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Dae Ho Lee



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    EP1.01 - Advanced NSCLC (ID 150)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.01-03 - Real World Outcome of Crizotinib for Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer Patients (Now Available) (ID 141)

      08:00 - 18:00  |  Author(s): Dae Ho Lee

      • Abstract
      • Slides

      Background

      Crizotinib has shown its superiority in clinical trials compared to conventional chemotherapy in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patient, but its use and outcomes in real-world settings are yet to be investigated. This study aimed to assess treatment patterns and outcomes of crizotinib therapy in ALK-positive NSCLC patients, as well as to seek factors associated with progression-free survival and overall survival of ALK-positive NSCLC patients.

      Method

      A retrospective medical record review of 176 patients who are diagnosed as metastatic or recurred NSCLC from January 1st, 2006 to June 30th, 2018 and treated with crizotinib was performed. Descriptive analyses were conducted to assess treatment patterns and objective response rate (ORR). Survival analysis to estimate progression-free survival (PFS) and overall survival (OS) was performed. Comparison of the treatment outcomes by the setting of crizotinib initiation was done. Cox regression analysis was used to find predictive factors associated with PFS and OS from initiation of crizotinib.

      Result

      Median age was 55.7 (ranged 20 to 84) years and 85 patients (48.3%) were male. Seventy-two (40.9%) patients died at the time of analysis. Seventy-eight patients initiated crizotinib as first-line therapy. Overall response rate was 54.5% (50.0% for first-line recipients, 58.2% for second-/later-line). Median (95% CI) PFS from crizotinib initiation and OS from first dose of chemotherapeutic agent were 14.3 (11.6-17.0) and 41.7 (25.4-58.1) months, respectively. No significant difference of ORR, OS, and PFS, according to the setting of crizotinib initiation was observed. Multivariate Cox analysis showed poor performance status (HR 3.472, p-value < 0.001) and number of metastatic organs (≥3, HR 1.648, p-value 0.017) were independently associated to shorter PFS and OS, while history of getting pemetrexed before use of crizotinib (HR 0.638, p-value 0.039) was independently related to longer OS.

      All patients

      Setting of Crizotinib Initiation

      (n = 176)

      First-Line

      (n = 78)

      Second- or Later-Line

      (n = 98)

      P value

      Progression-free survival

      0.699

      Mean (SE)

      25.0 (3.1)

      28.0 (6.4)

      16.6 (1.5)

      Median (95% CI)

      14.3 (11.6-17.0)

      15.8 (10.0-21.6)

      13.1 (9.1-17.0)

      Q1, Q3

      5, 27

      5, 22

      5, 27

      Overall survival

      0.137

      Mean (SE)

      54.1 (4.2)

      40.6 (6.1)

      57.8 (4.9)

      Median (95% CI)

      41.7 (25.4-58.1)

      26.3 (14.7-37.9)

      43.9 (25.7-62.1)

      Q1, Q3

      18, 109

      17, 77

      19, 109

      1- and 2-year survival rates

      Percent still alive at 1 year after diagnosis (95% CI)

      87.1 (86.7-87.5)

      85.4 (84.3-86.5)

      88.5 (87.8-89.2)

      0.483

      Percent still alive at 2 years after diagnosis (95% CI)

      65.7 (65.0-66.4)

      55.4 (51.9-58.9)

      69.0 (68.0-70.0)

      0.213

      Conclusion

      Outcomes for crizotinib recipients were in line with previous trials, with PFS and OS appearing more favorable. Poor performance status and number of metastatic organs correlated to worse PFS and OS, while history of previous use of pemetrexed before crizotinib correlated to better OS.

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    P1.14 - Targeted Therapy (ID 182)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.14-53 - Co-Occurring CDKN2A/2B Alteration Is Associated with Poorer Survival in ALK-Positive Lung Cancer (ID 1536)

      09:45 - 18:00  |  Author(s): Dae Ho Lee

      • Abstract

      Background

      Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have shown promising clinical outcomes for ALK-positive (ALK+) lung cancer patients. However, clinical outcomes are varied, distinct mechanisms have been suggested for different ALK fusion variants or co-occurring mutations in response to various TKIs. We analyzed whether variants or co-occurring mutations influence the outcome of AKL TKI treatment in ALK+ non-small-cell lung cancer (NSCLC).

      Method

      Between March 2017 and October 2018, 489 NSCLC tumor specimens were examined with OncoPanel AMC version3 which is a NGS based assay for the detection of single-nucleotide variants, insertions, deletions, copy number alterations and structural variants across 382 genes. 43 patients were identified as having ALK rearrangement. And 37 patients received ALK TKI treatment. Progression free survival (PFS) and overall survival (OS) were analyzed respectively according to ALK variants and other co-occuring mutations.

      Result

      Among 37 patients with ALK+ NSCLC, 32 (86.5%) of patients received crizotinib, and 5 (13.5%) with alectinib as first ALK TKI treatment. The most frequent ALK variant was variant 3a/b in 13 patients (35.1%), followed by variant 1 in 10 patients (27.0%), variant 5 in 4 patients (10.8%), variant 2 in 3 patients (8.1%), and others in 7 patients (18.9%). The similar median PFS was observed in patients ALK variant 3 and non-variant 3 regardless of first ALK TKI treatment strategy (crizotinib, 18.9 vs. 15.2 months, p=0.35; alectinib, both not reached). As a co-occurring mutation, TP53 mutation was detected in 17 (45.9%) patients. And there was no statistical difference in PFS or OS between the wild type and TP53 mutation group [PFS 18.2 vs 15.3 months, p=0.92; OS 62.1 vs 62.2 months, p=0.44]. CDKN2A/2B alteration was the second most common mutation and observed in 9 (24.3%) patients. Median PFS and OS in ALK-CDKN2A/2B co-mutated patients were lower than wild type patients [PFS 15.3 months (95% CI: 8.1-22.5) versus 18.2 months (95% CI: 13.0–23.4), P=0.064, OS 26.7 months (95% CI: 14.2–39.3) versus not reached, P=0.022].

      Conclusion

      In ALK+ NSCLC, having co-occurring CDKN2A/2B alteration was associated with a poorer OS when treated with an anti-ALK agent.