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Gwyn Bebb
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MA02 - Improving Outcomes for Patients with Lung Cancer (ID 895)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 201 BD
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MA02.11 - Achieving Value in Cancer Diagnostics: Blood Versus Tissue Molecular Profiling - A Prospective Canadian Study (VALUE) (ID 13611)
11:40 - 11:45 | Author(s): Gwyn Bebb
- Abstract
- Presentation
Background
Cell-free DNA (cfDNA) next-generation sequencing (NGS) has emerged as an effective molecular profiling technique that is potentially faster and cost-saving in comparison to standard-of-care (SOC) tumour biopsy and tissue-based profiling. In a public payer system, the added value of cfDNA blood-based profiling compared to SOC remains unknown. This study will determine the incremental clinical utility and cost of cfDNA NGS versus SOC genotyping in patients with advanced non-squamous non-small cell lung cancer (NSCLC).
a9ded1e5ce5d75814730bb4caaf49419 Method
This multicentre, non-randomized, longitudinal study will be conducted at 6 sites across Canada (BC, Alberta, Ontario, Quebec). The Guardant360® assay will be used to perform plasma-based cfDNA testing, and includes mutations, rearrangements and copy number variations in 73 known cancer associated genes. Two patient cohorts will be recruited: (1) treatment naïve patients with ≤10 pack year smoking history; and (2) patients with known abnormalities of EGFR, ALK, ROS-1 or BRAF after disease progression on all standard targeted therapies. SOC tissue profiling will be performed for all patients per institutional standards. The study will begin recruiting in May 2018, with estimated completion in 12 months. The primary endpoints are comparison of response rate (RR), progression-free survival (PFS) and time-to-treatment failure (TTF) using cfDNA versus tissue genomic testing. Secondary endpoints include time to treatment initiation, number of actionable genomic abnormalities identified, result turnaround time, potentially avoidable repeat tissue biopsies, costs, patient-reported quality of life (EQ-5D) and willingness-to-pay. Exploratory analyses of treatment outcomes in selected molecular subgroups will also be undertaken, including response to immunotherapy in those with KRAS/STK11 co-mutations. A decision-analytic model will be developed to perform cost-consequence analyses using a cfDNA versus tissue-based approach.
4c3880bb027f159e801041b1021e88e8 Result
A total of 210 patients will be recruited across Canada, (Cohort 1 N=150, Cohort 2 N=60). Based on testing with either blood-based GUARDANT360TM or tissue-based profiling, the costs and benefits of blood-based profiling either at initial diagnosis or upon TKI progression will be determined versus initial or repeat tumour biopsy and tissue-based profiling. Data from patients accrued until 08/2018 will be presented at the meeting.
8eea62084ca7e541d918e823422bd82e Conclusion
This study will determine the added value of cfDNA blood-based genotyping compared to SOC from the perspective of a public payer system (Canada).
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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MA14 - Survivorship, Socioeconomic and End-of-Life Considerations (ID 915)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 10:30 - 12:00, Room 205 BD
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MA14.11 - Factors Associated with Early Mortality in Non-Small Cell Lung Cancer Patients Following Systemic Anti-Cancer Treatment (ID 12970)
11:40 - 11:45 | Author(s): Gwyn Bebb
- Abstract
- Presentation
Background
To determine a 30-day mortality rate benchmark and assess factors associated with early mortality of non-small cell lung cancer (NSCLC) patients following receipt of systemic anti-cancer therapies (SACT).
a9ded1e5ce5d75814730bb4caaf49419 Method
In a 10-year population-based analysis, NSCLC patients receiving SACT in 2005-2014, with or without other treatments, and captured in the Glans-Look Lung Cancer Database, which contains demographic, clinical, pathological, treatment and outcome data were reviewed. 30-day mortality after most recent SACT cycle was calculated, and end-of life (EOL) regimen changes in the last 14 days of life were identified. Univariate analysis and multivariable logistic regression were used to identify demographic, tumor or treatment-related factors that correlated with mortality risk.
