Pneumologie 2016; 70 - P233
DOI: 10.1055/s-0036-1572237

Induction therapy with intercalated TKI and chemotherapy in NSCLC with activating EGFR mutation in stages II-IIIB: NeoIntercal

F Griesinger 1, M Sebastian 2, M Serke 3, C Grohé 4, L Hillejan 5, B Passlick 6, N Reinmuth 7, U Graeven 8, S Radke 9, A Karatas 10, M Tiemann 11, T Overbeck 12
  • 1Department of Hematology and Oncology, Pius-Hospital Oldenburg
  • 2Med. Klinik II, Dept. of Hematology and Oncology, University of Frankfurt
  • 3Pneumology III, Lungenfachklinik Hemer
  • 4Evangelische Lungenklinik Berlin
  • 5Dept. of Thoracic Surgery, Niels-Stensen-Kliniken Hospital St. Raphael Ostercappeln
  • 6Dept. of Thoracic Surgery, University of Freiburg
  • 7Lungenclinic Grosshandsdorf GmbH
  • 8Internal Medicine I, Kliniken Maria Hilf GmbH Mönchengladbach
  • 9Medical Affairs, Astrazeneca GmbH Wedel
  • 10Aio Ggmbh Berlin
  • 11Hematopathology Hamburg
  • 12Dept. of Hematology and Oncology, University of Goettingen

Introduction: EGFR TKI treatment is standard of care in patients with metastasized NSCLC carrying an activating EGFR mutation. 1st and 2nd generation agents lead to response rates of up to 70% in metastatic EGFRM+ NSCLC. Recently, new focus has been shed on intercalated regimens of chemotherapy and TKI showing improved PFS as well as OS in the metastatic setting in an unselected Asian population (Wu et al. 2013). 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 shown the feasibility and tolerability of an intercalated induction therapy concept (Lüers et al.). Study design: 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 center 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 platin 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 4th or 5th 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, the 2nd part of the study is planned to enroll an additional 27 patients. Secondary endpoints include OS, PFS, relapse rate, toxicity and feasibility. A liquid biopsy project is included in the study to correlate tumor biopsy results with liquid biopsy results. Furthermore, therapy effects will be monitored by liquid biopsy.