Virtual Library

Start Your Search

Daniel E. Meyers



Author of

  • +

    FP07 - Pathology (ID 109)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
    • +

      FP07.07 - Value of the Lung Immune Prognostic Index (LIPI) As a Prognostic Tool for Real-World Patients Treated for Mutation-Positive Metastatic NSCLC (ID 3683)

      00:00 - 00:00  |  Author(s): Daniel E. Meyers

      • Abstract
      • Presentation

      Introduction

      LIPI is a prognostic index which has demonstrated strong utility in metastatic NSCLC (mNSCLC) patients when treated with immune checkpoint inhibitors (ICIs). Recent pooled analysis using clinical trial data suggests that LIPI scores may also be prognostic of outcome in patients with mNSCLC treated with non-ICI systemic therapies such as tyrosine kinase inhibitors (TKIs) and cytotoxic chemotherapy (CTx).

      Recognizing both the increasing number of patients with mNSCLC who possess mutation-positive tumours and the potential differences between clinical trial and real-world patient populations, we sought to explore the prognostic ability of the LIPI among real-world mutation-positive mNSCLC patients in receipt of palliative-intent systemic therapy.

      Methods

      Alberta patients diagnosed 2015-2019 with mutation-positive (KRAS, ROS1, EGFR or ALK) mNSCLC, in receipt of palliative-intent first-line TKI, CTx or ICI systemic therapy were identified. Demographic, clinical, treatment and outcome data were extracted from the institutional Glans-Look Lung Cancer Database. LIPI scores were calculated using blood component values taken ≤30 days prior to first-line systemic therapy initiation. Kaplan-Meier analysis assessed the impact of LIPI score on progression-free survival (PFS) and overall survival (OS), and Cox Proportional Hazards models were constructed to control for potential confounders and identify factors which had prognostic value.

      Results

      158 patients were identified (Table 1):

      lipi impact_table1.jpg

      Survival analysis revealed that LIPI was not significantly associated with outcome (PFS and OS) in the pooled cohort or by individual mutation, and only showed an association with outcome among the cohort of ICI-treated patients (all PD-L1 > 50%) where a previously established inverse relationship between LIPI score and median PFS/OS has been previously observed. ECOG was revealed to have better association with outcome, whereby ‘good’ ECOG (0 or 1) patients, when compared to ‘poor’ ECOG (2+) experienced significantly longer PFS (19.2 vs. 11.4 months p<0.001) and OS (34.4 vs. 12.1 months, p<0.001) in the pooled cohort, with this similar pattern observed within the ALK, EGFR and KRAS mutant populations.

      A Cox proportional hazards model, constructed for the pooled cohort and controlling for known confounders (age, sex, treatment, smoking history and mutation type) revealed that poor ECOG is prognostic of reduced PFS (HR: 3.6, p<0.001) and OS (HR: 3.6, p<0.001), while never-smoking history (HR: 0.26, p<0.001) and female sex (HR: 0.5, p=0.03) were prognostic of increased OS.

      Conclusion

      Among real-world mutation-positive mNSCLC, ECOG serves as a better prognosticator of outcome than LIPI score. The utility of LIPI in this population remains limited to those treated with ICI therapy.

      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.

  • +

    P09 - Health Services Research/Health Economics - Real World Outcomes (ID 121)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Health Services Research/Health Economics
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
    • +

      P09.08 - Age-Related Outcomes of First-Line Pembrolizumab in a Real-World Non-Small-Cell Lung Cancer (NSCLC) Cohort (ID 3451)

      00:00 - 00:00  |  Author(s): Daniel E. Meyers

      • Abstract
      • Slides

      Introduction

      On the basis of the KEYNOTE-024 trial, pembrolizumab became standard of care in Canada for patients with PD-L1 positive (≥50%) NSCLC. However, robust real-world data assessing outcomes in this treatment setting, especially amongst patients of different age groups, are lacking. The primary objective of this study was to examine age-related outcomes in a real-world cohort of NSCLC patients treated with pembrolizumab.

