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Adrian Box



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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): Adrian Box

      • 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.

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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  |  Author(s): Adrian Box

      • 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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