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Randeep Sangha



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    EX04 - Mini Oral Abstract Session - MA08.06, MA18.02, MA19.02, MA20.11 (ID 1006)

    • Event: WCLC 2018
    • Type: Exhibit Showcase
    • Track: Advanced NSCLC
    • Presentations: 1
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      EX04.02 - The Impact of Treatment Evolution in NSCLC (iTEN) Model: Development and Validation (ID 13468)

      10:00 - 10:05  |  Author(s): Randeep Sangha

      • Abstract
      • Slides

      Background

      Background: The iTEN model was developed to estimate the survival impact of new treatments for advanced NSCLC (aNSCLC) patients. The structure and key assumptions of the iTEN model and outputs validated against published real-world survival data are presented.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Methods: The iTEN model is a discrete event simulation of aNSCLC patients’ treatment plans. Individual patient characteristics (histology, molecular subtypes (EGFR, ALK, ROS1, BRAF, PD-L1), and performance status) are generated by random sampling from Canadian prevalence estimates. All Health Canada approved agents for treatment of aNSCLC are included. Simulated patients start on first-line therapy and move to subsequent lines of therapy in modelled progression events. Up to six-lines of therapy can be included. Time-of-event for progression or death for each patient is calculated based on random probabilities and progression-free survival (PFS) and overall survival (OS) curves modelled from published clinical trials. For example, a simulated ALK+ patient might receive first-line crizotinib, followed by second-line ceritinib and BSC, based on PFS/OS data from PROFILE 1014 and ASCEND-5. Predicted OS is calculated as the cumulative time spent on active therapy and BSC. PFS/OS data were extrapolated using best practices. Treatment on previous therapies was assumed to have no impact on the efficacy of subsequent therapies. Model survival predictions were validated against published real-world estimates from the Ontario Cancer and Austrian (TYROL) registries, by reproducing the same treatment mix in the simulated patients as in the publications.

      4c3880bb027f159e801041b1021e88e8 Result

      Results: iTEN estimated two- to five-year survival rates were similar to those reported by the Ontario Cancer and TYROL registries.

      abstract1 image.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      Conclusions: While further analyses are required, the iTEN model produces survival estimates comparable to published real-world data; therefore, the iTEN model may be a valid tool to estimate aNSCLC patient survival.

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    OA05 - Clinical Trials in IO (ID 899)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 106
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      OA05.06 - CheckMate 227: Patient-Reported Outcomes of First-Line Nivolumab + Ipilimumab in High Tumor Mutational Burden Advanced NSCLC (ID 13450)

      14:25 - 14:35  |  Author(s): Randeep Sangha

      • Abstract
      • Presentation
      • Slides

      Background

      The randomized, open-label, multipart phase 3 study CheckMate 227 (NCT02477826) demonstrated a significant progression-free survival benefit (co-primary endpoint) with first-line nivolumab+ipilimumab versus histology-based, platinum-doublet chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and high tumor mutational burden (TMB; ≥10 mutations/Mb). Patient-reported outcomes (PROs) for this population within CheckMate 227 are presented.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Eligible chemotherapy-naïve patients had stage IV or recurrent NSCLC, ECOG performance status 0−1, and no known sensitizing EGFR/ALK alterations. PROs were assessed as an exploratory endpoint; this analysis included patients with high TMB randomized to nivolumab+ipilimumab or chemotherapy; specific outcomes included proportion of patients with disease-related symptom deterioration by 12 weeks and time to deterioration in symptoms (by Lung Cancer Symptom Scale [LCSS] Average Symptom Burden Index [ASBI]), and assessment of quality of life and overall health status (by EuroQoL-5 Dimension [EQ-5D] utility index [UI] and visual analog scale [VAS]). PROs were evaluated each cycle (Q2W, nivolumab+ipilimumab; Q3W, chemotherapy) for the first 6 months, every 6 weeks thereafter during treatment, and at follow-up visits 1/2. EQ-5D was also assessed during survival follow-up.

