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A. Tamiya



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    MINI 16 - EGFR Mutant Lung Cancer 2 (ID 130)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      MINI16.01 - Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment Response in Advanced Non-Small Cell Lung Cancer With Uncommon Mutations (ID 1170)

      16:45 - 16:50  |  Author(s): A. Tamiya

      • Abstract
      • Presentation
      • Slides

      Background:
      Treatment of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is the standard therapy for advanced non-small cell lung cancer (NSCLC) with common EGFR mutations such as exon 19 deletions or L858R mutations. However, the efficacy of EGFR-TKIs in patients with uncommon EGFR mutations remains unclear.

      Methods:
      We have retrospectively surveyed a consecutive database of NSCLC patients with EGFR mutations at Kinki-chuo Chest Medical Center, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases. We analyzed the collect data of NSCLC patients with uncommon mutations including single or complex (uncommon plus uncommon mutations, or uncommon plus common mutations) mutations, treated with gefitinib or erlotinib between July 2007 and September 2014.

      Results:
      Forty-one patients who had any EGFR uncommon mutations were analyzed in this study. By the Response Evaluation Criteria in Solid Tumors criteria, the overall response rate (RR) was 22.0% with 9 partial response (PR) in all patients with uncommon mutations. Among uncommon single mutations, RR was 12.5% with 3 PR in patients with G719X mutation and 33.3% with 2 PR in patients with L861Q mutation. As for complex mutations, there were no patients in PR with uncommon plus uncommon mutations but RR was 50.0% with 4 PR in patients with uncommon plus common mutations. Median progression-free survival (PFS) was 3.5 months in all patients with uncommon mutations. Among uncommon single mutations, PFS in patients with G719X (median PFS: 1.8 months) was shorter than PFS in patients with L861Q mutation (median PFS: 7.6 months). Furthermore, there was a difference in the efficacy of EGFR-TKIs among patients with each G719X mutation (median PFS in G719A: 8.2 months, median PFS in G719C: 1.1 months, median PFS in G719S: 1.7 months).Figure 1



      Conclusion:
      First generation EGFR-TKIs are less effective in NSCLC patients with uncommon mutations than in those with common mutations. However, they had favorable response in patients with L861Q or G719A mutations, compared with G719C or G719S mutations.

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    P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P1.01-004 - Updated Results and Efficacy Analysis According to EGFR Mutation Subtypes for Gefitinib plus Carboplatin and S-1 of the Phase II Trial (ID 765)

      09:30 - 09:30  |  Author(s): A. Tamiya

      • Abstract
      • Slides

      Background:
      Good efficacy and survival was observed in patients with advanced non-small cell lung cancer harboring epidermal growth factor receptor (EGFR) mutation. And the phase II study treated with gefitinib plus carboplatin and S-1 previously demonstrated the good efficacy in terms of progression free survival (PFS) and response rate (RR) as the first-line treatment of advanced NSCLC harboring activating EGFR mutations.

      Methods:
      This trial was multi-center, open rabel, single arm trial. All patients had a dvanced non-small cell lung cancer (Stage IIIB / IV) harboring activating mutations.A total of 35 patients received carboplatin on day 1 plus oral S-1 on days 1–14 and gefitinib daily. Updated results and subgroup analysis according to EGFR mutations are presented.

      Results:
      All patients had lung adenocarcinoma with activating EGFR mutations, namely, deletion (exon 19; n = 22), L858R (exon 21; n = 12), and T790M/L858R (exons 20 and 21; n = 1). Almost all patients had stage IV disease. The updated analysis revealed response rate of 85.7 %, a median PFS of 17.6 months (95% CI: 13.4 - 23.0 months), and a median overall survival (OS) was not reached (95% CI: 27.8 months -). Response rate and median PFS and median OS were 90.9 %, 18.7 months (95% CI: 15.5 - 28.4 months) and not reached (95% CI: 27.8 months -) in the exon 19 del+ arm, and 83.3 %, 13.4 months (95% CI: 6.2 - 18.5 months), and 27.9 months (95% CI: 10.1 - 32.4 months) in the exon 21 (L858R) arm. The common toxicities related to gefitinib were skin rash, elevated transaminase and diarrhea. And the common toxicity in the present trial was neutropenia. No interstitial lung disease or treatment-related deaths occurred.

      Conclusion:
      This triplet chemotherapy showed good efficacy and prolonged PFS. And this analysis showed the different efficacy in terms of PFS and OS of gefitinib plus carboplatin plus S-1 in patients with advanced NSCLC between EGFR mutation subtypes.

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