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R.P. Henke



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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-035 - Acquired resistance in NSCLC with EGFR mutation treated with TKI's: Single center experience and treatment outcome (ID 2633)

      09:30 - 09:30  |  Author(s): R.P. Henke

      • Abstract

      Background
      Acquired resistance in NSCLC with activating EGFR mutations has been defined by Jackman et al. The molecular mechanisms have been studied in small series of patients: in about 50% of cases, T790M mutation confers acquired resistance, in 25% c-Met overexpression detected by IHC. Other as of yet unknown mechanisms might also play a role. Here we present the acquired resistance mechanisms in a cohort of 12 patients (out of 33 pts.) with activating EGFR mutations treated with TKI and identified at our center (see Halbfass et al.). Treatment methods and outcome are also described

      Methods
      159 consecutive patients (s. abstract Halbfass et al.) were molecularly studied for EGFR mutations in exons 18-21. EGFR mutation analysis was performed by Sanger Sequencing or by hybridization based COBAS methodology after microdissection of tumor tissue to ascertain a high percentage of tumor tissue. c-Met IHC was performed automatized by standard procedure (BondMax, Menarini). ALK rearrangement was studied using a break apart FISH-Probe (Abbott). Remission was measured by RECIST 1.1 criteria.

      Results
      Of 159 patients tested, 33 had an EGFR mutation, of which 3 had primary resistance mutations (T790M 1 case, Exon 20 insertions 2 cases). Of these 30 pts., 20 had acquired resistance and 12 were rebiopsied. 8 were not rebiopsied for various reasons, the most common being progress in the CNS. Of the 12 rebiopsied pts, c-Met was successfully studied in 8, T790M in 12 and ALK in 6. In 5/8 pts., c-Met was amplified, in 4/12 pts. the T790M mutation was found and in 1/6 pts., an ALK rearrangement was observed. 4 pts. received afatinib, 2 pts. chemotherapy, 2 pts. afatinib and cetuximab, 1 pt. afatinib and crizotinib and 2 pts. other treatments. Detailed treatment results will be presented at the meeting.

      Conclusion
      The understanding of resistance mechanisms in acquired TKI resistance is of academic interest and might be important for subsequent treatment options. Therefore, rebiopsy at progress while on TKI therapy should be discussed with patients. As targeted treatment options are available for c-Met, ALK as well as T790M, resistance mechanisms potentially may guide therapeutic strategies in EGFR mutated patients with acquired resistance.

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    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.10-028 - Pathologic complete remission after induction chemotherapy and intercalated Erlotinib in EGFR-mutated adenocarcinoma stage IIIA: Case report. (ID 1784)

      09:30 - 09:30  |  Author(s): R.P. Henke

      • Abstract

      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 including TKI 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 a female patient with activating EGFR mutation as well as p53 mutation and stage IIIA 3 multilevel.

      Methods
      Patient was diagnosed and worked up according to standard imaging, histology and immunohistology methods. EGFR, KRAS, BRAF, ALK and P53 mutation analysis was performed as described by Halbfass et al. Remission induction was measured by RECIST 1.1, regression grading by Junker criteria.

      Results
      A female caucasian 62 y.o. never smoker was diagnosed with TTF1+ adenocarcinoma G3 of the upper lobe of the lung, c2T3 (extension to mediastinal pleura) c2N2 (LN 2R and 4R) c2M0, UICC7 IIIA4 (Robinson). Molecular analysis after microdissection revealed WT for ALK, KRAS and BRAF, but an activating EGFR mutation Exon19 (p.Leu747_Ala750delinsPro), as well as a TP53 mutation in exon 8 (p.Val272Met (c.814G>A) (Sanger Sequencing). Induction therapy was started with erlotinib 150 mg/die p.o. days -12 to -2 in order to prove responsiveness of the tumour to TKI. On day 0 partial response was achieved. Therapy was continued with 3 cycles of Docetaxel 75 mg/m2 d1 and Cisplatin 50 mg/m2 d 1 and 2 qd22 with intercalated Erlotinib 150 mg/die p.o on days 4-19. Almost complete radiologic remission was achieved after 2 cycles The patient underwent R0 resection (upper lobe resection and radical lymphadenectomy) 4 weeks after day 1 of the 3[rd] cycle of chemotherapy, pathologic examination revealed T0N0 (mic+) with only one insula of tumor cells in an N2 lymph node, demonstrating regression grade III in the primary tumor and Grade IIB in the lymph nodes, according to the Junker classification. Molecular analysis of residual tumor cell insula revealed the same EGFR and p53 mutations as the primary tumour. The patient underwent postoperative radiotherapy of the mediastinum. No additional therapy, including TKI was administered postoperatively.

      Conclusion
      Intercalated TKI treatment might be a promising treatment choice in patients with EGFR mutated locally advanced NSCLC. A phase II trial is currently being planned to expand knowledge in this challenging field.