4c3880bb027f159e801041b1021e88e8 Result
1044 eligible NSCLC patients receiving at least one cycle of SACT in 2005-2014 were identified. 51% were female, 62% adenocarcinoma, 79% current/former smokers, 83% advanced stage at diagnosis, and 77% receiving palliative-intent treatment. 233 (22.3%) deaths occurred ≤ 30 days following SACT receipt, and 32 (13.7%) EOL regimen changes identified. Risk of early mortality decreased for never-smokers and those receiving SACT between 2010-2014, and increased in association with male gender, advanced disease at diagnosis, palliative-intent treatment, and use of EGFR-targeting agents. No factors were associated with a decreased risk of EOL regimen change. (Table 1). The predominant SACT-modality among those experiencing 30-day mortality was EGFR-targeting agents (54%).
8eea62084ca7e541d918e823422bd82e Conclusion
Our findings from a real-world population identify several factors which affect the risk of early mortality in NSCLC patients following SACT, and establish a 30-day mortality benchmark for Canadian NSCLC populations. Evolving SACT modalities may facilitate an increased use of SACT at EOL and associated early mortality; however, in this cohort, decreased early mortality risk in the 2010-2014 timeframe suggests concomitant evolution of decisions regarding EOL SACT and/or palliative and EOL care may be underway at our centre, but represents an area for ongoing investigation.
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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MA27 - Novel Drugs and PDX Models (ID 931)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 206 BD
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MA27.08 - Discussant - MA 27.05, MA 27.06, MA 27.07 (ID 14581)
14:15 - 14:30 | Presenting Author(s): Gwyn Bebb
- Abstract
- Presentation
Abstract not provided
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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P1.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 944)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.12-10 - Patterns of Curative Chemo-Radiotherapy Regimen and Impacts on the Outcome of Limited Stage SCLC in a Canadian Institution: 2010 – 2015 Diagnoses (ID 13367)
16:45 - 18:00 | Author(s): Gwyn Bebb
- Abstract
Background
Curative intent chemotherapy and radiotherapy (ChemoRT) is the widely recommended treatment for limited stage (LS) small cell lung cancer (SCLC) follow by prophylactic cranial irradiation (PCI) in those who responded to the initial therapy. LS-SCLC is however characterized by high relapse rate with only about 20% surviving to 2 years. Our objective is to examine the characteristics, treatment patterns and overall survival of LS-SCLC for patients diagnosed within a 5-year period at the Tom Baker Cancer Centre, Canada, prior to wide adoption of emerging treatment options including surgery and immunotherapy in the curative and palliative settings respectively.
a9ded1e5ce5d75814730bb4caaf49419 Method
Using the Glans-Look Lung Research (GLR) database, we defined the clinical and demographic features of patients diagnosed with LS-SCLC from 2010 to 2015, determined the rate of systemic treatment uptake, and investigated the impact of PCI, curative intent, and palliative treatments on overall survival. We summarized our findings with descriptive statistics (including Fisher’s Exact test) and Kaplan Meier survival curves using SPSS. Statistical significance was set at p value < 0.05 and 95% confidence intervals.
4c3880bb027f159e801041b1021e88e8 Result
About a third (107/349, 31%) of patients diagnosed with SCLC from 2010 to 2015 were LS-SCLC, with median age of 67 years. Over the 5-year period, systemic treatments uptake rates and patterns fluctuates. Overall, > 50% received ChemoRT and 65% of the ChemoRT group also received PCI. Curative concurrent RT dose 45 – 55Gy, 25 fractions schedule was more common (55%). Few stage T1a-2a, N0-1 LS-SCLC had surgery (5%). Thirty eight percent of those who received initial curative intent treatments further received some palliative treatments for disease recurrence or progression {8% (2/26) initial Surgery ± Adjuvant & 92% (24/26) ChemoRT}. The median overall survival for the cohort was 24 months (p < 0.001). There were more than 50% survival at 60 months for patients treated with curative 15 fractions concurrent ChemoRT (p < 0.001).
