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Anifat Elegbede



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    FP02 - Health Services Research/Health Economics (ID 120)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Health Services Research/Health Economics
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP02.03 - Changing Survival and Treatment Patterns in Patients Aged 80 or Older with Stage IV Non-Small Cell Lung Cancer (NSCLC) (ID 3739)

      00:00 - 00:00  |  Author(s): Anifat Elegbede

      • Abstract
      • Slides

      Introduction

      NSCLC is a disease of the elderly, with a median age at diagnosis of 70 years old. Yet elderly patients with NSCLC are under-represented in clinical trials, and studies of real-world treatment patterns have consistently identified lower rates of systemic therapy administration in this patient population. However there are clinical trial data to suggest that even the very elderly (age 80+) with advanced NSCLC can benefit from system therapy. We therefore looked at real-world patterns of treatment and survival in a cohort of patients aged 80 or older with metastatic NSCLC.

      Methods

      We performed a retrospective analysis of a cohort of 721 patients aged 80 or older diagnosed with de novo stage IV NSCLC in Alberta, Canada between 2011-2016 using the Glans-Look database. Data was derived from the provincial cancer registry and supplemented with additional chart review for a subset of cases. Univariate survival analysis used the Log-Rank method, and multivariate analysis Cox Regression. All other tests were Chi-Squared. Median overall survival (OS) in months is shown with 95% confidence intervals. The number of patients included for specific tests is indicated where the full cohort population is not included.

      Results

      Over the study period, an increasing proportion of patients were treated with systemic therapy (9.5% in 2011-2012, 21.6% in 2015-2016; P < 0.001), and the proportion of patients treated with 1st line targeted therapy also increased (N = 54; 43.8% in 2011-2012, 79.2% in 2015-2016; P < 0.029). Receiving systemic therapy was associated with improved OS (17.53 (14.01 – 21.06) vs 3.67 (3.30 – 4.04) months; P < 0.001). While there was a trend towards improved OS for the entire population over time (median 3.63 (2.99 – 4.27) months in 2011-2012 vs 5.33 (4.36 – 6.30) months in 2015-216; P = 0.19), survival improved significantly for those who received systemic therapy over the study period (median 7.10 (5.087 – 9.11) months in 2011-2012 vs 20.80 (17.09 – 24.51) months in 2015-2016; P = 0.02). There was no significant difference in OS for those who received chemotherapy vs targeted therapy (N=54; 15.97 (7.84 – 24.09) months vs 18.50 (13.05 – 23.95) months; P = 0.74), suggesting that improved access to systemic therapy rather than the intrinsic nature of the therapies themselves underlie improving survival amongst treated patients.

      Conclusion

      We identified increasing rates of systemic therapy use in patients aged 80 or older with de novo metastatic NSCLC, and improving OS amongst treated patients over the study period. While we cannot account for all potentially relevant changes to the management of NSCLC over that time, the improvement in increasing rates of systemic therapy use and survival in treated patients are potentially driven by availability and increasing use of targeted therapies. This suggests that elderly patients with NSCLC have benefited significantly from the use of these medications.

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    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
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      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): Anifat Elegbede

      • Abstract
      • Slides

      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.

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    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
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      P09.04 - Changing Survival and Treatment Patterns in Patients with Stage IV Non-Small Cell Lung Cancer (NSCLC) in Alberta, Canada (ID 3737)

      00:00 - 00:00  |  Author(s): Anifat Elegbede

      • Abstract
      • Slides

      Introduction

      We have previously reported that rapid physical decline and poor performance status means that only a minority of patient with metastatic NSCLC receive systemic treatment. Over the last decade, treatment advances in the form of maintenance chemotherapy, targeted therapies and immunotherapy for advanced disease have shown benefit in randomized phase III trials and been adopted as standard of care. Nevertheless, there are conflicting reports of trends in overall survival. We therefore looked at real-world patterns of treatment and survival in a cohort of patients with metastatic NSCLC.

      Methods

      We performed a retrospective analysis of a cohort of 4400 patients diagnosed with de novo stage IV NSCLC in Alberta, Canada between 2011-2016 using the Glans-Look database. Data was derived from the provincial cancer registry and supplemented with additional chart review for a subset of cases. Univariate survival analysis used the Log-Rank method, and multivariate analysis Cox Regression. All other tests were Chi-Squared. Median survival in months is shown with 95% confidence intervals. The number of patients included for specific tests is indicated in cases where there was missing data.