      4c3880bb027f159e801041b1021e88e8 Result

      PRO completion rates were ~90% at baseline and >80% for nearly all on-treatment assessments. Among patients with high TMB, fewer patients in the nivolumab+ipilimumab (n=139) versus chemotherapy (n=160) groups reported symptom deterioration by week 12, irrespective of whether they were still on therapy or had discontinued (22.3% versus 35.0%; absolute risk reduction: 12.7% [95% CI: 2.4–22.5]). Time to first deterioration (TTD) using common assessment time points (on/off treatment) was delayed with nivolumab+ipilimumab versus chemotherapy for the LCSS ASBI (hazard ratio [HR]: 0.40; 95% CI: 0.26–0.63) and 3-Item Global Index (3-IGI; HR: 0.56; 95% CI: 0.38–0.82). The estimated benefit in TTD generally favored nivolumab+ipilimumab for individual symptoms in the ASBI and each item in the 3-IGI (HRs: 0.48–0.74), except for hemoptysis (HR: 1.20), which exhibited very low burden; an advantage for nivolumab+ipilimumab was also seen in the EQ-5D VAS (HR: 0.62; 95% CI: 0.42–0.92) and UI (HR: 0.50; 95% CI: 0.34–0.73). Mean changes from baseline with nivolumab+ipilimumab showed early and clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; for patients treated with chemotherapy, symptoms and quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following completion of chemotherapy (EQ-5D VAS).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Nivolumab+ipilimumab demonstrated early and sustained improvements in health-related quality of life versus chemotherapy in patients with advanced NSCLC and high TMB.

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    P2.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 964)

    • 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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      P2.15-09 - The Impact of Treatment Evolution in NSCLC (iTEN) Model: Survival and Cost of Treating Patients with Advanced NSCLC in 2017 (ID 13477)

      16:45 - 18:00  |  Author(s): Randeep Sangha

      • Abstract
      • Slides

      Background

      Background: The life expectancy and healthcare costs of treating advanced NSCLC (aNSCLC) patients are expected to rise as new targeted and immuno-oncology (IO) therapies are approved for clinical practice. Here, we have used the iTEN model to estimate the cost of managing aNSCLC patients in Canada in 2017.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Methods: The iTEN model development and validation are presented in an accompanying abstract (“The iTEN model: Development and Validation”). A treatment algorithm for EGFRm, T790m, ALK re-arrangement and PD-L1+ aNSCLC patients in 2017 was generated through a modified Delphi process based on anonymous responses from Canadian clinical experts. The generated treatment algorithm was used to estimate the survival and life-time costs of managing patients. Health resource use and cost estimates included drug acquisition and administration, adverse events, laboratory and radiologic monitoring, physician visits and end of life costs (2018 costs). Cost estimates were based on published literature, Ontario formulary listings, Cancer Care Ontario recommendations and the Ontario Case Costing Initiative. The estimation of survival is described in the companion abstract.

      4c3880bb027f159e801041b1021e88e8 Result

      Results: Survey responses indicated that first-line therapy is consistent with current guideline recommended practice, but that care beyond the second-line is variable, particularly with respect to IO usage. Modelled life expectancy varied based on the molecular subtype of aNSCLC. Costs over the span of an average aNSCLC patient’s life-time were estimated to be $89,899 (range: $61,134-$194,158). In comparison, the life-time cost of treating a Canadian lung cancer patient in 2007 (ie, prior to the introduction of IOs and ALK TKIs), inflated to 2018 dollars, was an estimated $60,678 (de Oliveira et al., 2016).

      abstract2 image - corrected.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      Conclusions: Results suggest that aNSCLC patient survival increases in conjunction with increased expenditure. The iTEN model may be used to assess the impacts of evolving treatment paradigms in aNSCLC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 966)

    • 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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      P2.17-28 - Real-World Data: Survival Outcomes of Chemotherapy Regimens Given Concurrently with Radiotherapy for Locally Advanced NSCLC (ID 12013)

      16:45 - 18:00  |  Author(s): Randeep Sangha

      • Abstract
      • Slides

      Background

      Initial management for inoperable Stage III non-small cell lung cancer (NSCLC) treated for curative intent is platinum-based chemotherapy with concurrent thoracic radiotherapy (TRT). However, a lack of consensus on the optimal chemotherapy regimen administered with TRT remains. In Alberta, Canada, cisplatin/etoposide (EP), given Days 1-5 + 8 of a 28-day cycle, and cisplatin/vinorelbine (VP), given Days 1 +8 of a 21-day cycle, have been the two regimens used preferentially. Weekly carboplatin/paclitaxel (CP) has historically been used as an alternative in patients (pts) with borderline performance status or contraindication to cisplatin. Here, we retrospectively compare survival outcomes of these chemotherapy regimens.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The Alberta Cancer Registry identified pts diagnosed with locally advanced NSCLC between 2010 and 2015 and treated with EP, VP or CP chemotherapy with concurrent TRT. Patient and tumour characteristics were collected along with treatment parameters. Progression-free survival (PFS) and overal survival (OS) was determined for each chemotherapy regimen. Survival outcomes were compared using Kaplan-Meier analysis and Cox proportional hazard regression models adjusting for age, gender, tumour histological subtype (squamous vs. non-squamous NSCLC) and 7th edition TNM Stage (IIIA vs. IIIB).