8eea62084ca7e541d918e823422bd82e Conclusion
Most patients received ChemoRT while a few had surgery. Concurrent 15 fractions ChemoRT may offer better survival benefits than the 25 fraction schedule. The impact of PCI on LS-SCLC and other survival outcomes will be presented.
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P1.12-11 - 2010 – 2015 Extensive Stage SCLC Diagnoses in a Canadian Institution: Baseline Characteristics That Impact on the Overall Survival (ID 13430)
16:45 - 18:00 | Author(s): Gwyn Bebb
- Abstract
Background
Small cell lung cancer (SCLC) represents only about 13 – 15% of lung cancers but has posed significant challenges due to minimal progress in therapeutics development prior to the recent advent of immunotherapy. Our objective is to establish baseline characteristics and overall survival of Extensive SCLC (ES-SCLC) based on the current conventional therapy for patients diagnosed within a 5 year period at the Tom Baker Cancer Centre, Canada. This information will be crucial in assessing the effectiveness of novel anti-immune checkpoint treatment strategies.
a9ded1e5ce5d75814730bb4caaf49419 Method
Using the Glans-Look Lung Research (GLR) database, we defined the clinical and demographic features of patients diagnosed with ES-SCLC from 2010 to 2015, determined the rate of systemic treatment uptake, and investigated the impact of prophylactic cranial irradiation and palliative treatments on overall survival. We summarized our findings with descriptive statistics (including Fisher’s Exact test) and Kaplan Meier curves using the SPSS. Statistical significance was set at p value < 0.05 and 95% confidence intervals.
4c3880bb027f159e801041b1021e88e8 Result
Among the 2010 to 2015 SCLC diagnoses, 68% (242/349) were ES-SCLC with median age of 68 years. Close to 90% received some form of palliative treatment. Chemotherapy (CT) was a major component of palliative treatments {89% overall, (190/214): 41% CT only, 22% CT & thoracic radiotherapy (RT) and 38% CT & RT-Other sites}. About a third (32%) of patients who received 1st line CT also had a 2nd line (range between 1 – 4 lines). Prophylactic cranial irradiation (PCI) uptake rates were 38% and 11% for CT only and CT & RT respectively. The median overall survival for ES-SCLC within the cohort was 7 months (p < 0.001).
8eea62084ca7e541d918e823422bd82e Conclusion
In contrast to advanced stage non-small cell lung cancers, there was high rate of sytemic treatment uptake for ES-SCLC. Overall however, < 20% (41/242) followed through with PCI. Other outcome findings will be presented and discussed.
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P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- 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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P1.13-22 - Clinical Features and Outcomes of NSCLC Patients with Uncommon EGFR Mutations Treated with EGFR-TKIs (ID 13371)
16:45 - 18:00 | Author(s): Gwyn Bebb
- Abstract
Background
Non-small cell lung cancers with common epidermal-growth factor receptor (EGFR) mutations (exon 19 deletion and exon 21-point mutation L858R) are known to greatly benefit from EGFR-tyrosine kinase inhibitors (TKIs). However, much less is known about the treatment responses of EGFR mutations such as L861Q, G719X and double EGFRmut+ carriers. In this study, we report clinicopathological and treatment outcomes of patients harboring such EGFR mutations and treated with EGFR-TKIs.
a9ded1e5ce5d75814730bb4caaf49419 Method
Between 2009 – 2015, 233 EGFRmut+ NSCLC patients treated at two Alberta-based cancer centres, Tom Baker Cancer Centre (Calgary) and Cross Cancer Institute (Edmonton) were screened retrospectively via the provincial cancer registry and the Glans-Look Lung Cancer Database. Clinicopathological and treatment outcomes were analyzed. Overall survival was assessed using the Kaplan-Meier method and compared using the log-rank test. Outcomes of single versus double EGFRmut+ carrier sub-groups were compared using Fisher’s Exact test.