      Results

      There was a trend towards improving overall survival over the study period (4.67 (4.24 – 5.10) months in 2011, and 5.90 (5.22 – 6.58) months in 2016; univariate P = 0.092). We observed an increasing proportion of patients with no smoking history (N = 1257; 11.2% in 2011 vs 31.6% in 2016; P < 0.001), an increasing proportion of patients receiving systemic therapy (29.1% in 2011 vs 38.0% in 2016; P < 0.001), and an increasing proportion of patients treated with systemic therapy that received 1st line targeted therapy (N = 541; 20.3% in 2011 vs 39.1% in 2016; P < 0.001). These factors were also associated with improved overall survival in univariate analysis: never smoker vs ever smoker (N = 541; 17.47 (14.61 – 20.33) months vs 6.33 (5.47 – 7.19) months; P < 0.001); receipt of systemic therapy (12.00 (11.30 – 12.70) months vs 3.10 (2.94 – 3.26) months; P < 0.001) targeted therapy vs chemotherapy (N = 541 ; 19.30 (16.06 – 22.54) months vs 15.98 (14.37 – 17.56) months; P = 0.015). Younger age at diagnosis, female gender, receiving systemic therapy, and use of 1st line targeted therapy vs chemotherapy were all significantly associated with improved survival in multivariate models (smoking status excluded from analysis due to number of cases with missing data).

      Conclusion

      We observed a trend towards improving survival from 2011 to 2016 in patient with stage IV NSCLC in Alberta, Canada. While we cannot account for all potentially relevant changes to the management of NSCLC over that time, we observed increasing rates of systemic therapy administration and use of 1st line targeted therapy, which may be in part responsible for improving survival.

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    P36 - Pathology - Prognosis (ID 106)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P36.05 - Metastatic NSCLC Outcomes With Guideline-Recommended Treatment By KRAS Subtype (ID 3104)

      00:00 - 00:00  |  Presenting Author(s): Anifat Elegbede

      • Abstract
      • Slides

      Introduction

      The impact of specific KRAS mutation on treatment outcomes remain unclear. We compared the association between systemic anti-cancer treatment (SACT) outcomes and specific KRAS mutations [G12C versus non-G12C mutants] in metastatic non-squamous NSCLC patients (mNSCLC).

      Methods

      Patients’ data were retrieved from the institutional Glans-Look Lung Cancer Research database. mNSCLC (AJCC TNM 8th edition Stage IV) treated with guideline-recommended first-line SACT (1L) in Southern Alberta, Canada during 2018-2020 periods were included while excluding those with concurrent multiple malignancies. Outcomes including overall response rate (ORR, RECIST v1.1), adverse events (CTCAE criteria v5), progression-free and overall survival were compared using descriptive (Fisher’s Exact test), Kaplan-Meier survival (Log-Rank) and multivariate (Cox Proportional Hazard) statistics. A priori statistical significance was p < 0.05. Analyses were performed using SPSS statistical software (version 25).

      Results

      A total of 86 KRAS mutant mNSCLC were identified with a preponderance of G12C variant (45%) and women (63%). The non-G12C includes 36% G12V, 15% G12A, 13% G12D, 13% Q61H & 23% others. The median age was 67 years, ECOG performance of 0-1 in 52%, ≥2 in 28% and unknown in 20%. 95% were adenocarcinoma and 55% PD-L1 high (>50%). 1L were 51% pembrolizumab, 30% platinum-based chemotherapy and 17% pembrolizumab/chemotherapy. About 70% already discontinued 1L. 2L rate was 23%, immune therapy was the most common (55%).

      KRAS mutant G12C versus non-G12C differ by gender with more female only in G12C (p=0.02) and ECOG status at presentation with less ECOG 0-1 in G12C (p<0.01). Pembrolizumab was the commonest 1L regimen in both subtypes.

      Outcomes by SACT are summarized in Table 1. There were similar 1L treatment outcomes in G12C vs. non-G12C: ORR (21 vs. 30%, p=0.37), disease progression rate (67 vs 68%, p>0.05), grade ≥3 adverse event (8 vs. 9%, p=0.42) or immune-related events (18 vs 19%, p>0.05), median progression-free (5 vs. 6 months, p=0.9) and overall survival (15 months vs not yet reached, p=0.6). 31% of G12C received 2L versus 17% in non-G12C.

      Only pembrolizumab relative to chemotherapy receipt was significantly associated with better PFS [HR (chemotherapy)=2.34 (95 CI: 1.04-5.29)] and OS [HR (chemotherapy)=3.25 (1.17-9.0)] in multivariate analyses.