      Methods

      Patients who initiated first-line, single-agent pembrolizumab for treatment of PD-L1-positive (≥50%) NSCLC in Alberta, Canada from 3/1/2017 to 12/30/2019 were included. Data cutoff date was 05/01/2020. Patient demographics and clinical outcomes were collected retrospectively. The primary outcome was median overall survival (mOS) among age-stratified groups. Secondary outcomes were median time-to-treatment failure (mTTF) and objective response rate (ORR). Kaplan-Meier survival curves were used to determine survival outcomes, and compared with the log-rank test. A Cox-proportional hazard model was constructed with relevant clinical characteristics to assess their impact on survival.

      Results

      Of the 327 patients included in the analysis, 31% (n=101) were <65 years old, 45% (n=147) were between 65-74 years old and 24% (n=79) were ≥75 years old. mOS (95% CI) was 12.3 mo (8.3-17.5) for the entire cohort. Stratified by age, mOS between the groups were not significantly different (15.4 mo [6.0-23.8], 9.3 mo [6.8-16.5], and 14.4 mo [8.2-23.2] for the <65, 65-74, and ≥75 age groups, respectively; p=0.81). In addition, neither the mTTF nor ORR differed between age groups (p=0.59 and p=0.86, respectively). All three groups had similar 90-day mortality rates after treatment initiation; 29.7%, 23.8%, and 17.7% (p=0.18) and similar survival at 12 months (39.6%, 32.7%, and 31.6%, p=0.43).

      In a multivariate model accounting for sex, age, tumor histology, baseline autoimmune disease, presence of brain metastases, and Eastern Cooperative Oncology Group Performance Status (ECOG-PS), only ECOG-PS ≥ 2 was an independent prognosticator of poor survival (HR 2.9; 95% CI 2.1-4.0, P < 0.0001).

      Table 1. Clinical outcomes as stratified by age

      <65 Cohort (n=101)

      65-74 Cohort (n=147)

      75 Cohort (n=79)

      p-value

      mOS (95% CI)

      15.4 (6.0-23.8)

      9.3 (6.8-16.5)

      14.4 (8.2-23.2)

      0.81a

      mTTF (95% CI)

      4.5 (2.1-5.5)

      3.7 (2.8-4.9)

      5.6 (2.8-7.7)

      0.59a
      %ORR^ 29.6% 32.5% 33.9% 0.86b
      % alive at 90 d 70.3% 76.2% 82.3% 0.18b
      % alive at 12 mo 39.6% 32.7% 31.6% 0.43b

      ^Calculated from evaluable responses. alog-rank test. bchi-squared test.

      Conclusion

      There were no significant differences in mOS, mTTF, or ORR between the age-stratified treatment groups in our sample. Notably, we observed a ~25% mortality rate within the first 90-days of treatment initiation, and a mOS of only 12.3 mo. ECOG-PS ≥ 2 was the only significant prognosticator of poor OS. Although we conclude that age alone should not be a contraindication to treatment with first-line pembrolizumab in PD-L1-positive NSCLC, survival outcomes are modest compared to the KEYNOTE-024 trial, with poor ECOG-PS being the strongest negative prognostic factor.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    P16 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) - Novel Immunotherapeutics (Translational) (ID 155)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
    • Presentations: 2
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
    • +

      P16.02 - Impact of Number and Location of Metastatic Sites on Survival in Stage IV ICI-Treated NSCLC (ID 1180)

      00:00 - 00:00  |  Author(s): Daniel E. Meyers

      • Abstract
      • Slides

      Introduction

      Use and efficacy of immune checkpoint inhibitors (ICI) in heterogeneous real-world populations remains an area of interest; in response, we investigated the impact of number of involved organs and location of metastatic disease (NM; LM) on the post ICI-initiation survival (ICI-OS) and progression-free survival (PFS) of real-world NSCLC patients undergoing ICI therapy.

      Methods

      Demographic, clinical, treatment and outcome data for Stage IV NSCLC patients treated with nivolumab or pembrolizumab ICIs between 2015-2018 was extracted from the institutional Glans-Look Lung Cancer Database. Univariate and multivariate analyses were performed to explore the impact of NM and LM on outcome.