4c3880bb027f159e801041b1021e88e8 Result
42/233 (18%) patients harbored uncommon EGFR mutations: 14/42 (33%) carried single rare EGFRmut+ and 11/42 (26%) carried double EGFRmut+, meanwhile 41% couldn’t be specified. Most frequently detected uncommon single EGFR mutations were G719X (12%) and L861Q (17%). Table 1 summarizes clinical characteristics and TKI efficacy amongst uncommon EGFR mutations. Compared to single EGFR mutants, double EGFR mutation carriers were older (median age 71yrs vs 69 yrs), have a smoking-history (73% vs 50%), experienced longer median OS and PFS (15 and 12 months p < 0.001, vs. 9 and 3 months p = 0.0014 respectively), and were also more likely to continue with a TKI beyond initial-TKI-PD (82% vs 28%).
8eea62084ca7e541d918e823422bd82e Conclusion
Retrospective real-world data illustrating the experience and outcomes of uncommon EGFR mutation carriers was explored in this study. Additionally, our results, although limited by cohort-size, highlights that tumor responses from TKI treatments vary amongst uncommon EGFRmut+ carriers, with most favorable survival responses observed in double EGFR mutants.
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 3
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-05 - Adenocarcinoma of the Lung: The Woman’s Cancer? (ID 14356)
16:45 - 18:00 | Author(s): Gwyn Bebb
- Abstract
Background
We previously observed a significant interaction between sex and age-standardized incidence rates of Non-small cell lung cancer (NSCLC) patients showing higher rates of Adenocarcinoma (ADC) in women, from the systematic review of published studies within the last 20 years. Our analysis showed disparities across gender over time, and the main effect of gender on incidence rates is significant (p= 0.01). This study aimed to replicate observed sex-related disparities in published records using a 15-year retrospective analysis of a local large-scale database of NSCLC patients diagnosed in Southern Alberta, Canada.
a9ded1e5ce5d75814730bb4caaf49419 Method
We extracted data from the Glans-Look Lung Cancer Database, a comprehensive clinical and demographic database of all lung cancer patients diagnosed in southern Alberta from 1999-2015. We assessed the impacts of gender on NSCLC risks and mortality. Clinical data e.g. smoking history, histology and NSCLC stage were collected and analyzed using chi-square test, and smoking history and tumor stage were stratified for the analysis. The Kaplan-Meier analysis was conducted to compare gender-based post diagnosis survival and disease progression. Statistical significance was 95% confidence level (p < 0.05).
4c3880bb027f159e801041b1021e88e8 Result
Among 7738 lung cancer patients, 95.6% (3743/7738) were NSCLC: 52% male and 48% female. Significant gender-based differences were observed in histology (p=0.00). SCC and ADC were the most frequent histology in both genders. However, ADC was commoner in women (49% vs 41%), while SCC was commoner in men (27% vs 17%). Relative changes of ADC rate over 15 years have increased significantly among women compared to men (58% vs 32%, P<0.02). The risk of developing NSCLC was greatly elevated with cigarette consumption in both genders; however, ADC in never smokers was higher in women (18%) compared to men (8%). Among ADC, smoking history and gender both showed a significant effect on survival, where mOS for never-smokers females exceeded that of never-smokers males [20 months vs 14 months, 95%CI, P=0.00]. The same trend was also seen in smokers [13 months vs 7 months, 95%CI, P=0.021]. In addition, the OS among male ADC cases was significantly lower than women of all tumor stages (P=0.00), but these disparities were insignificant across genders with SCC (P=0.46).
8eea62084ca7e541d918e823422bd82e Conclusion
Similar to what we observed in our systematic review, gender influences the clinical course of NSCLC regardless of smoking history or stage in Southern Alberta. Identifying the cause of the increase in ADC rate over 15 years in women and higher prevalence of NSCLC in never smoking women warrants aggressive research strategies.