      G12C vs. non-G12C mutant KRAS NSCLC

      Pembrolizumab

      (n= 44)

      Chemotherapy

      (n=26)

      Chemo/pembro

      (n=16)

      Uptake rate, %

      56 vs. 47

      28 vs. 32

      15 vs. 21

      DCR (PR & stable), %

      59 vs. 55

      55 vs. 53

      83 vs. 60

      PR-partial response, %

      (n)

      23 vs. 36

      (5 vs 8)

      0 vs. 20

      (0 vs 3)

      50 vs. 30

      (3 vs. 3)

      Stable disease, %

      (n)

      36 vs 18

      (8 vs 4)

      55 vs 33

      (6 vs 5)

      33 vs 30

      (2 vs 3)

      PFS, median, mo

      15 vs. 19

      6 vs. 7

      10 vs. 8

      PFS, HR for non-G12C (95% CI)

      0.97 (0.48-2.00)

      PFS, HR for Platin doublet

      (Pembro as reference)

      2.48 (1.10-5.60)**

      PFS, HR for Platin/pembro

      (Pembro as reference)

      1.52 (0.41-5.67)

      OS, median, mo

      18 vs. NR

      6 vs. 7

      Both= NR

      OS, HR for non-G12C (95% CI)

      0.51 (0.22-1.17)

      OS, HR for Platin doublet

      (Pembro as reference)

      3.25 (1.17-9.0)**

      OS, HR for Platin/pembro

      (Pembro as reference)

      1.39 (0.31-6.33)

      Table 1: Comparison of guideline-recommended treatment outcomes between G12C and non-G12C mutant KRAS metastatic non-squamous NSCLC

      ** denotes statistical significance

      CI= confidence interval, DCR= disease control rate, HR= hazard ratio, OS= overall survival, PFS= progression-free survival, mo. = month

      67 Conclusion

      There was no significant difference in response or survival outcomes with 1L in specific mutant KRAS variants (G12C versus non-G12C). 2L receipt in ~1/3rd of G12C mutant patients suggest there may be greater appetite for further treatment of progressive disease should more tolerable treatment becomes available.

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    P50 - Small Cell Lung Cancer/NET - Real World Outcomes (ID 232)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 3
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P50.01 - A Year Experience With Atezolizumab Plus Chemotherapy For Small Cell Lung Cancer In Alberta, Canada (ID 1945)

      00:00 - 00:00  |  Presenting Author(s): Anifat Elegbede

      • Abstract
      • Slides

      Introduction

      The authors assessed the real-world effectiveness of newly approved regimen, atezolizumab plus carboplatin-etoposide (Atezo-CaE) for extensive stage (ES) small cell lung cancer (SCLC) in Alberta, Canada. Atezo-CaE is yet to be provincially funded for ES treatment but can be accessed through special access programs.

      Methods

      Included in this study were confirmed ES patients treated with first-line Atezo-CaE at the tertiary and community cancer care centres in Alberta, Canada post FDA/ Health Canada approval (2019) up to the data cut-off date (September 1, 2020). Demographic and clinical data were extracted from the institutional Glans-Look Research Database. Any with active multiple malignancies and/or prior curative-intent treatment were excluded. Outcomes including overall response rate (ORR, RECIST v1.1), adverse events (CTCAE criteria v5), progression-free and overall survival were estimated using descriptive and Kaplan-Meier survival (Log-Rank) statistics. A priori statistical significance was p < 0.05. Analyses were performed using SPSS statistical software (version 25).

      Results

      There were 34 patients seen at the community care centres (18%) or academic tertiary institutions (82%). 53% were male, 24% had ECOG performance status ≥2 and the median age was 65 years. The median number of days from diagnosis to Atezo-CaE receipt was 40 (range: 14-128) days. 21% had no maintenance atezolizumab. In addition, 65% had radiotherapy treatment.

      21% were still having ongoing atezolizumab treatment. The median duration of atezolizumab was 4.2 (range: 0.1-13.5) months. ORR was 62% with a median of 84 (range: 47-210) days time to best response. 18% have an ongoing response to atezolizumab.

      Disease progression was the commonest reason for 1L discontinuation while also accounting for the 2nd most common reason for no maintenance atezolizumab only after adverse events. Overall, progressive disease rate was 76%. The median duration of response was 98 (range: 35-635) days. 24% continued atezolizumab for ≥ 1 month past disease progression. 2L rate was 26%.

