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Adrian Sacher



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    MA15 - Colliding Approaches - EGFR and Immunotherapy (ID 916)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 13:30 - 15:00, Room 107
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      MA15.04 - Discussant - MA 15.01, MA 15.02, MA 15.03 (Now Available) (ID 14641)

      13:45 - 14:00  |  Presenting Author(s): Adrian Sacher

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MA18 - Modelling, Decision-Making and Population-Based Outcomes (ID 920)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 13:30 - 15:00, Room 201 F
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      MA18.07 - Awareness of the Harms of Continued Smoking Among Lung Cancer (LC) Survivors (Now Available) (ID 12024)

      14:05 - 14:10  |  Author(s): Adrian Sacher

      • Abstract
      • Presentation
      • Slides

      Background

      Continued smoking after a LC diagnosis is associated with poorer cancer outcomes including increased risk of treatment-related side-effects, reduced treatment efficacy and poorer prognosis. Smoking cessation is an integral part of LC survivorship by improving both cancer and non-cancer outcomes. To enhance survivorship education, clinicians should understand patient awareness of the harms of continued smoking.

      Method

      LC survivors from Princess Margaret Cancer Centre, Toronto (2014-2017) were surveyed with respect to self-awareness of the harms of continued smoking on cancer-related outcomes. Univariable and multivariable logistic regression models assessed factors associated with awareness and whether awareness was associated with cessation among current smokers at diagnosis.

      Result

      Of 553 patients, 181 were lifetime never-smokers. Among those smoking during the peri-diagnosis period (n=177), 65% quit after diagnosis. Among all, few patients were aware that smoking negatively impacts treatment-related outcomes [complications from cancer surgery (only 41% aware), radiation side-effects (30%), quality-of-life on chemotherapy (44%) and treatment efficacy (36%)]; half were aware that smoking negatively impacts cancer prognosis (51% aware) and risk of developing second primaries (50%). Compared to ex-smokers/never-smokers at diagnosis, current smokers at diagnosis were less aware of the impact of smoking on radiation side-effects (22% vs 31% aware, P=0.01), prognosis (44% vs 55%, P=0.02) and risk of second primaries (42% vs 55%, P=0.007). Among sociodemographic variables, only those speaking English at home were consistently found more likely unaware that smoking negatively impacts these outcomes (ORs=1.52-2.20, P<0.04). Patients with early stage disease were more likely unaware that smoking negative impacts radiation side-effects (OR=1.60, 95%CI[1.09-2.35], P=0.02); while patients on curative treatment (OR=1.53[1.08-2.17], P=0.02) and those exposed to second-hand smoke (SHS) were more likely unaware that smoking impacts quality-of-life on chemotherapy (OR=1.64[1.05-2.58], P=0.03). Exposure to SHS, treatment intent and stage were not associated with awareness of impact on prognosis or second primaries (P>0.11). Among smokers in the peri-diagnosis period, awareness of the impact of smoking on surgical complications (aOR=2.09 [0.96-4.54], P=0.06), quality-of-life while receiving chemotherapy (aOR=2.60[1.17-5.79], P=0.02) and on treatment efficacy (aOR =2.24[0.97-5.20], P=0.06) were each associated with subsequent quitting, adjusted for marital status, pack-years, self-rated health and SHS exposure.

      Conclusion

      Many LC patients are unaware of the harms of continued smoking on cancer outcomes, particularly those smoking at diagnosis. Awareness of some of these outcomes was associated with subsequent tobacco cessation. Patient education on the health benefits of smoking cessation may increase quit rates and improve outcomes for LC patients.

