, AF154, Minneapolis MN) was scored manually. For MET, the anti-total MET (SP-44) rabbit monoclonal antibody (Ventana Medical Systems, Tucson AZ) was scored using the Benchmark XT autostainer. Staining intensity (0-3+) and percent cells stained were used to calculate the H-score; H-scores >100 were deemed positive for AXL, and >200 positive for MET.Results
Of 31 patients enrolled, 28 were evaluable for response to combination therapy, with a recommended phase II dose of erlotinib 150 mg daily for a 2-week run-in and then foretinib 30 mg daily added. The overall response rate in the intent to treat population (RECIST 1.1) was 16.1% (95% CI 5.5-33.7%), with partial responses (PR) seen in 5/31 patients and a median response duration of 17.9 months (range 3.6-17.9). Stable disease was seen in 42% (13/31), with a median duration of 4.8 months (95% CI 2.4-15.4). Tumour samples were submitted for 25 patients; 15 had sufficient tissue for genotyping, 17 for assessment of MET, and 16 for AXL expression. 2/5 responding patients had confirmed EGFR mutations, (1 wildtype, 2 unknown). Another 5 had KRAS mutations, one with >20% reduction in tumour size but SD by RECIST. Of 17 patients with MET IHC results, 71% (12/17) were positive. PR was seen in 3/12 patients with MET-positive tumours, (2 with EGFR mutations, 1 wildtype). No response was seen in those with MET-negative tumours. Of 16 samples with AXL IHC results, 9 were positive (56%). PR was seen in 2/9 with AXL-positive tumours and 2/6 with AXL-negative tumours. AXL expression was not seen in samples with EGFR mutations, but 3/5 KRAS mutant samples were AXL positive. Assessment of circulating HGF levels will be presented at the 2013 WCLC meeting.Conclusion
Baseline MET expression, uncontrolled for EGFR status, may be associated with response to combination erlotinib/foretinib. No correlation between baseline AXL expression and response was seen although the sample size is small. Further study is needed to control for the impact of EGFR mutation status on response, and to assess whether combination erlotinib/foretinib can overcome resistance to EGFR TKI therapy mediated by MET and AXL.Only 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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O05 - Cancer Control (ID 130)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Prevention & Epidemiology
- Presentations: 1
- Moderators:N. Van Zandwijk, A. McWilliams
- Coordinates: 10/28/2013, 10:30 - 12:00, Bayside Auditorium A, Level 1
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O05.05 - Biennial lung cancer screening by low-dose CT scan - a simulation of cost effectiveness in Canada (ID 2313)
11:15 - 11:25 | Author(s): J.R. Goffin
- Abstract
- Presentation
Background
Randomized data support annual screening for lung cancer among smokers using low-dose CT scans. To compare the resource implications of annual versus biennial screening, a cost-effectiveness analysis was undertaken using the Cancer Risk Management Model (CRMM version 2.0.1) in the context of the Canadian publicly funded healthcare system.Methods
The CRMM performs simulations at an individual level and incorporates demographic data, cancer risk factors, cancer registry data, diagnostic and treatment algorithms and health utilities. Outputs are aggregated and costs (in 2008 Cdn dollars) and life-years are discounted at 3% annually. Simulations were performed with a cohort 55-74 years and a ≥30 pack-year (p-y) smoking history recruited from 2012-2032. CT scan sensitivity (Sens) and specificity (Spec) and cohort outcomes were based on NLST and Canadian data. It was assumed 60% of the eligible population participates by 10 years, 70% adhere to the screening regimen, and smoking cessation rates are unchanged. Sensitivity analysis was undertaken.Results
An annual screening program incurs net costs of $2.97 billion and saves 55,000 quality-adjusted life-years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $53,700 per QALY. Under default biennial screening assumptions (Table 1, scenario 3), biennial screening costs are $1.81 billion, saving 32,000 QALYs and producing an ICER of $56,200. In the least favourable stage shift scenario (1) tested, the ICER is $275,000, whereas the most favourable shift (4) results in $49,300. Using Sens/Spec 0.90/0.73 for all scans in scenario 3 produces an ICER of $61,400, whereas changing all incidence scan Sens/Spec to 0.87/0.73 gives an ICER of $60,900. Increasing age of eligibility to 55-79 cost $2.25 billion at an ICER of $58,700 per QALY while requiring a 40 p-y smoking history reduced cost to $1.3 billion at an ICER of $49,800 per QALY. Table 1.
