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

  • 19860

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    104P - Efficacy of ceritinib in a "real-world" population of crizotinib-refractory ALK-positive NSCLCs: Results of the Italian compassionate use program (ID 422)

    12:30 - 13:00  |  Author(s): G. Metro
    • Abstract

    Background:
    Ceritinib has been approved by EMA for the treatment of patients (pts) with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) who progress on crizotinib. Nevertheless, this drug is not reimbursed in Italy by the National Health Care System as of January 2017. The aim of this study was to assess the efficacy of ceritinib administered within a compassionate use (CU) program made available to crizotinib-refractory patients.
    
    Methods:
    This collaborative study involved multiple institutions in Italy. Clinical data from crizotinib-refractory pts with ALK-positive NSCLC who were requested ceritinib compassionate use (CU) were collected and analyzed.
    
    Results:
    Twenty-four centres took part to the study, for a total of 70 pts who were requested ceritinib CU. Of these, 63 pts received at least one dose of ceritinib 750 mg/d from July 2014 to January 2017. Pts characteristics were as follows: median age 56 years (22-86), 34/63 (54%) female, 43/63 (68%) never smokers, 12/63 (19%) ECOG PS ≥ 2, 13/63 (21%) pretreated with ≥ 2 lines of chemotherapy, 49/63 (78%) metastatic to the brain. Median time on prior crizotinib was 370 days (51-1644). The most common any grade treatment-related adverse events (TRAEs) were nausea (60%, 6% grade 3 or 4), vomiting (49%, 5% grade 3 or 4), diarrhea (51% 2% grade 3 or 4), ALT elevation (48%, 17% grade 3 or 4), AST elevation (49%, 17% grade 3 or 4), and fatigue (59%, 8% grade 3 or 4). Dose reduction due to TRAEs occurred in 31/63 pts (49%). Out of 31 pts, 15 pts (49%) reduced the dose to 600 mg/d, 10 pts (32%) to 450 mg/d, and 6 pts (19%) to 300 mg/d. Unusual TRAEs consisted of an increase in serum creatinine in 3 pts. Of the 55 patients who were evaluable for response, 21 pts (38%) responded to treatment. Overall, at a median follow-up of 6.2 months (0.5-26), median progression-free survival (PFS) was 7.6 months and 6-month PFS was 59%.
    
    Conclusions:
    The ceritinib CU program in Italy confirms the efficacy of the drug in a "real-world" setting, with a safety profile that is similar to that observed in clinical trials. A high rate of dose adjustments due to TRAEs was observed, which, however, did not appear to influence the activity of the drug.
    
    Clinical trial identification:
    NA
    
    Legal entity responsible for the study:
    N/A
    
    Funding:
    Associazione Italiana per la Ricerca contro il Cancro
    
    Disclosure:
    All 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): G. Metro
    • 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.