      The median progression-free and overall survival for all patients were 6 (95% CI: 4-8) and 11 (95% CI: 9-11) months while in those who received maintenance atezolizumab were 8 (p=0.01) and 13 (p<0.01) months respectively.

      Conclusion

      Within a year of Atezo-CaE treatment for ES, there was 18% ongoing response to Atezo-CaE. The ORR (62 vs 60%), median treatment duration (4.2 vs 4.7 months) and overall survival outcomes (12.7 vs 12.3 months) appeared consistent in real-world versus clinical trial patients1. Future study to identify factors predicting Atezo-CaE treatment response and survival outcomes in SCLC is very much needed.

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      P50.02 - Survival Outcome Comparison in Metastatic Small Cell Lung Cancer (SCLC) at Diagnosis Versus at Relapse (ID 1946)

      00:00 - 00:00  |  Presenting Author(s): Anifat Elegbede

      • Abstract
      • Slides

      Introduction

      We have previously reported increased survival in relapsed compared to de novo metastatic non-SCLC (NSCLC) patients. This study compared outcomes between real-world SCLC patients with extra-pulmonary metastasis at diagnosis (de novo) and at relapse in Alberta, Canada.

      Methods

      Included in this study were 2010-2016 SCLC diagnoses with extra-pulmonary metastasis de novo or at relapse either extensive disease/TNM stage IV and have had palliative chemotherapy or limited disease/TNM stage I-III and have had curative intent chemo-radiation. Data were retrieved from the Glans-Look database excluding patients with non-guideline-recommended treatment or those untreated at diagnosis. The main outcome was post-metastatic survival i.e. the time in months from metastatic disease diagnosis date to death/last contact.

      Comparison between relapsed and de novo groups was performed using Fisher’s Exact (point estimates), Log-Rank tests (Kaplan-Meier survival estimates) and Cox proportional hazard model (survival outcome predictors). Analyses were performed using SPSS statistical software (version 25) with a priori statistical significance at p<0.05.

      Results

      215 patients were identified; 54% were female, and the median age at metastasis was 67 years. 1, 12 and 87% were stage I-II, III and IV respectively.

      78% were de novo and 9% relapsed extensive stage (ES), while 13% were relapsed limited stage (LS) patients with extra-pulmonary metastases. Rates of multi-sites [p<0.01] and site-specific metastases including adrenal [p=0.02), bone [p=0.13] and liver [p=0.01] were higher in de novo than the relapsed group, except for brain metastasis which was more in the latter group (relapsed LS and ES), p= 0.25.

      Relapsed patients experienced 6 months survival compared to 8 months in de novo group [p=0.02]. This survival benefit persisted when stratified by presence [p=0.16] or absence of brain metastasis [p=0.02]. Between-stage comparison showed no significant difference in relapsed LS versus de novo ES [OS= 8 vs. 9 mo, p=0.22]. Only female sex [HR for male vs. female= 1.38, p=0.04] and chemotherapy for metastasis [HR= 0.21, p<0.01] correlated with favorable survival in multivariate analyses. 41% of relapsed LS had palliative chemotherapy at metastasis.

      In contrast, within-stage comparison revealed better survival for de novo than relapsed ES [9 vs 5 mo., p=0.02], and after adjustment for potential confounders e.g. age, ECOG status, metastatic burden, radiotherapy receipt (RT) [HR for relapsed ES= 2.84, p= 0.03]. Paradoxically, presence of brain metastasis correlated with favorable survival for ES patients [HR= 0.64, p=0.01]. Of note, relapsed ES tends to have more ≥65 year population [80 vs 58%, p=0.18] and higher RT [95 vs 69%, p<0.01], relative to de novo ES. 25% of relapsed ES received chemotherapy for metastatic disease.

      Conclusion

      While we found a significant post-metastatic survival benefit in de novo versus relapsed ES, we observed no significant difference between de novo ES and relapsed LS. This underscores the importance of taking caution when providing prognostic estimates with relapsed versus de novo metastatic disease for SCLC and NSCLC patients.

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      P50.10 - Intravenous (IV) versus IV/oral route of etoposide administration: impact on real-world SCLC survival outcomes (ID 1944)

      00:00 - 00:00  |  Presenting Author(s): Anifat Elegbede

      • Abstract
      • Slides

      Introduction

      Platinum-etoposide doublet (PE) is the recommended first-line (1L) chemotherapy for small cell lung cancer (SCLC). Evidence shows that oncology patients prefer oral treatment to IV. This study compared outcomes between 1L intravenous (IV), and IV followed by oral (IV/oral) route of etoposide administration in real-world SCLC patients in Alberta, Canada.

