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S.I. Rothschild



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    Poster Display Session (ID 63)

    • Event: ELCC 2017
    • Type: Poster Display Session
    • Track:
    • Presentations: 3
    • Moderators:
    • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1
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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): S.I. Rothschild

      • 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.

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      112P_PR - Immune response and adverse events to influenza vaccine in cancer patients undergoing PD-1 blockade (ID 502)

      12:30 - 13:00  |  Author(s): S.I. Rothschild

      • Abstract

      Background:
      Immune checkpoint inhibitors have been introduced into standard clinical practice. Since cancer patients are at risk to develop complications when infected with seasonal influenza viruses – in particular patients with lung cancer that often have pre-existing lung disorders – it is recommended to vaccinate oncological patients. Concerns have been raised about the safety of influenza vaccination in patients undergoing checkpoint blockade. It is feared that immune stimulation via PD-1/PD-L1 blockade might induce an overshooting immune response.

      Methods:
      Patients undergoing checkpoint blockade were vaccinated with a trivalent influenza vaccination between October and November 2015. For an age-matched control cohort, the partners of the patients were vaccinated and included in our analysis as healthy controls. Safety and frequency of immune-related adverse events were evaluated. Antibody titers against antigens and strains that were included in the trivalent influenza vaccination were measured by hemagglutination inhibition assay in patients undergoing PD-1 blockade and age-matched controls. Cytokine/chemokine profile and changes in peripheral immune cells in a cohort of cancer patients undergoing immunotherapy with PD-1/PD-L1 blockade were also studies.

      Results:
      We included 23 patients at two institutions in Switzerland (University Hospital Basel and Cantonal Hospital Lucerne). Most patients have been treated with PD-1 blocking antibodies for at least 6 weeks at the time of vaccination. The frequency of irAEs was at 52.2% and 6 of 23 patients (26.1%) hat severe grade 3 or 4 irAEs. This frequency is significantly higher than in our general experience at our center (all grades 25.49%, grade 3 or 4 9.8%). There was no major difference over time in the generation of antibody titers in all three viral lines tested. Peripheral leukocyte counts and also cytokine/inflammatory chemokine levels did not change significantly shortly after vaccination.

      Conclusions:
      While the vaccination against seasonal influenza viruses seems to produce good serological protection and no short term toxicity of the vaccination could be observed, the increased rate of immunological toxicity is concerning and should be studied in a larger patient population.

      Clinical trial identification:


      Legal entity responsible for the study:
      N/A

      Funding:
      University Hospital Basel

      Disclosure:
      All authors have declared no conflicts of interest.

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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): S.I. Rothschild

      • 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.

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    Targeted therapies and immunotherapies (ID 46)

    • Event: ELCC 2017
    • Type: Poster Discussion session
    • Track:
    • Presentations: 1
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      91PD_PR - Response to salvage chemotherapy following exposure to PD-1/PD-L1 inhibitors in patients with NSCLC (ID 498)

      14:45 - 15:45  |  Author(s): S.I. Rothschild

      • Abstract

      Background:
      Immune checkpoint inhibitors are active for patients with stage IV NSCLC who have progressed following platinum-based chemotherapy. We evaluated responses to chemotherapy in patients with NSCLC who had progressed on a checkpoint inhibitor.

      Methods:
      Eligible patients were adults with NSCLC who received salvage chemotherapy following PD-1/PD-L1 inhibitors (cases) versus no PD-1/PD-L1 inhibitors (controls). CT-imaging was done within 4 weeks of initiation of salvage chemotherapy and every 6 weeks thereafter. Revised RECIST guidelines were used to define response. Clinical and imaging data were abstracted from review of electronic medical records. Multivariate logistic regression analysis was used to calculate probability of response.

      Results:
      355 patients’ charts were reviewed and 82 patients met eligibility criteria. Among evaluable patients, 46 were males versus 36 females. 67 patients were classified as cases versus 15 controls. 56 patients received nivolumab, 7 pembrolizumab and 4 atezolizumab. 63 (77%) patients had adenocarcinoma, 18 (22%) squamous cell carcinoma and 1 (1%) large cell carcinoma. The mean number of chemotherapy regimens prior to salvage chemotherapy was 2.37 (95% CI: 2.10-2.64) in cases versus 1.93 (95% CI: 1.32-2.54) in controls. Salvage drugs used included docetaxel (62%), pemetrexed (20%), gemcitabine (12%) and paclitaxel (6%). 18 (27%) cases had partial response to chemotherapy versus 1 (7%) controls. 15 (22%) cases had progressive disease versus 6 (40%) controls. 34 (51%) cases had stable disease versus 8 (53%) controls. The odds ratio for achieving a partial response was 0.30 (95% CI: 0.18 to 0.50, p = 0.000). In multiple logistic regression model, age, gender, number of prior chemotherapy regimens, tumor histology, smoking status, different salvage chemotherapy regimens were not associated with the likelihood of achieving a partial response.

      Conclusions:
      The odds of achieving a partial response to salvage chemotherapy were significantly higher in patients with prior exposure to PD-1/PD-L1 inhibitors. This observed difference however warrants confirmation in larger cohorts. Ongoing investigations include the duration of response as well as evaluation of toxicity.

      Clinical trial identification:


      Legal entity responsible for the study:
      N/A

      Funding:
      N/A

      Disclosure:
      All authors have declared no conflicts of interest.