Pneumologie 2016; 70 - P132
DOI: 10.1055/s-0036-1572236

Intercalated TKI and chemotherapy induction in EGFR mt+ NSCLC stage IIIA and IIIB: report of 3 cases with complete pathologic remission in mediastinal lymph nodes

F Griesinger 1, A Lüers 1, M Falk 2, I Conradi 1, M Reinhardt 3, A Kluge 4, K Willborn 5, R Prenzel 6, DC Scriba 7, R Henke 8, W Eberhardt 9, C Hallas 2, M Tiemann 2
  • 1Department of Hematology and Oncology, Pius-Hospital Oldenburg
  • 2Hematopathology Hamburg
  • 3Nuclear Medicine, Pius-Hospital Oldenburg
  • 4Institute of Radiology, Pius-Hospital Oldenburg
  • 5Dept. of Radiotherapy, Pius-Hospital Oldenburg
  • 6Dept. of Pneumology, Pius-Hospital Oldenburg
  • 7Dept. of Thoracic Surgery, Pius-Hospital Oldenburg
  • 8Pathology Oldenburg
  • 9Dept. of Oncology, University of Duisburg-Essen

Background: EGFR TKI treatment is standard of care in patients with metastasized NSCLC carrying an activating EGFR mutation. However, induction concepts in locally advanced NSCLC with EGFR mutation have not been studied extensively. Recently new focus has been shed on intercalated regimens of chemotherapy and TKI, showing improved PFS as well as OS. This concept was used as induction regimen in 3 patients with activating EGFR mutation in stages IIIA and IIIB.

Methods: Patients were diagnosed according to standard imaging, histology and immunohistology methods. EGFR, KRAS, BRAF, ALK and P53 mutation analysis were performed. Remission induction was measured by RECIST 1.1, regression grading by Junker criteria.

Results: 2 female never smokers (pt#1/3) and 1 male light smoker (pt#2) (5 py) were diagnosed with adenocarcinoma of the lung, 2 with exon 21 L858R (#2,3) and 1 with Exon 19 deletion (#1). Tumor stage was T4 (extension to mediastinal pleura) N2M0 (#1), T2aN3 (#2) and T2N3M0 (#3). Induction therapy was started with erlotinib 150 mg/die p.o. days -12 to -1 (#1,2) and gefitinib (#3) in order to prove responsiveness of the tumor to EGFR-TKI. On day 0 partial response or no progression was achieved in all 3 patients. Therapy was continued with 3 cycles of docetaxel 75 mg/m2 d1 and cisplatin 50 mg/m2 d1 and 2 qd22 in combination with erlotinib d4 – 19 (#1), 1 cycle of docetaxel and cisplatin followed by 2 cycles of paclitaxel and carboplatin and switch from erlotinib to gefitinib with cycle 2 (#2) because of diarrhea and 3 cycles of docetaxel and cisplatin with gefinitib 250 mg d4 – 19 (#3). PR was achieved after 2 cycles in all patients. All three patients were resected and regression grade IIB was remarked in mediastinal lymph nodes (#1 – 3), regression IIA was remarked in the primary tumor in 2 patients (#2,3), regression grade III in 1 patient (#1). All three patients received adjuvant radiotherapy. Patients #1 and 3 are in CR, patient 2 developed one isolated CNS metastasis. Conclusion: Intercalated TKI treatment is a promising treatment choice in patients with EGFR mt+ locally advanced NSCLC. A phase II trial (NeoIntercal) trial is currently under way in 9 German centers in stages II and III using gefitinib in combination with induction taxane based chemotherapy, supported by ASTRA Zeneca.