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Desiree Hao
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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): Desiree Hao
- 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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MS19 - Pulmonary Dilemmas with Immunotherapy (ID 798)
- Event: WCLC 2018
- Type: Mini Symposium
- Track: Interventional Diagnostics/Pulmonology
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 201 BD
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MS19.01 - Drug-Induced Pneumonitis with IO: How worried should we be for our Lung Cancer Patients (ID 11481)
13:30 - 13:50 | Presenting Author(s): Desiree Hao
- 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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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.13-13 - Real-World Study of Osimertinib in EGFR T790M-Mutated Non-Small Cell Lung Cancer (NSCLC): ASTRIS Canadian Cohort Analysis (ID 12986)
16:45 - 18:00 | Author(s): Desiree Hao
- Abstract
Background
ASTRIS is an open-label, single-arm, multinational, real world study of osimertinib for patients with advanced/metastatic epidermal growth factor receptor-mutated (EGFRm) T790M-positive non-small cell lung cancer (NSCLC) who previously received therapy with an EGFR tyrosine kinase inhibitor (EGFR-TKI) (NCT02474355). Data cut-off (DCO) for the second interim analysis was 20 October 2017, with 3014 patients enrolled (full analysis set), including 99 patients in Canada.
a9ded1e5ce5d75814730bb4caaf49419 Method
Adult patients with locally advanced/metastatic EGFRm NSCLC, not amenable to curative surgery/radiotherapy, with confirmation of T790M and prior EGFR-TKI therapy were enrolled. Patients were included with World Health Organization performance status of 0 to 2, as well as those with asymptomatic stable central nervous system (CNS) metastases. Patients received osimertinib 80 mg once daily until loss of clinical benefit. The primary efficacy outcome was overall survival (OS), with secondary outcomes of investigator-assessed response rate (RR), progression-free survival (PFS), and time to treatment discontinuation (TTD).
4c3880bb027f159e801041b1021e88e8 Result
From study start (14 January 2016) to DCO (20 October 2017), 99 patients were enrolled at 12 Canadian centres. Median age was 64 years (30-89 years). Patients were 68% female, 57% Asian, and had ECOG 0/1/2 of 22%/65%/13%. Twenty-five patients had CNS metastases at screening. Gefitinib was the most commonly used previous EGFR-TKI (gefitinib, erlotinib and afatinib were 80%, 14%, and 14%, respectively). Thirty-nine percent had previous chemotherapy; 6% previous immunotherapy; 46% previous radiotherapy. All patients had T790M: 75% tissue, 7% blood and 18% cytology. Biomarker testing methods varied, with the majority (61%) identified by Entrogen EGFR kit. At DCO, 45 patients had discontinued treatment. OS data were immature. Median PFS was 11.0 months (95% CI, 8.9-13.3). Median TTD was 14.9 months (95% CI, 11.2-not calculated). RR was 67.0% (95% CI, 56.7-76.2); sub-analyses showed RR of 69.9% (58.0-80.1), 66.7% (22.3, 95.7) and 55.6% (30.8, 78.5) for patients with T790M by tissue, blood and cytology, respectively. Serious adverse events (AEs) were reported for 18% of patients. AEs leading to dose modifications and discontinuations were reported for 12% and 5% of patients, respectively.
8eea62084ca7e541d918e823422bd82e Conclusion
The Canadian results from this real world study of osimertinib in advanced/metastatic EGFRm T790M-positive NSCLC, which includes heavily pretreated patients and various approaches to biomarker testing, were comparable to outcomes reported in the phase III study AURA3 (NCT02151981). These findings provide further support for osimertinib as standard of care for EGFRm T790M-positive NSCLC.
6f8b794f3246b0c1e1780bb4d4d5dc53
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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): Desiree Hao
- 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.
6f8b794f3246b0c1e1780bb4d4d5dc53
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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: 1
- 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): Desiree Hao
- 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.
6f8b794f3246b0c1e1780bb4d4d5dc53