T0, T1 refer to the NLST stage shift at specified time, where T0 equals shift at time zero screen, T1 shift at 12 month screen. T0/T1 indicates an average. CD: the unscreened Canadian stage distribution. PS: NLST post-screening stage shift. *Represents 3[rd] year and all future odd years. **Represents 4[th] year and all future even years. Hyphens indicate years without screening.Year Stage Shift Scenario Sens/ Spec 1 2 3 4 5 0 T0 T0 T0 T0 T0 0.9/0.73 1 CD PS PS PS CD - 2 T0 T0 T0/T1 T1 T1 0.89/0.84 3* CD PS PS PS CD - 4** T0 T0 T0/T1 T1 T1 0.89/0.84 ICER $275,000 $65,000 $56,200 $49,300 $104,00 Conclusion
Compared to annual lung cancer screening, biennial screening reduces net cost but may have a similar ICER. Stage shift assumptions have a significant impact on ICER values. Minor adjustments in Sens/Spec modestly change the ICER. Widening the age range increases but increasing the p-y requirement reduces system costs.Only 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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O06 - Cancer Control and Epidemiology I (ID 135)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Prevention & Epidemiology
- Presentations: 1
- Moderators:C. Dresler, C. Zhou
- Coordinates: 10/28/2013, 10:30 - 12:00, Bayside 104, Level 1
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O06.06 - Factors Associated with Smoking Cessation in Participants of The Pan Canadian Early Lung Cancer Study (ID 1469)
11:35 - 11:45 | Author(s): J.R. Goffin
- Abstract
- Presentation
Background
Lung cancer screening programs provide unique opportunities to facilitate smoking cessation in smokers who participate in these programs. However, the effects of screening on motivation to quit might be mediated or modified by other variables. Identifying the participants more likely to quit will allow rapid application of smoking cessation resources to these participants, while those least likely to quit can be afforded experimental interventions. The aim of our study was to assess the impact of lung cancer screening on smoking cessation in current smokers at the time of enrollment and to identify factors that were associated with quitting smoking in this screening population.Methods
Using data collected from the Pan-Canadian Study of Early Detection of Lung Cancer, both univariate and multivariable logistic regression analysis was used to identify predictors of smoking cessation among current smokers at enrolment. Smoking cessation was defined as quitting for at least a 6 month period, occurring anytime after enrolment.Results
We analyzed baseline and follow-up questionnaires of 2320 participants, of which 1419 were current smokers. Of these 1419 patients, 392 (27.8%) met the definition of smoking cessation during a median of two annual follow-up visits. In both univariate and multivariable (MV) analysis, greater smoking cessation was associated with four factors: (i) having a diagnosis of lung cancer at any time during the screening process, with a MV Odds ratio (OR) of quitting of 2.4 (95%CI: 1.1-5.0); (ii) lower and medium nicotine addiction as assessed by the Fagerström Nicotine Dependence Scale Score, with MV-ORs of 3.2 (95%CI: 2.2-4.6) and 1.4 (95%CI: 0.9-2.0), respectively; (iii) having higher education, with MV-OR: 1.4 (95%CI: 1.1-1.9); and (iv) having an earlier age of onset of regular alcohol intake, with MV-OR of 1.11 (95%CI: 1.02-1.21) per 5 year decrease in age. Smoking cessation was also associated with (i) previous attempts of quitting [UV-OR 1.8 (95%CI: 1.2-2.7)], willingness to quit smoking within the next month (at baseline screening) [UV-OR 2.2 (95%CI: 1.8-2.9)] or within the next 6 months after baseline screening [UV-OR 1.8 (95%CI: 1.3.-2.4)]. Second-hand smoking exposure, including exposure as a child, or as an adult at work, at home, privately with friends, or in public settings, or a cumulative index of these different exposures, was not associated with smoking cessation. Presence of potential index symptoms for lung disease, including shortness of breath, cough (both dry and productive), hoarseness, audible wheezing or even chest pain, was not associated with an increased chance of smoking cessation.Conclusion
The diagnosis of a new lung cancer had a major positive impact on screening participants quitting smoking, as were factors such as lower nicotine dependence, higher education, earlier starting alcohol drinking age, and willingness to quit. Whether a new lung cancer diagnosis triggered additional efforts by clinicians to help the person quit will be explored further. Individual lung symptoms and secondhand smoke exposure were not associated with smoking cessation. (Geoffrey Liu and Martin Tamemmagi are co-senior authors)Only 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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O19 - Support and Palliation I (ID 138)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Nurses
- Presentations: 1
- Moderators:Y. Chen, J. Ingham
- Coordinates: 10/29/2013, 10:30 - 12:00, Bayside 104, Level 1
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O19.07 - Resource utilization in the last three months of life by lung cancer patients in the Hamilton-Niagara-Haldimand-Brant Local Health Integration Network (LHIN) (ID 1669)
11:35 - 11:45 | Author(s): J.R. Goffin
- Abstract
- Presentation
Background
Data from the Ontario Cancer System Quality Index demonstrate a high use of Emergency Department (ED) services by lung cancer patients in the last three months of life. There is a need to better understand the resource utilization of lung cancer patients during this time period.Methods
