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M. Fruh



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    MO06 - NSCLC - Chemotherapy I (ID 108)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO06.03 - Bevacizumab and erlotinib or bevacizumab, cisplatin and pemetrexed in patients with metastatic non-small cell lung cancer: EGFR mutation based treatment allocation and repeat biopsy at progression in the SAKK19/09 (BIOPRO) trial (ID 1862)

      16:15 - 17:45  |  Author(s): M. Fruh

      • Abstract
      • Presentation
      • Slides

      Background
      Treatment allocation by EGFR mutation and maintenance therapy are two new standards for patients (pts) with metastatic non-small cell lung cancer (NSCLC). This multicenter phase II trial (NCT01116219) for the first time prospectively tested pemetrexed and bevacizumab maintenance therapy in pts with EGFR wild type NSCLC, and included repeat biopsy at progression to study molecular mechanisms of drug resistance. Pts with EGFR mutation were treated with erlotinib and bevacizumab, based on the results of the previous SAKK19/05 trial.

      Methods
      100 pts were enrolled with metastatic nonsquamous NSCLC, sufficient material for mutation analysis and translational research, and consent to repeat biopsy at progression. Pts with EGFR wild type received 4 cycles of bevacizumab 7.5mg/kg, cisplatin 75mg/m2 (or carboplatin AUC5) and pemetrexed 500mg/m2 every 3 weeks, followed by maintenance therapy with bevacizumab and pemetrexed until progression. Pts with EGFR mutation received bevacizumab 7.5 mg/kg every 3 weeks and erlotinib 150 mg daily until progression. Pts were followed by CT-scan every 6 weeks and repeat biopsy was performed at progression. The primary endpoint was progression free survival (PFS) at 6 months. For an unpromising PFS at 6 months rate of ≤20% and a promising rate of ≥35%, 77 patients with EGFR wild type were needed to reach a power of 90% and an alpha level of 5%. Secondary endpoints were median PFS, overall survival (OS), best response rate of CR+PR (RECIST), and further biomarkers including KRAS, thymidylate synthase (TS), and multigene expression.

      Results
      Seventy-seven pts with EGFR wild type and 20 pts with EGFR mutation were evaluable, 3 pts were not evaluable. Pts on bevacizumab and chemotherapy received on average 9 cycles (range 1-25). No unexpected toxicities were observed. PFS at 6 months was 45.5% (CI: 34.1%, 57.2%), median PFS was 6.9 (CI: 4.6, 8.3) months, OS was 12.1 (CI: 8.7, 14.7) months, and best response rate of CR+PR was 62%. Sixteen pts remain on treatment. Repeat biopsy at progression was successful in 31 of 39 (79%) of patients on trial treatment, and except for one transient pneumothorax, no relevant complications occurred. KRAS mutation was associated with poor overall survival (HR 2.0, CI: 1.05, 3.88; P=0.03), but not with PFS or best response. Pts on bevacizumab and erlotinib received on average 16 cycles (range 6-37). PFS at 6 months was 70.0% (CI: 45.7%, 88.1%), median PFS was 14.0 (CI: 8.8, NA) months, median OS is not yet reached, best response rate of CR+PR was 70%, 11 pts remain on treatment. Further analysis of serial serum and tumor samples is ongoing.

      Conclusion
      Compared with the previous POINTBREAK trial of pemetrexed and bevacizumab maintenance in genetically unselected pts, this trial demonstrates almost identical survival rates in pts with EGFR wild type. KRAS mutation was prognostic, repeat biopsy at progression was feasible, and laboratory analysis is ongoing to validate TS and to develop a predictive gene signature. Firstline therapy with erlotinib and bevacizumab is promising in pts with EGFR mutation, and this combination is further tested in the ongoing ETOP 2-11 BELIEF trial.

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    P1.24 - Poster Session 1 - Clinical Care (ID 146)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P1.24-044 - Favorable Survival of Women with Non-Small Cell Lung Cancer (NSCLC) after Resection of Brain Metastases (BM) and Whole Brain Radiotherapy (WBRT) (ID 3092)

      09:30 - 16:30  |  Author(s): M. Fruh

      • Abstract

      Background
      In NSCLC, BM are found in 20%-50% overall and 10-18% at initial presentation. Average survival of these patients (pts) is only 3–6 months. The selection of pts who may benefit from surgical resection of BM is challenging. Our goal was to distinguish which pts might benefit from surgical resection of BM.

      Methods
      We retrospectively reviewed all pts receiving surgical resection of BM from NSCLC at our institution between 2000 and 2011. Survival after Brain surgery was measured.

      Results
      A total of 52 pts were identified. Median age was 59 years (35-81). ECOG Performance status was 2 or less in 88%.Only 2 were never smokers, and 94% smoked until < 5 years before diagnosis. Nineteen (37%) were women, 29 (56%) had adenocarcinoma (AC), 14 (27%) squamous cell carcinoma (SCC) and 9 (17%) not otherwise specified NSCLC. In 35 pts (67%) single BM was present, 2 in 6 (12%), 3 in 5 (9 %) and 4 or more in 3 (6%) pts. The stage of the primary lung tumor was T1-3 in 40 (78%) and N0-1 in 25 (48%). Synchronous BM were resected within one month of diagnosis in 29 (56%) pts. Twenty-three (44%) had no other distant metastases at the time of diagnosis of the BM. Distribution of distant metastases was adrenal (21%), liver (19%), bone (15%), lung (13%) and other (19%). Median time from lung cancer diagnosis to resection of BM was 7.5 months (0-63 months). WBRT was applied to 45 (87%) pts post brain surgery and once before surgery. The primary tumor was resected in curative intent in 14 (27%) pts at diagnosis. Thirty four (65%) received first line platinum chemotherapy doublets. Second line systemic therapy was given to 19 (37%) pts. Only 8 pts received tyrosine kinase inhibitors, but no one was treated for longer than 4 months. Eight are still alive. Median survival was 9.1 months with only one patient (initially pT2 pN0) surviving more over 5 years. One year survival was 42%. Median survival for males was significantly shorter (6.7 vs. 14 months [p<0.005]). AC was associated with improved survival compared to SCC (10.6 vs. 6.7 months [p<0.05]) with no correlation between gender and histology. In a multivariate analysis, the use of TKI, age and WBRT were not associated with outcome. Thirteen (25%) died within 3 months after surgery including 4 (8%) within 1 month. Six (46%) of them had other metastatic sites involved. New brain lesions post-surgery were documented in 12 (23%) and 4 (8%) had local progression at the resection site.

      Conclusion
      Resection of BM followed by WBRT lead to good local control. Despite patient selction with almost one third being treated with surgery of the primary tumor "curative intent" as well, only one patient lived > 5 years. The relatively high death rate (25%) within 3 months of surgery indicate the need for further research to better select patients suitable for survery. Female gender and AC histology were associated with better survival after resection of BM. These pts may preferably be considered for resection.