      4c3880bb027f159e801041b1021e88e8 Result

      Of 148 pts reviewed, 44, 79, and 25 pts were treated with EP, VP, and CP, respectively, with median ages of 63, 62, and 68 years. Gender, tumour histological subtype, distribution of Stage IIIA vs. IIIB, and use of PET imaging for staging were balanced between regimens. Median PFS (EP 9.5 mo; VP 12.9 mo; CP 11.2 mo; p=0.875) and OS (EP 17.8 mo; VP 25.3 mo; CP 33.2 mo; p=0.509) were not significantly affected. Non-squamous median OS (EP 33.4 mo; VP 31.0 mo; CP 33.2 mo; p=0.997) and squamous median OS (EP 13.4 mo; VP 22.3 mo; CP not reached (N=11); p=0.406) also did not differ by regimen. Multivariate Cox regression analysis demonstrated Stage (IIIA vs. IIIB) as the only parameter that significantly altered PFS and OS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This retrospective analysis of real-word data from 2010 to 2015, in the absence of consolidation durvalumab, shows that PFS and OS in locally advanced NSCLC pts treated with concurrent chemoradiotherapy are similar for the EP, VP or CP regimens. Dose scheduling and respective toxicities will likely determine choice of chemotherapy regimen given with TRT. Further review of the CP regimen, given the small sample size in this study, and the use of next generation chemotherapy regimens such as platinum/pemetrexed for non-squamous NSCLC is warranted.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)

    • 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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      P3.04-17 - Cost-Effectiveness of Atezolizumab for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) in Canada (ID 13497)

      12:00 - 13:30  |  Author(s): Randeep Sangha

      • Abstract
      • Slides

      Background

      Atezolizumab is a humanized monoclonal antibody targeting PD-L1 that enhances tumour-specific T-lymphocyte responses. The efficacy and safety of atezolizumab versus docetaxel was demonstrated in patients with advanced NSCLC previously treated with chemotherapy in the phase III OAK trial (NCT02008227). Here, we report the cost-effectiveness in Canada of atezolizumab compared with docetaxel and nivolumab in previously-treated advanced NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A cost-utility analysis was performed to estimate the cost per quality-adjusted life-year (QALY) associated with atezolizumab treatment compared to docetaxel and nivolumab in previously-treated advanced NSCLC. A three-state partitioned-survival model was developed, and the target population reflected patients in the OAK study. The analysis was conducted using a 10-year time horizon from the perspective of the Canadian publicly-funded healthcare system. Treatment efficacy was informed by the OAK trial (data cut-off date of January 23, 2017), with crossover adjustment. Overall survival (OS), progression-free survival (PFS), and time to treatment discontinuation (TTD) for atezolizumab were estimated by parametric extrapolation of Kaplan-Meier (KM) data from OAK. For OS, a cure modelling approach was used with an assumed cure fraction of 1% for atezolizumab to represent long-term survivorship as seen with cancer immunotherapy. OS, PFS and TTD for docetaxel and nivolumab were estimated through network meta-analysis of randomized controlled trials. A discount rate of 1.5% was applied in the base case to costs and effects. Costs considered in the analysis included treatments and administration, supportive care, adverse events management, subsequent treatments, and terminal care. Most costs were obtained from publicly-available sources. Health-related quality of life was estimated using EQ-5D-3L data from OAK. All analyses were performed probabilistically, and several scenario analyses were performed to assess the robustness of results.

      4c3880bb027f159e801041b1021e88e8 Result

      The base-case incremental cost per QALY for atezolizumab versus docetaxel was $142,074 (2017 CAD). Atezolizumab resulted in more QALYs and less costs compared to nivolumab; however, differences were small. Docetaxel had the highest probability of being cost effective at a willingness-to-pay (WTP) threshold below $125,000/QALY; the probability that atezolizumab was cost effective approached 40% at WTP thresholds beyond $125,000/QALY. Results were generally consistent in scenario analyses.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The ICER of atezolizumab vs. docetaxel used as second-line treatment for advanced NSCLC was $142,074/QALY. Atezolizumab dominated nivolumab; however, differences were small. The results of our analysis, as well as the added convenience of a fixed-dose regimen administered every three weeks, support the use of atezolizumab for patients in Canada with advanced NSCLC after progression on chemotherapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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