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    MTE18 - Case-Based Management of Patients with Inadequate Tissue for Molecular Tests (Ticketed Session) (ID 828)

    • Event: WCLC 2018
    • Type: Meet the Expert Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 07:00 - 08:00, Room 201 F
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      MTE18.01 - Case-Based Management of Patients with Inadequate Tissue for Molecular Tests (Now Available) (ID 11577)

      07:00 - 08:00  |  Presenting Author(s): Adrian Sacher

      • Abstract
      • Presentation
      • Slides

      Abstract

      Plasma genotyping has rapidly evolved from an investigational technology into a standard-of-care tool with the potential to direct therapy in metastatic non-small cell lung cancer (NSCLC). Tissue genotyping has historically been considered the gold standard for genotyping in NSCLC both at initial diagnosis and acquired resistance to therapy. However, plasma genotyping is increasingly useful as a rapid alternative to tissue genotyping in certain clinical contexts. This technology is particularly applicable in patients with insufficient tissue available for genotyping at initial diagnosis as well as at the development of acquired resistance. The optimal use and interpretation of plasma genotyping requires understanding of cell-free DNA (cfDNA) biology, assay characteristics and the application of testing in different clinical scenarios.

      In newly diagnosed metastatic NSCLC, plasma genotyping is useful for the detection of targetable genomic alterations or non-targetable driver alterations (eg, KRAS) that are mutually exclusive with targetable alterations. The potential utility of plasma genotyping in newly diagnosed patients is particularly pronounced in patients with insufficient tissue from their diagnostic biopsies for genotyping, those with inaccessible or difficult to biopsy lesions and patients in which rapid initiation of treatment is needed due to clinical deterioration. The high positive predictive value of most modern plasma genotyping platforms for the detection of targetable genomic alterations means that positive results can be used to rapidly guide initial targeted therapy in metastatic NSCLC patients. However, the modest sensitivity of these assays requires that negative results be confirmed by tissue genotyping with repeat biopsy, if necessary.

      In patients with acquired resistance to targeted therapy, plasma genotyping can be utilized to detect resistance mutations at the time of progression. Furthermore, plasma genotyping may detect resistance mutations missed by standard tissue genotyping in this context due to tumor heterogeneity. Plasma T790M testing in patients with acquired resistance to first- and second-generation EGFR kinase inhibitors has been utilized extensively for selecting patients for treatment with second-line osimertinib. However, the utility of this technology in acquired resistance to EGFR therapy is likely to decrease as more patients are treated with front-line osimertinib without a targeted therapy option at development of acquired resistance. The recent explosion of multiple treatments for ALK acquired resistance has opened a new opportunity to apply plasma genotyping technology for the selection of second-line targeted therapy in these patients.

      While cfDNA technology has aided in the detection of actionable mutations, there remain challenges at present related to modest assay sensitivity, standardization of both analytic and clinical validation across testing platforms and adapting this technology to the ever-changing treatment landscape of metastatic NSCLC. In addition, DNA captured in plasma may be from multiple sources other than tumor, including germline, fetal, post-organ transplantation and clonal hematopoiesis of indeterminate potential (CHiP). These mixed sources have been routinely detected in commercial-based assays and can affect the interpretability of assay results.

      Despite potential limitations, cfDNA platforms offer immense promise in serving as an accurate molecular proxy for tumor biology. There is considerable potential for plasma genotyping in the detection of early-stage disease and for patients at risk for disease recurrence post curative intent therapy. In addition, there may be future utility with these assays in the detection of tumor mutational burden (TMB) and other predictive biomarkers of immunotherapy. Future prospective efforts that mandate plasma interrogation both as a static and dynamic biomarker will enable a firmer understanding of how best to utilize this unique technology.

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    P2.03 - Biology (Not CME Accredited Session) (ID 952)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.03-03 - Upfront Next Generation Sequencing in NSCLC: A Publicly Funded Perspective (Now Available) (ID 11826)

      16:45 - 18:00  |  Author(s): Adrian Sacher

      • Abstract
      • Slides

      Background

      A growing number of targeted drug treatments in non-small cell lung cancer (NSCLC) have led to the need for molecular profiling beyond the standard of care (SOC) EGFR/ALK. Here we present actionable targets, impact on patient treatment, clinical trial opportunities and costs using the Illumina TruSight Tumor 15 panel (TST15) for NSCLC samples.