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P2.01-13 - Number, Rather Than Location of Metastases, Dictates Outcome in Stage IV, M1b, Non-Small Cell Lung Cancer (ID 12799)
16:45 - 18:00 | Author(s): Gwyn Bebb
- Abstract
Background
To assess the impact of location versus number of extra-pulmonary metastatic sites (EPMS) on survival in stage IV non-small cell lung cancer (NSCLC).
a9ded1e5ce5d75814730bb4caaf49419 Method
A large scale, multi-year retrospective analysis was conducted on patients with a new diagnosis of stage IV, M1b (AJCC 7th edition) NSCLC between 1999-2013. Demographic, clinical, histopathological, treatment and outcome data was extracted from the Canadian institutional Glans-Look Lung Cancer Database. We assessed the impact of location and number of EPMS and identified correlates of overall survival using the Kaplan-Meier method and Cox regression.
4c3880bb027f159e801041b1021e88e8 Result
A total of 2,065 NSCLC patients with EPMS were identified. Median age was 67 (IQR 58-75) years, 52% were male, and 78% reported a history of smoking. 60% had one EPMS, and 40% had two or more EPMS. Among those with only one EMPS, most frequent organ involvement included bone (40%), brain (32%), liver (13%) and adrenal (10%). Median overall survival (mOS) was worst in those with liver metastasis and best in those with adrenal metastasis (2.0 vs. 5.2 months, p=0.015). However, outcomes based on organ site involvement did not retain prognostic significance in multivariable analysis after controlling for other measured confounders. Compared to patients with one EPMS, individuals with ≥ 2 EPMS experienced worse outcomes (mOS 3.9 vs 2.9 months, p<0.001), and were associated with worse prognosis in Cox regression analysis (HR 1.5, 95%CI 1.3-1.7, p<0.001). A statistically and clinically significant inverse relationship persisted between increasing number of EMPS sites and mOS. Those patients who received systemic anti-cancer therapy or surgical resection of metastatic disease (received by 25% and 3% of total cohort respectively) demonstrated the most improved mOS, regardless of number or location of EMPS (10.0 vs 2.0 months, p<0.001, and 9.0 vs 3.0 months, p<0.001, respectively).
8eea62084ca7e541d918e823422bd82e Conclusion
We conclude that number, rather than location of EPMS is a prognostic factor in patients with stage IV M1b NSCLC. A simple count of metastatic sites at diagnosis may be of clinical value in in the management and advanced care planning for patients with metastatic NSCLC. Of note, this could assist in identification of patients who would benefit from either more aggressive treatment or best supportive care, and may be an important consideration in future clinical trial design. Overall, this study reinforces the need to advance efforts to determine and mitigate the factors predisposing patients to develop metastatic disease, and develop initiatives to reduce the number of patients presenting with advanced disease.
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P2.01-28 - Gender and Systemic Treatment Patterns: Impacts on the Overall Survival of Stage IV NSCLC 2010 – 2014 Diagnoses (ID 13368)
16:45 - 18:00 | Author(s): Gwyn Bebb
- Abstract
Background
Our previous work reports only ~25% systemic treatment uptake in stage IV non-small cell lung cancer (NSCLC) patients and proposed the availability of more tolerable regimen as one way of improving survival for NSCLC patients. The current study followed-up with the systemic treatment trend in stage IV NSCLC patients from 2010 to 2014, the era where effective and tolerable targeted agents such as EGFR- tyrosine kinase inhibitors (TKIs) and ALK inhibitors are available, to determine changes in clinical and treatment patterns impacting NSCLC survival over time.
a9ded1e5ce5d75814730bb4caaf49419 Method
Using the Glans-Look Lung Research (GLR) database, we defined the clinical features of stage IV NSCLC patients from 2010 to 2014, determined the impact of systemic treatment patterns and uptake rates on overall survival (OS).The findings were summarized with descriptive statistics (Fisher’s Exact tests) and Kaplan Meier survival curves using SPSS. Statistical significance was set at p value < 0.05 and 95% confidence intervals.