      Methods

      SCLC patients who were diagnosed between 2010 and 2016 and completed 1L etoposide at an academic tertiary cancer centre, (Tom Baker Cancer Centre) were included. Data were retrieved from the Glans-Look database excluding those with mixed histology. Outcomes explored included, a] overall survival, (OS), the time in months from diagnosis date to death/last contact, b] tumor objective response rate (ORR), the complete and partial responses as defined by the RECIST v1.1 criteria, using diagnostic imaging reports within 4-8 weeks post 1L or as reported in oncologist progress notes, and c] 1L-related toxicity rate, derived from progress notes, graded using the CTCAE criteria (version 5). Also measured was the progression free survival (PFS): time difference in months from diagnosis date to first progression post 1L or death, whichever occurs first.

      Comparison between IV/oral and IV groups was performed using Fisher’s Exact (point estimates), Log-Rank tests (Kaplan-Meier survival estimates) and Cox proportional hazard model (survival outcome predictors). A priori statistical significance was p < 0.05. Analyses were performed using SPSS statistical software (version 25).

      Results

      There were 222 patients, 1L was mostly PE [93%] employing etoposide in combination with cisplatin [61%] or carboplatin [32%]. 168 [76%] were IV/oral group. Median age was 66 years, 132 [60%] female, and 138 [62%] had extensive stage SCLC (ES). Performance status (ECOG) was 0-2 in 112 (51%), ≥3 in 9 (4%) and unknown in 101 (46%) patients. IV and IV/oral patients have similar characteristics, but compared to IV/oral, the IV group had less limited stage disease (LS), [p=0.28].

      100 patients experienced grade 3 or 4 toxicities, mainly neutropenia [83%]. The rates were similar for IV/oral versus IV group, p= 0.36. Stratified by stage however, toxicity from IV was greater in LS than ES patients [60 vs 39%]. Overall, ORR for IV/oral versus IV group was 71% vs 66%, [p=0.85]. Within stage, ORR was 79 vs. 89% in LS [p< 0.01] and 58 vs 71% in ES [p=0.23], IV/oral relative to IV group.

      There was no statistically significant difference in PFS or OS with IV/oral relative to IV groups [PFS: 14 vs 12 months for LS; both 6 months for ES; OS: 32 vs 25 mo. for LS; 12 vs 14 mo. for ES]. Predictors of favorable survival include presence of grade 3 or 4 toxicity in LS [HR= 0.45, p=0.03] and second-line chemotherapy receipt in ES [HR= 0.46, p<0.01].

      Conclusion

      Consistent with previous reports, we found high oral treatment rate in real-world SCLC patients and no statistically significant differences in SCLC survival outcomes comparing IV/oral versus IV group. Future studies may explore why severe chemotherapy-related toxicity (grade 3 or 4) in LS patients predicts favorable survival.

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    P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P76.17 - Prognostic Role of the Systemic Immune-Inflammatory Index (SII) in Driver-Mutation Positive NSCLC: Real-World EGFR-Mutant Disease (ID 1186)

      00:00 - 00:00  |  Author(s): Anifat Elegbede

      • Abstract
      • Slides

      Introduction

      The role of the tumour microenvironment is recognized as playing a significant role in cancer progression and patient survival. Prognostic indices derived from peripheral blood components are employed as an indicator of tumour microenvironment, and have shown prognostic utility in a number of solid tumors. Within non-small cell lung cancer (NSCLC), haematologically derived prognostic indices have shown an association with outcome in advanced disease treated with immune checkpoint inhibitors and in early-stage resected tumors, but few studies have sought to evaluate the predictive ability of prognostic markers in advanced NSCLC on targeted therapy, aside from a recognized association between elevated lactose dehydrogenase (LDH) and poor prognosis in this population. In response, we aimed to evaluate the potential of an innovative and inexpensive marker, the systemic immune-inflammatory index (SII), as a prognostic tool in metastatic EGFR-mutant NSCLC receiving first-line tyrosine kinase inhibitor therapy (EGFR-TKI) in the real-world setting.