      Results

      302 NSCLC patients receiving ICI were evaluated. Median age at ICI treatment onset was 67.2 years, 51% male, 89% ever-smokers, 47% PDL-1 expression > 1%, 81% prior systemic therapy, 65% ECOG < 2, and 47% possessed 1 NM. Top LM, with or without other LM, was intrathoracic (59%), brain (40%), and ‘other’ (24%). Intrathoracic metastases were less commonly associated with other sites; bone was more frequently associated with liver metastases (p<0.001), as was adrenal with brain metastases (p<0.001). For the entire cohort, ICI-OS and PFS were 7.1 and 2.5 months, respectively.

      Survival analysis revealed increasing NM was associated with significantly decreased ICI-OS (p<0.001) and PFS (p=0.001), but in multivariate analysis, controlling for confounders, only NM > 2 was prognostic of poorer ICI-OS (HR: 1.6 95% CI: 1.2-2.1, p=0.002).

      Investigation of LM revealed ICI-OS was best in those with adrenal metastases, worst in those with liver metastases (8.6 vs. 4.6 months, p=0.04), as was PFS (2.1 vs. 1.6 months, non-significant, p=0.12). Multivariate analysis, controlling for confounders, identified liver metastases associated with reduced ICI-OS (HR: 1.5, 95% CI: 1.04-2.4, p=0.03) and bone metastasis was associated with shorter PFS interval [HR: 1.5, 95% CI: 1.03-2.0, p=0.03).

      Conclusion

      Our results demonstrate that liver and bone metastases signal poorer prognosis and shorter PFS, respectively, in ICI treated patients. However, a simple count of NM is a strong prognostic tool, where increasing number of metastatic sites at ICI initiation shows a strong and inverse relationship with the survival after the start of ICI therapy.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

    • +

      P16.03 - Early Mortality Associated Factors With Immune Checkpoint Inhibition in Real-World Canadian NSCLC Patients (ID 1183)

      00:00 - 00:00  |  Author(s): Daniel E. Meyers

      • Abstract
      • Slides

      Introduction

      Immune checkpoint inhibitors (ICI) have been demonstrated to improve survival in metastatic non-small cell lung cancer (mNSCLC); however, within randomized controlled trials the phenomena of early crossover of Kaplan-Meier survival curves favouring the control group suggests a subpopulation of NSCLC patients at risk for early mortality (EM), even among these carefully selected patients. Given the increased heterogeneity and often poorer functional status of real-world patients, we sought to explore the frequency of, and factors associated with, EM for unselected real-world patients receiving ICI.

      Methods

      Clinical, treatment and outcome data for mNSCLC patients, in receipt of ICI between 2015 and 2018, were extracted from the institutional Glans-Look Lung Cancer Database. EM was defined as death from any cause within 60 days of ICI initiation. Univariate analysis was performed to compare EM/non-EM cohorts, and significant factors included in multivariate analysis.

      Results

      A total of 339 patients with mNSCLC receiving ICI were evaluated. 58% received nivolumab and 42% pembrolizumab, primarily in the 2L+ setting (79%), with a median post-ICI initiation survival (mICI-OS) of 8.6 months.

      15% experienced EM. Compared to the non-EM cohort, the EM cohort had reduced mICI-OS (30 days vs. 11.1 months), and were more likely to have abnormal baseline lab values, age < 70 years at ICI treatment start and ECOG > 1, but were less likely to report an adverse event. 71% of the EM cohort had progressive disease (PD) documented before death, at a median 29 days after ICI-initiation, compared to 3.8 months for non-EM; 29% of the EM cohort died before response to treatment could be quantified. Binomial logistic regression identified a neutrophil-lymphocyte ratio ≥ 5 [odds ratio (OR): 3.5; 95% CI 1.2 – 9.8; p=0.02], Albumin < 33g/L [OR: 3.1; 95% CI 1.3 – 7.3, p=0.01], and lactate dehydrogenase > 234U/L [OR: 3.8; 95% CI 1.5 – 9.4; p=0.004] as significant predictors of EM.

      Conclusion

      Early development of PD was common among patients with EM, who differed clinically from non-EM patients. Abnormal baseline laboratory values significantly predicted EM, but neither age nor ECOG were independent predictors of early mortality when controlling for confounders. This suggests careful consideration of baseline laboratory metrics for patients eligible to receive ICI therapy is required to identify those with low likelihood of benefit.

      Only Active 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 or select "Add to Cart" and proceed to checkout.