Author of

• 20039

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  Poster Display Session (ID 63)

  • Event: ELCC 2017
  • Type: Poster Display Session
  • Track:
  • Presentations: 2
  • Moderators:
  • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1

  • 19866

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    110P - Afatinib for patients with advanced NSCLC pretreated with chemotherapy and an EGFR tyrosine kinase inhibitor: Retrospective analysis of the Swiss Afatinib Named Patient Program (ID 505)

    12:30 - 13:00  |  Author(s): M. Früh
    • Abstract

    Background:
    Epidermal growth factor receptor (EGFR) mutations are found in 12-15% of lung adenocarcinoma patients in European countries. Afatinib is a second-generation EGFR tyrosine kinase inhibitor (TKI) and is approved for stage IV NSCLC patients with common EGFR mutations. Based on the LUX-Lung 1 trial a named patient program for afatinib was initiated in Switzerland. We thus aimed to evaluate afatinib activity in patients which where previous treated with chemotherapy and first-generation TKIs.
    
    Methods:
    This multicentre retrospective analysis was performed in 11 institutions in Switzerland. We reviewed clinical records of patients included in the afatinib NPP.
    
    Results:
    Between 03/2011 and 04/2014 a total of 69 patients were included in the NPP. Baseline characteristics were obtained from all these patients. Follow-up data were accessible from 41 patients. Median age of the population was 63 years (range, 46-79). 68% of patients were female and 28% were never smoker. Adenocarcinoma was the predominant histological subtype (93%). 56 patients (81%) had a proven EGFR mutation. Of those, 29 patients (52%) had a deletion 19, 16 patients (29%) had a L858R mutation in exon 21. A T790M mutation was detected in 10 patients (18%). 50 patients (73%) received treatment with erlotinib and 14 patients (20%) with gefitinib before inclusion in the NPP. 31 patients were evaluable for response assessment by RECIST 1.1. One patient (3.2%) achieved a complete remission, 4 patients (12.9%) showed a partial remission and 3 patients (9.7%) disease stabilization. Mean duration of afatinib therapy was 200 days (95% CI 146-255). Mean overall survival (OS) from diagnosis of metastatic NSCLC was 17.2 months (95%CI 11.9-22.6). In multivariate analysis, EGFR mutation was associated with response to afatinib.
    
    Conclusions:
    This study confirms the activity of afatinib in pretreated lung adenocarcinoma. The benefit is larger in patients with EGFR mutation positive tumors and mainly in those with classical mutations (deletion 19 or point mutation L858R in exon 21).
    
    Clinical trial identification:
    
    
    Legal entity responsible for the study:
    N/A
    
    Funding:
    Unrestricted educational grant by Boehringer-Ingelheim
    
    Disclosure:
    S.I. Rothschild: Advisory Board Boehringer-Ingelheim (honorary paid to the institution). All other authors have declared no conflicts of interest.
    
    

  • 19808

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    31P - Targeted therapy for patients with ALK positive NSCLC: Results from the transalpine cohort (ID 332)

    12:30 - 13:00  |  Author(s): M. Früh
    • Abstract

    Background:
    Anaplastic lymphoma kinase (ALK) rearrangements occur in 3-5% of lung adenocarcinoma. ALK tyrosine kinase inhibitors (ALK-TKIs) are used for the treatment of these patients as standard of care, in clinical trials or in expanded access programs. The aim of this study was to analyze the clinical characteristics of response and progression to different ALK-TKIs and to study mechanisms of resistance using next generation sequencing (NGS).
    
    Methods:
    This collaborative study was performed in five institutions in Switzerland and Italy. Clinical data from patients diagnosed with ALK positive NSCLC (i.e. break in 2p23 in FISH) in the palliative setting were collected and analyzed. If available, biopsies both before starting ALK-TKI and at progression were subjected to NGS using the Ion AmpliSeq Comprehensive Cancer Panel.
    
    Results:
    We collected clinical data of 139 patients. 117 have so far undergone first-line treatment with chemotherapy (ChT) (n = 87, 74%), ALK-TKIs (n = 29, 25%) or other (n = 1, 1%). Second-line therapy was given in 92 patients; 16 received ChT (17%), 68 ALK-TKIs (74%), 8 immuno- (I-O) and other therapies (9%). 55 patients underwent third-line therapy comprising ChT (n = 11, 20%), ALK-TKIs (n = 40, 75%), or I-O and others (n = 3, 5%). Fourth-line treatment was given to 24 patients; ChT (n = 8, 33%), ALK-TKIs (n = 15, 63%) and other treatments (n = 1, 4%). 11 patients have received five or more lines of therapy. Crizotinib was given to 102 patients (81% in first- or second-line) resulting in a median PFS of 11.7 months (95% confidence interval [CI] 8.2-13.1). Ceritinib was given to 37 patients (76% in third- or later line) with a median PFS of 6.5 months (95% CI 3.7-9.4). 26 patients received alectinib (85% in third- or later line) with a median PFS of 12.4 months (95% CI 8.4-17.0). So far, NGS has been performed in 5 patients before and after ALK-TKI therapy. Two secondary ALK mutations were detected (ALK p.I1171S and p.C1156Y) conferring responsiveness to further ALK-TKIs.
    
    Conclusions:
    This study confirms the activity of ALK-TKIs in ALK positive NSCLC and allowed the documentation of important clinical data in the real-life setting. Moreover, an in-depth molecular analysis of resistance mechanisms was performed, which will now be expanded to more patients from the cohort.
    
    Clinical trial identification:
    
    
    Legal entity responsible for the study:
    University Hospital Zurich
    
    Funding:
    University Hospital Zurich, Novartis
    
    Disclosure:
    S.I. Rothschild: Compensation (to the institution) for advisory boards from Novartis, Pfizer and Roche. Compensation (to the institution) for invited talks from Pfizer and Roche. All other authors have declared no conflicts of interest.