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K.M. Wong



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    MO08 - NSCLC - Early Stage (ID 117)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO08.08 - A cost-effectiveness analysis of the 15-gene expression signature in guiding adjuvant chemotherapy in early stage non-small cell lung cancer based on the JBR.10 trial (ID 1962)

      16:15 - 17:45  |  Author(s): K.M. Wong

      • Abstract
      • Presentation
      • Slides

      Background
      The NCIC CTG JBR.10 trial demonstrated that adjuvant chemotherapy (ACT) improves survival in resected stage IB/II non-small cell lung cancer (NSCLC) compared to observation. A 15-gene expression signature was developed from the trial population and subsequently validated to stratify patients with resected NSCLC into low and high risk prognostic groups. The signature may also be predictive for greater benefit from ACT in high risk patients (Zhu et al. JCO 2010), but this has not yet been validated. This gene expression signature may offer a risk stratification strategy to identify patients most likely to benefit from ACT. We conducted an exploratory economic analysis to assess the impact of the use of this gene signature compared to current clinical staging to guide ACT decisions in resected early stage NSCLC.

      Methods
      We developed a decision analytic model populated by the NCIC CTG JBR.10 trial cost and outcome data, including direct medical costs and overall survival (OS). Utility for each health state was estimated from quality of life data to generate quality-adjusted survival. The analysis was performed over a lifetime horizon from the perspective of the Canadian public health care system, expressed in 2013 Canadian dollars. Survival and costs were discounted at 5% per year. We determined the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) of ACT versus observation in resected stage IB/II NSCLC in the following two scenarios: (1) gene signature-directed ACT, where patients classified as having high risk of recurrence receive ACT and those at low risk are observed; and (2) clinical stage-directed ACT, where gene signature profiling is not performed – those with stage IB tumours >4cm or stage II NSCLC receive ACT, and those with stage IB tumours <4cm are observed. Nonparametric bootstrapping to estimate 95% confidence intervals (CI) and multi-way sensitivity analyses were performed.

      Results
      The analysis included 52 patients in the gene signature-based strategy and 125 patients in the stage-based strategy with available direct medical costs and gene signature data. The mean survival gain of ACT versus observation was 2.28 years using gene signature-directed selection, and 1.59 years using stage-directed selection. The discounted ICER of ACT versus observation was $8,327/life-year gained (LYG; 95% CI, $395 to $19,590) using the gene signature-directed approach, and $5,623/LYG (95% CI, -$2,161 to $14,354) for the clinical approach. There was no significant difference in the ICER between the two strategies (p=0.52). The discounted ICUR was $11,315/quality-adjusted life-year (QALY; 95% CI, $211 to $27,314) using the gene signature-directed approach, and $7,728/QALY (95% CI, -$3,080 to $19,825) for the clinical approach. Sensitivity analyses showed that the ICER was most sensitive to changes in the survival hazard ratio (i.e. treatment benefit) and utility, but less sensitive to the cost of the gene signature (range $0 to $10,000 per case, with corresponding ICER $15,794 to $28,194/LYG, respectively).

      Conclusion
      This exploratory analysis suggests that use of the 15-gene expression signature to guide decisions for ACT in resected stage IB/II NSCLC patients could be highly cost-effective. Further validation of the signature’s impact on ACT outcomes is needed.

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    O24 - Cancer Control and Epidemiology III (ID 134)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      O24.05 - The impact of body mass index on survival in stage 3 and 4 lung cancer (ID 663)

      16:15 - 17:45  |  Author(s): K.M. Wong

      • Abstract
      • Presentation
      • Slides

      Background
      Obesity has been shown to be an adverse prognostic factor in several cancers, including breast, colorectal, endometrial, ovarian, pancreatic and prostate. However, studies of body mass index (BMI) and outcomes in lung cancer are lacking. Understanding the clinical impact of body weight on cancer outcomes is important given the high prevalence of obesity globally. We retrospectively evaluated the distribution of BMI at diagnosis and its effects on survival in stage 3 and 4 lung cancer patients.

      Methods
      1,121 patients with stage 3 or 4 lung cancer from a single institution were analyzed. Clinicopathologic data were collected retrospectively. Adjusted hazard ratios (aHR) for overall survival (OS) and progression-free survival (PFS) were generated by Cox regression for each BMI (kg/m[2]) category (underweight: <18.5, normal: 18.5-24.9, overweight: 25.0-29.9, obese: ≥30), after adjusting for age, gender, Charlson Comorbidity Index, performance status (PS), clinical stage and treatment regimen.