      Method

      Tissue-based next generation sequencing using the TST15 was reflexively performed on all newly diagnosed cases of non-squamous NSCLC at the University Health Network (Toronto, Canada) from February 2017-February 2018. The panel identifies hot spot mutations in KRAS, EGFR, TP53, PIK3CA, BRAF, ERBB2, FOXL2, GNA11, GNAQ, KIT, NRAS, PDGFRA, RET, AKT1 and MET, but not fusions, copy number variations (CNV) nor MET exon 14 skipping mutations. Patient age, stage, pathologic subtype, and genotyping results were collected prospectively. Treatment changes as a result of TST15 and clinical trial opportunities (clinicaltrials.gov) were identified. Incremental testing costs were based on direct laboratory costs, but not personnel and administration costs.

      Result

      Testing included 342 samples from 336 patients. The TST15 panel identified 409 mutations from 342 samples. Sample demographics include: male: 53, and stage 1/2/3/4: 34/8/15/43%. Incremental actionable targets beyond EGFR and ALK were identified in 3.5% of patients (ERBB2 2.3%, BRAF V600E 1.2%). Most mutations occurred in TP53 (43%), EGFR (24%) and KRAS (26%). Co-mutations occurred in 32% (TP53, KRAS, EGFR) of samples. To date, one patient has had a treatment change as a result of TST15 beyond targeting EGFR. Above SOC clinical trial options were identified for 88% of stage IV and 26% of stage III patients. 3.6 samples were needed to identify one actionable mutation, predominantly in EGFR, at an estimated cost of $1919 CAD per target.

      Conclusion

      Extended genotyping with TST15 in NSCLC identifies an additional 3.5% of patients with actionable mutations above SOC and improves clinical trial options for patients. Despite this, impact on patient treatment beyond targeting EGFR is minimal. To enhance the number of targets and minimize costs, affordable population-based comprehensive testing with a panel that includes fusions/CNV is needed.

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      P2.03-04 - Next Generation Sequencing in Lung Cancer Using the Oncomine Comprehensive Assay: The Canadian Publicly Funded Experience (Now Available) (ID 12181)

      16:45 - 18:00  |  Author(s): Adrian Sacher

      • Abstract
      • Slides

      Background

      Standard of care (SOC) diagnostics for patients with stage IV non-small cell lung cancer (NSCLC) in Canada includes EGFR and ALK testing. Other genomic alterations are not tested routinely; however, access to enhanced molecular testing may broaden treatment options, clinical trial access, and improve outcomes for patients. This study uses the Oncomine Comprehensive Assay (OCA) v3, a next generation sequencing (NGS) panel in NSCLC to evaluate actionable targets, clinical trial eligibility, treatment impact, costs, turnaround time, and patient preference.

      Method

      Consecutive consenting stage IV NSCLC outpatients at the Princess Margaret Cancer Centre without EGFR/ALK/KRAS/BRAF derangement diagnosed at the University Health Network (UHN) in Toronto, Canada will be enrolled to undergo OCA testing on diagnostic samples. The selected platform (OCA v3, ThermoFisher) includes 161 genes including hotspots, fusions, and copy number variations. Patient age, pathologic subtype, genotyping results and treatment history will be collected. Primary endpoints include incremental actionable targets identified and clinical trial opportunities (clinicaltrials.gov) added through incremental testing beyond SOC. Secondary endpoints include treatment changes as a result of OCA testing, costs from the perspective of the Canadian public healthcare system, patient willingness-to pay, and test turnaround time.

      Result

      The study activated in February 2018 with 7 patients enrolled as of April 2018. Results of the value of incremental OCA testing beyond standard of care in the Canadian public healthcare system will be presented at the meeting.

      Conclusion

      While OCA testing in patients with advanced NSCLC may identify more actionable targets than selected genotyping, its cost effectiveness in the Canadian healthcare system is unknown and will be determined through this study.

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