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Sang-we Kim



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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): Sang-we Kim

      • 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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    MA09 - EGFR & MET (ID 128)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
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      MA09.09 - Long-Term Outcomes to Tepotinib Plus Gefitinib in Patients with <i>EGFR</i>-Mutant NSCLC and MET Dysregulation: 18‑Month Follow-Up (Now Available) (ID 1783)

      15:15 - 16:45  |  Author(s): Sang-we Kim

      • Abstract
      • Presentation
      • Slides

      Background

      In EGFR-mutant NSCLC, MET amplification may cause resistance to EGFR tyrosine kinase inhibitors (TKIs). In a Phase Ib/II study in EGFR TKI-resistant patients with EGFR-mutant MET+ NSCLC, progression-free survival (PFS) and objective response rate (ORR) after ≥6 months of follow-up were improved with tepotinib (a highly selective MET TKI) plus gefitinib, compared with chemotherapy, particularly in patients with MET amplification. Here we present data at ≥18 months of follow-up.

      Method

      Asian patients with advanced, EGFR+, T790M-, MET+ NSCLC with resistance to prior EGFR TKIs were randomized to receive oral tepotinib 500 mg/day+gefitinib 250 mg/day or ≤6 cycles of cisplatin/carboplatin+pemetrexed chemotherapy±pemetrexed maintenance until confirmed progression, unacceptable toxicity, or withdrawal. Primary endpoint was investigator-assessed PFS. Secondary endpoints included ORR, overall survival (OS) and safety. Subgroup analyses were preplanned in MET IHC3+ and MET amplification populations (NCT01982955).

      Result

      Low recruitment halted full enrolment with 55 of 156 planned patients enrolled.

      As of 12-Dec-2018, median (range) duration of treatment with tepotinib+gefitinib was 21.4 (4.6, 110.9) weeks, with 3 patients still receiving treatment; and with pemetrexed was 18.0 (3.0, 60.4) weeks. 15 patients (62.5%) received ≥4 cisplatin/carboplatin cycles.

      Better outcomes were reported with tepotinib+gefitinib vs chemotherapy (Table), particularly in patients with MET IHC3+ (PFS: HR 0.35 [90% CI 0.17–0.74], OS: 0.32 [0.14–0.75]) or MET amplification (PFS: HR 0.13 [90% CI 0.04–0.43], OS: 0.08 [0.01–0.51]).

      Drug-related grade ≥3 adverse events (AEs) occurred in 17 (54.8%) patients receiving tepotinib+gefitinib and 12 (52.2%) patients receiving chemotherapy. Any-cause AEs leading to discontinuation occurred in 3 (9.7%) patients receiving tepotinib+gefitinib and 1 (4.3%) receiving chemotherapy. Dose reductions due to AEs were reported in 5 (16.1%) vs 4 (17.4%) patients.

      Conclusion

      Tepotinib+gefitinib has durable antitumor activity in patients with EGFR-mutant NSCLC with MET IHC3+ or MET amplification, and was generally well tolerated. MET amplification will be further explored as a biomarker for tepotinib.

      Table: Summary of efficacy data

      Population

      Tepotinib + gefitinib

      Chemotherapy

      HR/OR
      (90% CI)

      Overall MET+*

      Patients, n

      31

      24

      mPFS, months (90% CI)

      4.9 (3.9, 6.9)

      4.4 (4.2, 6.8)

      0.67 (0.35, 1.28)

      mOS, months (90% CI)

      17.3 (12.1, 37.3)

      18.7 (15.9, 20.7)

      0.67 (0.33, 1.37)

      ORR, n (%) [90% CI]

      14 (45.2) [29.7, 61.3]

      8 (33.3) [17.8, 52.1]

      1.99 (0.56, 6.87)

      MET IHC3+

      Patients, n

      19

      15

      mPFS, months (90% CI)

      8.3 (4.1, 21.2)

      4.4 (4.1, 6.8)

