Author of

• 14409

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  P2.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 210)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Treatment of Localized Disease - NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 14443

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    P2.02-034 - Induction Therapy with Intercalated TKI and Chemotherapy in NSCLC with Activating EGFR Mutation in Stages II-IIIB: NeoIntercal (ID 2255)

    09:30 - 17:00  |  Author(s): N. Reinmuth
    • Abstract

    Background:
    EGFR TKI treatment is standard of care in patients with metastasized NSCLC carrying an activating EGFR mutation. 1[st] and 2[nd] generation agents lead to response rates of up to 70% in metastatic EGFRM+ NSCLC. Recently, new light has been shed on intercalated regimens of chemotherapy and TKI have shown improved PFS as well as OS in the metastatic setting in an unselected Asian population (Wu et al. 2013 The Lancet Oncology 14 (8): 777-86). Response is a predictor of PFS and OS in limited and locally advanced NSCLC. Chemotherapy induction alone leads to pCR rates of no more than 15%. No data have been generated for induction therapy including EGFR TKI in EGFRM+ NSCLC. Four cases treated in one center have demonstrated the feasibility and tolerability of an intercalated induction therapy concept (Lüers et al. 2013 Abstract WCLC).
    
    Methods:
    Therefore, NeoIntercal a single arm phase II study has been initiated in 9 centers in Germany. In a first step, patients with stage II to IIIB staged according to local standards will be screened for EGFR mutations by a ring certified pathologist. EGFRM+ patients will receive gefitinib 250 mg / die p.o. on d-12 to -1 (d1 = first day of first cycle of chemotherapy) followed by 3 cycles of taxane and platinum containing chemotherapy with intercalated gefitinib on d4-d20 of each cycle. After 2 cycles, restaging CT is performed and patients are scheduled to undergo surgery during the 4[th] or 5[th] week of the last cycle of CTx-gefitinib. Pathologic response rate is the primary endpoint. If more than 30% of patients achieve pCR (regression grades IIB and III according to Junker) in the mediastinal lymph nodes, it is planned to additionally enroll 28 patients in the 2[nd] part of the study. Secondary endpoints include OS, PFS, relapse rate and pattern, toxicity and feasibility. A liquid biopsy project is included in the study to correlate EGFR mutation status from tumor biopsy results with ctDNA plasma analysis. Furthermore, therapy effects will be monitored by liquid biopsy.
    
    Results:
    Study preparation and recruitment of clinical trial centers is nearly completed and the enrollment of the first patient is planned for 3Q2015. An interim analysis will be performed approximately 12 months after enrollment initiation with data from 21 patients. Should the interim analysis be positive and an additional 28 patients are included, the study is scheduled to end in approximately 2019 after a follow up period of 24 months.
    
    Conclusion:
    According to our knowledge, NeoIntercal is the first study in the neoadjuvant setting with curative intent applying an intercalating combination of chemotherapy and targeted therapy. The NeoIntercal study group believes that this study will potentially contribute to the improvement of EGFRM+ NSCLC therapy.