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C. Hallas



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    MINI 05 - EGFR Mutant Lung Cancer 1 (ID 103)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      MINI05.03 - P53 Disruptive Mutation Is a Negative Predictive Factor in EGFR M+ NSCLC Treated with TKI (ID 903)

      16:55 - 17:00  |  Author(s): C. Hallas

      • Abstract
      • Presentation
      • Slides

      Background:
      p53 mutations are common in lung cancer, and have also been described in EGFR mutated patients. The impact of p53 mutations in EGFR M+ patients is controversial, especially if classified as “disruptive” and “non-disruptive” according to their functional effect on the p53 protein as proposed by Poeta and colleagues. The aim of the study was therefore to systematically analyze EGFR and p53 mutations within a cohort of patients with lung cancer stage IV (UICC 7), to correlate alterations with clinical characteristics and to investigate a potential impact of p53 mutations on treatment outcome.

      Methods:
      267 patients from a single center diagnosed with lung cancer stage IV were studied for the presence of EGFR as well as inactivating p53 mutations. Methods for the detection of EGFR mutations included Sanger Sequencing and hybridization based COBAS testing. P53 mutations were detected by Sanger Sequencing. Clinical characteristics including smoking status were available for all patients.

      Results:
      267 consecutive patients at the lung cancer center of the Pius-Hospital Oldenburg were studied. The overall EGFR mutation rate was 19% (51/267) in all patients, 80% (41/51) showing common mutations of exon 19 or 21. P53 disruptive mutation showed in 16% (8/51) and p53 nondisruptive mutation occurred in 11% (22/51) whereas p53 WT was found in 47% (24/51). In 8/51 (16%) patients p53 analysis was not successful. OS was 37 months in p53 disruptive mutation and p53 WT patients compared to 19 months in p53 nondisruptive mutation (p<0,05). PFS on 1st line TKI therapy was 18 months in p53 nondisruptive mutation and p53 WT patients and 6 months in p53 disruptive mutation (p<0,024). Similar results could be shown in the EGFR common mutation subgroup but not in the uncommon mutation subgroup.

      Conclusion:
      Significant differences in PFS and OS in EGFR M+ patients were observed depending on p53 mutation status. P53 mutational status is only predictive when disruptive and non-disruptive P53 mutations are differentiated. P53 should be tested prospectively in EGFR M+ patients as management of patients on 1st line TKI may be different.

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    P3.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 214)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      P3.03-018 - Intercalated TKI and Chemotherapy Induction in EGFR mt+ NSCLC Stage IIIA and IIIB: 3 Cases with Complete Remission in Mediastinal Lymph Nodes (ID 3223)

      09:30 - 09:30  |  Author(s): C. Hallas

      • Abstract
      • Slides

      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 3 patients with activating EGFR mutation in stages IIIA and IIIB.

      Methods:
      Patients were diagnosed and worked up according to standard imaging, histology and immunohistology methods. EGFR, KRAS, BRAF, ALK and P53 mutation analysis were performed with standard procedures as described by Halbfass et al. 2013. Remission induction was measured by RECIST 1.1, regression grading by Junker criteria.

      Results:
      2 female never smokers (pt #1 and 3), 62 and 59 y.o. and 1 male light smoker (pt#2) (5 packyear), 58 y.o . were diagnosed with with TTF1+ adenocarcinoma of the lung, 2 with exon 21 L858R (#2,3) and 1 with Exon 19 deletion (#1). All patients carried a p53 mutation, exon 6 (#2,3), exon 8 (#1). Tumor stage was T (extension to mediastinal pleura) N2 (2R, 4R) M0, IIIA4 (#1), T2aN3(4L,7,2R)M0 IIIB (#2) and T2N3M0. 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 (#2) 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 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 which has been stereotactically irradiated. No additional therapy, including TKI was administered postoperatively.

      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.

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