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O. Gautschi
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Poster Display Session (ID 63)
- Event: ELCC 2017
- Type: Poster Display Session
- Track:
- Presentations: 4
- 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): O. Gautschi
- 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): O. Gautschi
- 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): O. Gautschi
- 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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7P - Population-level effect of targeted therapy in patients with advanced pulmonary adenocarcinoma: A Swiss prospective cohort study (ID 453)
12:30 - 13:00 | Author(s): O. Gautschi
- Abstract
Background:
Large cancer centres in the USA demonstrated that molecular diagnosis and targeted therapy improved overall survival (OS) of patients with advanced pulmonary adenocarcinoma (Kris, JAMA 2014). We validated this finding in a rural area of Switzerland, served by private practices, community hospitals, and a tertiary referral centre.
Methods:
We conducted a prospective cohort study with the Cancer Registry of Central Switzerland, established in 2010, covering 4 cantons and 517'000 inhabitants. We enrolled all residents newly diagnosed with stage IV pulmonary adenocarcinoma from 2010 until 2014. From the registry, the central pathology and the residents’ offices, we obtained the date of diagnosis and death, gender, smoking, tumour histology and stage, molecular testing (on demand), and therapy. We used the Kaplan-Meier method and a log-rank test to compare OS, and Cox proportional hazards model for association with age, gender and smoking. The cutoff date was February 2016. No adjustment was made for multiple testing. The study was approved by the IRB.
Results:
348 patients were included in the study. Median age at diagnosis was 66 years (range, 30-94), 190 (55%) patients were men, 197 (57%) were smokers or former smokers. Molecular testing (PCR, IHC and FISH) was performed in 279 (80%), 132 (38%) had oncogenic driver mutations (ODM): KRAS (17%), EGFR (12%), ALK (6%), HER2 (2%), BRAF (1%), RET (0,5%) or MET (0,5%). 56 patients with an ODM, mostly EGFR (34) and ALK (12), received genotype-matched targeted therapy, at least 25 (45%) of whom in a clinical trial or named patient program. Median OS was 18 months for patients with ODM and targeted therapy, 8 months for patients with ODM and conventional therapy, and 10 months for patients with no ODM and conventional therapy. For patients with ODM and targeted therapy, OS was significantly better than for patients with ODM and conventional therapy (HR 0.64, p = 0.04).
Conclusions:
Rigorous testing combined with optimal access to targeted therapy in clinical trials, improved the prognosis of patients with advanced pulmonary adenocarcinoma and EGFR mutation or ALK rearrangement. For patients with tumours lacking actionable mutations, further advances are expected with immunotherapy.
Clinical trial identification:
Legal entity responsible for the study:
J. Diebold, Institute of Pathology, Cantonal Hospital Lucerne, Lucerne, Switzerland
Funding:
Cancer League of Central Switzerland, Lucerne, Switzerland
Disclosure:
All authors have declared no conflicts of interest.