A retrospective cohort study was undertaken to evaluate resource utilization in the last three months of life for new patients with lung cancer seen at the Juravinski and Walker Family Cancer Centres between January and June 2011and deceased prior to July 2012. Data abstracted from patient records included demographics, staging, treatment, referral to palliative care, use of community services, visits to the cancer centre and family doctor, visits to the emergency department and hospitalizations in the last three months of life. The primary outcome was the proportion of patients using the ED in the last three months of life. Secondary outcomes include the proportion of patients hospitalized, place of death, and the use of community and palliative care services.Results
There were 323 new patients seen during the six month period and 162 were deceased at the time of data cut-off. There were 86 men (53%) and 76 women (47%), with a median age at diagnosis was 68.9 years (range 38-90). The majority were married (66%), but 20% were living alone. Twenty percent of patients had SCLC, 73% NSCLC and 7% did not have tissue diagnosis. Most patients (n=141, 87%) were treated with palliative intent from the outset. Chemotherapy was administered to 63 patients (39%) with 11 (7%) receiving chemotherapy within the last 2 weeks of life. A greater proportion of patients received radiation therapy (n=111, 69% [10% radical, 90% palliative]). The median overall survival was 4.1 months (95%CI 3.4-4.8m). The majority of patients (n=132, 82%) were referred to community care services (CCAC) and most of these received community palliative services (n=113, 70%). The median time from CCAC referral to death was 2.5 months (0.3 – 31 months). There was documentation about a change in goal from active treatment to supportive care in 38% of patients and documentation of end of life discussion in 66% of patients. Place of death was: hospital (51%), home (21%), hospice/palliative care institution (20%), unknown (8%). During the last three months of life 93% visited the cancer centre (median visits 2, range 0-10) and 67% made calls to the cancer centre (median 1, range 0-19). Visits to the ED were made by 118 patients (73%, median visits 1, range 1-9) and 36 patients were hospitalized (22%, median 1, range 1-5). Patients referred to CCAC were less likely to visit the ED (72% v 83%, p=0.2).Conclusion
Lung cancer patients use considerable range of services during the last three months of life. Use of acute care services such as the ED and hospitalizations are common. CCAC referral has a small impact on the use of acute care services.Only 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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P2.10 - Poster Session 2 - Chemotherapy (ID 207)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:
- Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P2.10-029 - Educating community health professionals about lung cancer: A pilot evaluation of a web-based educational tool (ID 1663)
09:30 - 09:30 | Author(s): J.R. Goffin
- Abstract
Background
Previous research demonstrated significant delays from the onset of lung cancer symptoms to diagnosis and commencement of treatment. This has potential to influence the outcome of treatment. However, the diagnosis of lung cancer is complicated by considerable overlap between lung cancer symptoms and those of other common respiratory illnesses such as COPD. We sought to evaluate the impact of education of community health professionals about lung cancer on perception of knowledge.Methods
A web-based educational program was developed by expert panel, to disseminate information about lung cancer. Interactive small group workshops were organized within local communities targeting primary care physicians and primary care nurses involved in the initial evaluation of patients with suspected lung cancer. The web-based application covered lung cancer statistics, presenting symptoms, frequently asked questions, links to the new diagnostic assessment program, and key advances in treatment. Invitations were sent to all family physicians in the Hamilton and Haldimand regions of Ontario to attend a pilot session. Pre and post questionnaires were administered to assess the utility of the educational program. Follow up questionnaires were mailed out after six months to evaluate the value of the educational program.Results
Education sessions were conducted in six family practice offices and one occupational health practice, involving 67 health professionals. There were 46 pre and 40 post intervention questionnaires completed (24 physicians, 10 nurses and 12 other). Responses were similar between city (n=20) and rural-based (n=26) health professionals. All respondents felt the educational session was beneficial to attend. Over 85% of respondents agreed the information was clear and easy to understand, of sufficient detail and relevant to practice. Most respondents (88%) felt they would use the web-based tool personally and 90% felt they would use it for patient education. Following the educational intervention, there was some improvement in respondents’ assessment of their knowledge about lung cancer: understanding and background knowledge about lung cancer (79% v 90%); common presenting symptoms of lung cancer (81% v 92%); understand steps needed to diagnose lung cancer (79% v 80%), standard approach to treatment of lung cancer (52% v 95%); recent advances in treatment of lung cancer (19% v 92%). Six month follow up questionnaires were sent to 45 individuals, with 31 replies. Only 4 respondents (13%) had used the web-based tool. The most commonly used section was on the treatment of lung cancer. The majority of respondents (52%) had not seen a lung cancer patient during this time period. Other reasons included for not using the program included: no need (7%), insufficient time (15%), and did not think about it (11%). Respondents’ assessment of their lung cancer knowledge was lower at six months (range 45%-80%).Conclusion
have shown that it is feasible to implement a web-based lung cancer interventional program in family practice. This may improve short term knowledge about lung cancer, but this does not appear sustained at six months. One limitation to the utility of this program is the relative infrequency of lung cancer patients seen by individual family physicians.