4c3880bb027f159e801041b1021e88e8 Result
Among the 470 patients diagnosed between the year 2010 – 2011, and 724 in 2012 – 2014, 26% and 33% received 1st line systemic treatment respectively. Overall, there was increased use of EGFR and ALK targets (18% in 2010 – 2011 versus 34% in 2012 – 2014 of all 1st line therapy) and a 13% decrease in platinum-based doublet (PBD) uptake over the years, (p = 0.001). This pattern of change was similar for patients ≤70 years versus >70 (p < 0.001). However, for female patients, PBD use remain constant despite the increased targeted agents uptake, (p = 0.001). The median OS was slightly better for female in the subsequent years, 7 (95% CI: 6 – 8) versus 4 (95% CI: 3 – 5) months, p = 0.036. In EGFR/ALK mutation positive patients who received 1st line TKIs, a non-statistically significant lower OS was observed in 2012 – 2014 compared to the previous years (p = 0.188). No significant difference in the OS between the year groups for patients with no actionable mutation treated with 1st line PBD (p = 0.393).
8eea62084ca7e541d918e823422bd82e Conclusion
In stage IV NSCLC, systemic treatment uptakes slightly increased with targeted agents, however this may not add up to overall survival benefits for the disease. Targeted agents may confer more benefits to female patients. Outcome results from multivariate analysis will be presented and discussed.
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P3.03 - Biology (Not CME Accredited Session) (ID 969)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.03-21 - CXCR4 Overexpression is Associated with Poor Survival Outcome After Recurrence in Early Stage Non-Small Cell Lung Cancer Patients (ID 13659)
12:00 - 13:30 | Author(s): Gwyn Bebb
- Abstract
Background
Overexpression of CXCR4 is associated with poor outcomes for patients with advanced non-small cell lung cancer (NSCLC). Studies suggest a gender specific difference in outcomes of stage IV NSCLC patients, with shorter survival in females with high expression of CXCR4. The current study evaluates the association between CXCR4 expression and gender, time to recurrence, and survival in early stage NSCLC patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patient characteristics, clinical variables and outcome data were obtained from the Glans-Look Lung Cancer database for stage I-III NSCLC patients diagnosed between 2003-2006 at the Tom Baker Cancer Centre. Tissue microarrays were created from surgical or biopsy specimens, and CXCR4 expression was evaluated using quantitative fluorescent immunohistochemistry. CXCR4 expression and outcome data were analyzed using a Cox proportional hazards and multi-state model.
4c3880bb027f159e801041b1021e88e8 Result
230 patients with stage I-III NSCLC were identified, and 181 patients had corresponding tissue for CXCR4 analysis. Early stage NSCLC patients with CXCR4 overexpression had worse overall survival compared to those with low CXCR4 expression (p<0.05). No gender specific difference was observed. Time to recurrence did not correlate with CXCR4 expression, and there was no association with the site of recurrence (local versus distant). However, high CXCR4 expression was associated with increased risk of death after recurrence (p<0.05).
8eea62084ca7e541d918e823422bd82e Conclusion
Early stage lung cancer patients with high CXCR4 expression have worse survival outcomes, particularly after recurrence of disease. The role of CXCR4 as a prognostic marker in NSCLC patients who have recurred should be further elucidated.
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P3.09 - Pathology (Not CME Accredited Session) (ID 975)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.09-16 - Transcriptome Profiling for Subtyping NSCLC: Off the Beaten Path(Ologist) (ID 13894)
12:00 - 13:30 | Author(s): Gwyn Bebb
- Abstract
Background
Histopathological distinction between non-small cell lung cancer subtypes is still relevant in the age of targeted therapy due to the relatively low number of patients with actionable molecular alterations such as EGFR mutations or ALK rearrangements in squamous cell carcinomas. In addition, for patients without these alterations, the choice of most effective chemotherapy regimens is often based upon non-squamous vs squamous cell histology. However, histopathology scoring typically requires resected or biopsied tissue to be fixed, sliced, stained, and subjectively scored by a pathologist. Here we endeavor to demonstrate that subtle variances in gene expression within NSCLC patient samples can be used to classify the cancer subtype with a high degree of accuracy to pathology classification.
a9ded1e5ce5d75814730bb4caaf49419 Method
RNA extracted from 46 resected NSCLC cases (34 stage IIA/B, 12 stage IIIA/B; primarily adenocarcinomas and squamous cell carcinomas) were profiled using a transcriptome microarray platform (Illumina) and analyzed and compared to normal tissue using several Bioconductor R package pathway analysis tools and DAVID Bioinformatics Resources 6.8. Expression profiles were grouped by principle component score in a blinded manner.