      Methods

      Alberta patients with a diagnosis of de novo metastatic EGFR-mutant NSCLC and receiving frontline EGFR-TKI between 2010 and 2018 were identified, and their demographic, clinical, treatment and outcome data were extracted from the institutional Glans-Look Lung Cancer Database. SII was calculated as pre-treatment (≤ 30 days prior to EGFR-TKI initiation) platelet count multiplied by neutrophil count, divided by lymphocyte count. Receiver operator characteristic (ROC) curves were constructed to identify optimal cut-off points for SII, and patients were stratified by this factor. Univariate analysis was performed to assess differences between high and low SII groups, and Kaplan-Meier survival analysis employing the log-rank test was conducted to estimate overall survival (OS) and progression-free survival (PFS).

      Results

      220 patients were identified. Median age was 65.6 years, 59% never-smokers, 64% female, 85% Exon 19 or 21 mutation. 75% were treated with gefitinib, 25% afatinib in the first-line setting.

      An optimal cut-off value for SII of 1200 was identified using ROC and applied; 55% of patients had ‘high’ SII. Compared to patients with low-SII, patients with high-SII had significantly shorter PFS (15.6 vs 10.8 months, p < 0.001) and OS (30.4 vs 20.1 months, p < 0.001).

      Low-SII and high-SII patients were clinicopathologically similar, apart from an association between high-SII and elevated lactate dehydrogenase (LDH).

      LDH was elevated, according to laboratory derived cut-off values (> 235 U/L), in 56% of patients; we combined LDH value with SII to create a risk factor count, identifying the number of elevated markers (LDH and SII) present (none, one or two). Patients were then stratified according to number of risk factors, and OS and PFS investigated: 26% of patients had no elevated markers, 37% one elevated marker, 37% two elevated markers, with median PFS of 15.7, 13.9, 9.5 months, respectively (p< 0.001), and median OS of 32.8, 26.3, and 17.6 months, respectively (p<0.001).

      Conclusion

      This study demonstrates that elevated SII is a strong prognostic indicator, associated with shortened PFS and reduced OS in metastatic EGFR-mutant NSCLC on first-line EGFR-TKI. Enumerating the presence of elevated SII and LDH can create a simple and cost-effective indicator of outcome within this real-world population.

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    P89 - Targeted Therapy - Clinically Focused - Translational (ID 266)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P89.12 - Real World Outcomes in EGFR-Mutant Relapsed and De Novo Stage IV Non-Small Cell Lung Cancer (NSCLC) (ID 1184)

      00:00 - 00:00  |  Author(s): Anifat Elegbede

      • Abstract
      • Slides

      Introduction

      Differences in post-metastatic disease survival has been previously established in NLCLC, whereby patients with ‘de novo’ disease (metastases at diagnosis) show significantly poorer prognosis than ‘relapsed’ patients (initial early stage disease with subsequent development of metastatic disease after curative-intent therapy). We used a real-world population to investigate if this phenomenon also exists within biomarker positive EGFR-mutant patients.

      Methods

      Alberta NSCLC patients with an EGFR mutation detected 2010-2017 were identified, and classified as either ‘relapsed’ or ‘de novo’. Demographic, clinical, treatment and outcome data were extracted from the institutional Glans-Look Lung Cancer Database. Univariate methods were used to assess differences in clinicopathological features and median overall survival (mOS), the interval from diagnosis to death, and median post-metastatic disease survival (mPMDS), the interval from the date of metastatic disease discovery to death.

      Results

      324 patients with metastatic disease were identified. 85% de novo metastatic disease, 65% female, 60% < 70 years at treatment initiation for metastatic disease, 54% never smokers, 94% with a single EGFR mutation. 93% received tyrosine-kinase inhibitor therapy, 15% of which received subsequent osimeritinib therapy for T790M resistance acquisition.

      De novo and relapsed patients did not differ significantly in terms of demographic or clinicopathological factors.

      83% were deceased at the time of analysis; mOS of the entire cohort was 24.0 months [95% CI: 21 to 26 months] and mPMDS was 23.2 months [95%CI: 18.0 to 24.6 months]. Relapsed patients showed significantly superior survival times, both in terms of mOS [56 months vs. 21 months, log rank p<0.001] as well as mPMDS [30.1 vs. 21.6 months, log rank p < 0.001].

      Conclusion

      Among EGFR-mutant NSCLC patients, relapsed patients demonstrate a distinct survival advantage, while appearing clinically indistinguishable from de novo patients. This information reinforces the importance of considering the timing of onset of metastatic disease as a clinically useful variable when determining prognosis, and suggests consideration of this factor an important potential addition to clinical trial design.

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