      0.35 (0.17, 0.74)

      mOS, months (90% CI)

      37.3 (24.2, 37.3)

      17.9 (12.0, 20.7)

      0.32 (0.14, 0.78)

      ORR, n (%) [90% CI]

      13 (68.4) [47.0, 85.3]

      5 (33.3) [14.2, 57.7]

      4.33 (1.03, 18.33)

      MET amplification

      Patients, n

      12

      7

      mPFS, months (90% CI)

      21.2 (8.3, NE)

      4.2 (1.4, 7.0)

      0.13 (0.04, 0.43)

      mOS, months (90% CI)

      37.3 (NE, NE)

      13.1 (3.3, NE)

      0.08 (0.01, 0.51)

      ORR, n (%) [90% CI]

      8 (66.7) [39.1, 87.7]

      3 (42.9) [12.9, 77.5]

      2.67 (0.37, 19.56)

      CEP-7, centromere protein 7; CI, confidence interval; EGFR, epidermal growth factor receptor; GCN, gene copy number; HR, hazard ratio; IHC, immunohistochemistry; IRC, independent review committee; ITT, intention to treat; MET, mesenchymal-epithelial transition factor; NE, not estimable; OR, odds ratio; ORR, objective response rate; OS, overall survival; PFS, progression-free survival

      All efficacy outcomes are investigator-assessed by RECIST v1.1.

      *IHC2+/IHC3+/gene amplification.

      MET amplification is defined as GCN ≥5 and/or MET/CEP-7 ratio ≥2. 17 of 19 patients with MET amplification have MET overexpression (IHC3+).

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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): Sang-we Kim

      • 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.

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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-51 - Next-Generation Sequencing for Effective Detection of Various EGFR Exon 20 Insertions (E20ins) in Non-Small Cell Lung Cancer (NSCLC) (ID 1750)

      10:15 - 18:15  |  Author(s): Sang-we Kim

      • Abstract

      Background

      Epidermal growth factor receptor (EGFR) E20ins are known as uncommon EGFR mutation and relatively insensitive to current EGFR tyrosine kinase inhibitors (TKIs). However, recent newer TKIs such as poziotinib show good clinical activity against them. Thus, we further explored the rate of EGFR E20ins and their clinical characteristics

      Method

      Between March 2017 and October 2018, 488 NSCLC tumor specimens were examined with OncoPanel AMC version3 which is a Next-generation sequencing (NGS) based assay for the detection of single-nucleotide variants, insertions, deletions, copy number alterations and structural variants across 382 genes. Peptide Nucleic Acid (PNA) clamping method version2 is to detect EGFR mutations using allele specific polymerase chain reaction and 6 variants of E20ins could be detected by it. We analyzed those NGS results and they were compared with PNA clamping method results if examined previously. Clinical characteristics were also reviewed.

      Result

      Among 488 patients, 143 showed EGFR mutations;16 patients showed wide variety of E20ins, while 59, 54 and 14 patients showing exon 19 deletion, L858R, and other rare EGFR mutations, respectively. Thus, the rate of E20ins was 11.2% of all EGFR mutations. For those 16 patients with E20ins, PNA clamping method failed to detect E20ins EGFR mutation in 8 patients (50%). Male/Female ratio was 7/9. Median age was 57 years (25-76 years). The rate of non-smoking was 68.8%. First-line platinum based regimen were given in 10 patients with 2.5 months of median progression free survival (PFS), while first-line EGFR TKIs were given in 5 patients with 2.3 months of median PFS. Poziotinib was provided to 2 patients later and they showed stable disease and partial remission.

      Conclusion

      EGFR E20ins were detected in 11.2% of EGFR-mutant NSCLC by OncoPanel AMC version3, and it was twice the rate by PNA clamping method. Clinically those patients showed lack of response to current EGFR TKIs. Poziotinib is a new EGFR TKI and promising for E20ins EGFR mutation.