      Results
      In this cohort (n=1,121), the frequencies of stage 3A, 3B and 4 lung cancers were 35%, 32% and 33%, respectively. There were 633 (57%) adenocarcinomas, 238 (21%) squamous cell carcinomas, 38 (3%) small cell lung cancers, and 210 (19%) other histologies. Patients had variable BMI: 82 (7%) underweight, 550 (49%) normal weight, 333 (30%) overweight, 156 (14%) obese. Being overweight/obese was associated with older age (p=0.002) and stage 3A disease (p=0.001); underweight patients were more likely current smokers (p<0.001). OS was significantly decreased with age ≥65, males, PS 2-3, stage 4, and lack of systemic treatment (p<0.001). Median OS in underweight, normal weight, overweight and obese patients were 14, 23, 24 and 26 months, respectively. Compared with BMI ≥18.5, being underweight was associated with significantly poorer OS (aHR 1.33, 95% CI 1.01-1.77, p=0.045), but not PFS (aHR 1.12, 95% CI 0.86-1.46, p=0.414). The magnitude of this association was greatest among those aged less than 65 years (aHR 1.57, 95% CI 1.11-2.22, p=0.011).

      Conclusion
      In stage 3 and 4 lung cancer, being underweight at diagnosis is associated with significantly poorer OS, especially in patients younger than 65 years of age. Lower BMI is mostly observed in current smokers, while above normal BMI is seen in older patients and stage 3A disease. Unlike other malignancies, obesity does not increase mortality in this population. The BMI-survival relationship in lung cancer requires further study.

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    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.11-003 - The use of epidermal growth factor receptor tyrosine kinase inhibitors in treatment of advanced EGFR wild-type non-small cell lung cancer: a meta-analysis study (ID 657)

      09:30 - 16:30  |  Author(s): K.M. Wong

      • Abstract

      Background
      The epidermal growth factor receptor (EGFR) oral tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, improve progression-free survival (PFS) compared to chemotherapy in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) with activating EGFR mutation. Previous trials of TKIs in unselected patients suggest that they may have some activity in EGFR wild-type (WT) patients, but the magnitude of benefit is unclear. We conducted a meta-analysis to determine the outcomes of EGFR WT patients with advanced NSCLC treated with gefitinib or erlotinib.

      Methods
      MEDLINE was searched for phase 2 and 3 clinical trials of gefitinib or erlotinib in advanced NSCLC published between January 2000 and May 2012. Trials using TKI as treatment arm (i.e. compared against placebo or chemotherapy), control arm or maintenance therapy were included. In addition, studies must have tested for EGFR mutation by polymerase chain reaction and analyzed EGFR WT patients. Random effects meta-analysis using the DerSimonian and Laird method was performed to pool survival estimates (hazard ratios (HR), risk ratios) and objective response rate (ORR). Placebo- and chemotherapy-controlled phase 3 trials were evaluated separately in a subgroup analysis.

      Results
      Six randomized controlled trials (RCTs) with a total of 1,180 EGFR WT patients (709 on TKI, 471 on control with placebo or chemotherapy) were available for meta-analysis. Pooled overall survival (OS) from 5 RCTs was not significantly different for patients in the TKI arm compared to control arm (HR 1.00; 95% CI 0.86-1.16). Subgroup analysis according to type of control showed that TKI offered no OS benefit compared to either placebo (HR 0.92, 95% CI 0.63-1.35) or chemotherapy (HR 1.02, 95% CI 0.86-1.22) (interaction p=0.63). Likewise, pooled PFS was similar between TKI and control in 4 RCTs (HR 1.35; 95% CI 0.79-2.31). However, the use of TKI significantly increased PFS compared to placebo (HR 0.78, 95% CI 0.63-0.97), but not compared to chemotherapy (HR 1.64, 95% CI 0.96-2.79) (interaction p=0.01). The rate of patients in the control arm who subsequently received TKI upon progression ranged from 3% to 52%. ORR estimated from 51 studies (1,872 EGFR WT patients) was 8.4% (95% CI 6.0-10.8), and was similar for gefitinib and erlotinib. Sensitivity analysis removing studies with estimated effect sizes did not affect these findings.

      Conclusion
      In this meta-analysis, gefitinib and erlotinib significantly increase PFS compared to best supportive care for advanced NSCLC with EGFR WT status. The lack of OS gain may be explained by significant crossover in these trials. TKIs may have a potential role in the management of EGFR WT patients who are not candidates for chemotherapy. There is a lack of studies on TKIs in EGFR WT patients, and more data with new generation TKIs are needed in this population.