4c3880bb027f159e801041b1021e88e8 Result
Clustering samples based on the top 10% most variable genes resulted in a highly accurate separation of adenocarcinoma samples and squamous cell carcinoma samples, with only one case of squamous cell carcinoma being misclassified as adenocarcinoma. The altered pathways that differentiated these samples included p53 signalling and PI3K-Akt signaling pathways, Cell adhesion molecules (CAM), ECM-receptor interactions, Wnt signalling and several other key pathways.
8eea62084ca7e541d918e823422bd82e Conclusion
Due to the successes of targeted therapeutic approaches, evaluating patient biopsies or other samples for EFGR mutations and ALK rearrangements are currently the standard of care for advanced-stage NSCLC. Immunohistochemical staining for the purposes of subtyping NSCLC can aid in developing treatment strategies for patients without these molecular alterations, but this can significantly reduce the quantity of tissue available for subsequent molecular tests. Based on our data, we believe that expression variances in a relatively small pool of genes and pathway analysis is sufficient to accurately predict the subtype of NSCLC, or at least narrow the number of cases requiring input from a pathologist to a small number of more difficult cases.
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P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.13-10 - Factors Associated with Long-Term Survival of Stage IV NSCLC Patients on First-Line EGFR-Targeting Therapy (ID 12981)
12:00 - 13:30 | Author(s): Gwyn Bebb
- Abstract
Background
To determine factors associated with long term survival in Stage IV, non-small cell lung cancer (NSCLC) patients receiving EGFR-targeting agents (EGFR-TA) as systemic anti-cancer treatment in the first-line setting at a Canadian tertiary cancer centre.
a9ded1e5ce5d75814730bb4caaf49419 Method
Retrospective analysis was conducted on patients diagnosed with Stage IV (AJCC 7th edition) NSCLC between 1999 and 2014, and receiving EGFR-TA as first-line treatment. Demographic, clinical, histopathological, treatment and outcome data was extracted from the large, population-based institutional Glans-Look Lung Cancer Database. Long-term survivors (LTS) were defined as those surviving ≥ 18 months post EGFR-TA initiation. Correlates of survival were investigated via univariate analysis, Kaplan-Meier analysis using the log-rank test, and multivariate Cox regression.
4c3880bb027f159e801041b1021e88e8 Result
We identified 117 eligible patients. Median age was 65 (IQR 54.5-74) years, 61% female, 91% adenocarcinoma, 60% never smoking history, and 80% were identified as EGFR-mutant (remainder were untested and accessed EGFR-TA before routine testing was performed). Most common ethnicity (by place of birth) was North American (47%), followed by Asian (37%). 21% survived ≥ 18 months post-EGFR-TA initiation, with a median overall survival (mOS) of 46 vs. 13 months in those surviving < 18 months post-EGFR-TA initiation (p <0.001).
LTS were more likely to be over the age of 65 years at diagnosis (76% vs. 46%, p=0.012), receive palliative radiation therapy (72% vs. 27%, p<0.001), and possess Asian ethnicity (60% vs. 30%, p=0.044), although impact of age and radiation therapy did not retain prognostic significance in multivariate analysis after controlling for other measured confounders; Asian ethnicity was retained as a favorable prognostic factor for survival [HR: 0.5, 95%CI 0.3-0.8, p=0.005)]. Patients with Asian ethnicity revealed no significant demographic or clinical characteristics (notably gender, smoking status and EGFR mutation type) between LTS and non-LTS, with the exception of age. Asian LTS were significantly more likely to be ≥ 65 years of age at diagnosis (87% vs. 32%, p<0.001), a factor which retained significance as a favorable prognostic factor in multivariate analysis [HR: 0.3, 95% CI 0.2-0.7), p=0.004)].
8eea62084ca7e541d918e823422bd82e Conclusion
Analysis of this population-based cohort identifies Asian ethnicity, and within this ethnic group, older age at diagnosis, as favorable prognostic factors for patients with Stage IV, NSCLC accessing EGFR-TA in the first-line setting. These findings help identify patients who derive the most benefit from EGFR-TA, and suggest that older, Asian patients represent a unique sub-population within metastatic NSCLC, who may possess different biological underpinnings of NSCLC, outside of a propensity to harbor EGFR mutations.
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P3.13-28 - Heterogeneity, Prevalence and Prognostic Significance of PDL1 Expression in Early Resected NSCLC (ID 14335)
12:00 - 13:30 | Author(s): Gwyn Bebb
- Abstract
Background
The interaction between the programmed death protein-1 receptor (PD1) and its membrane-bound ligand (PDL1) is one mechanism by which tumor cells evade the immune system. Cancer immunotherapies target this interaction by blocking the function of either protein, allowing for T-cell activation and destruction of the tumor. Because PDL1 expression in tumor is used to identify patients who might benefit from immune-modulating treatment, its detection plays a key role in clinical recommendations. Our objectives are to assess the prevalence of PDL1 expression in early stage non-small cell lung cancer (NSCLC) patients, determine its association with clinical outcomes using the Glans-Look Research (GLR) database (Calgary, AB), and validate these findings using a cohort from the Manitoba Tumor Bank (MBTB).
a9ded1e5ce5d75814730bb4caaf49419 Method
A tissue microarray (TMA) was built using pre-treatment resected and biopsy tissue samples from 459 GLR database patients with early stage NSCLC, diagnosed between 2003 and 2010. Cell lines expressing varying levels of PDL1 were generated, embedded into HistoGel™ and co-mounted onto the GLR and MBTB arrays. Fluorescence immunohistochemistry was performed using anti-PDL1 E1L3N (Cell Signaling Technology), and PDL1 expression was evaluated as percent-positive and intensity scores in the cytoplasmic compartment of tumor and stromal cells using HALO™ automated image analysis software. Cell line PDL1 intensity scores served as on-slide reference standards to normalize PDL1 expression in patient specimens using R Programming software. PDL1-percent-positive tumor scores were generated to assess the cut-points of ≥50%(“PDL1-strong”), ≥1%-to-49%(“PDL1-weak”), and <1%(“PDL1-negative”), indicated by the FDA-approved companion diagnostic anti-PDL1 22C3 (Dako) for pembrolizumab. Clinicopathological outcomes were analyzed, and overall survival was assessed using the Kaplan-Meier method and compared using the log-rank test.
4c3880bb027f159e801041b1021e88e8 Result
Preliminary analyses indicate PDL1-weak/negative GLR patients with adenocarcinoma experienced higher median OS (3.50yrs) compared to PDL1-strong patients (1.91yrs) (p=0.0043). This trend was not significant over all histologies, or when using mean scores. The opposite trend was found with the MBTB cohort (2.52yrs vs. 1.76yrs OS, PDL1-strong vs. PDL1-weak/negative maximum scores, p=0.0410).
8eea62084ca7e541d918e823422bd82e Conclusion
Variations across datasets illustrate the difficulty in harmonizing PDL1 testing. Heterogeneity of protein expression, TMA sampling error, and differences between study cohorts can translate into variable correlations between PDL1-positivity and survival estimates. Increased survivorship in GLR adenocarcinoma patients with PDL1-weak/negative staining could challenge the notion of using PDL1 as a prognostic biomarker. Comparisons between the E1L3N and 22C3 anti-PDL1 assays will be performed, E1L3N percent-positive cut-points will be refined according to the lowest intensity-based statistical p-value, and further outcome findings will be presented and discussed.
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