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7517 Background: Tumor cells expressing programmed cell death 1 ligand (PD-L1) are believed to suppress immune responses through activation of the PD-1/PD-L1 pathway. Recent data indicate that PD-L...

e18505 Background: Adjuvant chemotherapy is the standard treatment for early stage non-small-cell lung cancer (NSCLC) patients after complete resection. The most evidence-based data exist for the c...

CRA10529 Background: Personalized treatment of genetically stratified subgroups has the potential to substantially improve outcome in NSCLC. A major challenge now is to implement high-quality molecular diagnostics and personalized treatment strategies in routine clinical practice also outside of highly specialized academic centers. Methods: We have established a molecular screening network in the catchment area of our comprehensive cancer center encompassing about 2.5 million inhabitants in March 2010 after review of the local ethics committee (10-242). Lung adenocarcinoma (AD) was screened centrally for ALK translocations, mutations in KRAS, EGFR, BRAF and PIK3CA and for amplification of ERBB2. Squamous cell carcinoma (SQ) was analyzed for FGFR1 amplifications. Results: 2032 NSCLC samples were acquired of which 1782 in the Cologne-Bonn area indicating a capture rate of 60-70% of all NSCLC samples in the area. Material was suitable for molecular analysis in 77%. Distribution of histological subtypes was as expected (AD 63.4%, SQ 26.7, large cell carcinoma 1.4%, adenosquamous cell carcinoma 1.8%, carcinoid 0.1%, NSCLC NOS 6.7%. In AD the following frequencies of genetic lesions were detected: KRAS (32%), EGFR (13%), ALK (3%), BRAF (2%), PIK3CA (2%), ERBB2 (2%). EGFR mutations were highly enriched in the lepidic and micropapillary subtype of AD (30-32%), whereas the solid subtype only harboured a very small amount of the tested oncogenic lesions. In SQ FGFR1 amplification was detected in 78/500. Overall 40% of all NSCLC samples harboured potentially tractable oncogenic lesions. All patients with ALK translocations received crizotinib when clinically indicated. 75% of the stage IIIB/IV patients with activating EGFR mutations received EGFR-TKI treatment. In addition, clinical trials have been initiated to provide personalized treatment options to all patients with tractable genetic lesions. Conclusions: High-quality molecular diagnostics and identification of patients for personalized treatment approaches is feasible in daily clinical routine for the majority of diagnostic samples also in a non-academic setting.

7603 Background: Since the introduction of targeted therapy into the treatment of NSCLC, molecular imaging tools gain in importance for assessment of pharmacodynamics, pharmacokinetics and prediction of therapeutic outcome. Tumor metabolism (by FDG-PET), proliferation (by FLT-PET), and vascularization (by DCE-MRI) can be noninvasively assessed to quantify the effects of targeted therapy on tumor biology. We set up a trial to evaluate the effects of combined erlotinib (E) and bevacizumab (B) treatment in patients with advanced non-squamous cell NSCLC and to identify prospectively patients who benefit from this combination. Methods: Patients with non-squamous NSCLC stage IV without prior systemic therapy received at least six weeks of combined E and B. FLT and FDG-PET scans as well as DCE-MRI-scans were performed at baseline, after 1 week of therapy and after 6 weeks of therapy. Standard uptake values of the PET scans and vascularization parameters of the DCE-MRI scans were analyzed and coregistrated. Tumor specimens were analysed within a network screening panel. The primary objective of this trial was to evaluate the accuracy of the imaging tools for early prediction of nonprogression and PFS and its association with molecular markers. Results: Of the 40 patients, all received FDG-PET analyses, whereas FLT-PET was performed in 38 patients and DCE-MRI in 36 patients. Median OS was 13.4 months, median PFS was 5.9 months. Until January 2012, tissue specimens from 25 patients have been genetically analysed. First results show that even patients with KRAS, PI3K and BRAF mutations profiting from the combination either by response or prolonged PFS could be identified by early imaging assessment. Conclusions: The efficacy of E +B in unselected patients with NSCLC was comparable with platinum-based chemotherapy. In order to identify imaging-based predictive biomarkers to identify the subpopulation of patients with pronounced benefit of this combination FDG-, FLT- PET and DCE–MRI were successfully implemented in the treatment plan. Results of the imaging analysis and the correlation with tissue-based biomarkers will be presented.

10526 Background: PIK3CA mutations are a rare oncogenic event of potential therapeutic relevance in NSCLC. Here we report frequency and characteristics of patients with PIK3CA mutated lung tumors. Methods: Patients with NSCLC and PIK3CA mutations were identified within our regional Network for Molecular Screening in Lung Cancer. We further analyzed the presence of BRAF, KRAS, EGFR mutations as well as ALK translocation, ERBB2 and FGFR1 amplifications in PIK3CA mutated samples. Clinical data on age, sex, TNM classification and tumor stage, histological type, grading, overall survival, smoking status, comorbidity, BMI and secondary malignancies were retrieved from clinical charts in accordance with the local ethics committee. Results: PIK3CA mutations were detected with a frequency of 3.7% (24% exon 20,76% exon 9) in 1000 patients. Histologically 32% were defined as squamous cell carcinoma, 48% as adenocarcinoma and 18% other histological subtypes or NSCLC-NOS. Exon 9 mutations were present in the acinar and lepidic subtype, whereas exon 20 mutations were seen in the papillary and solid subtype. Cooccuring genetic lesions were observed in 16% (mutations in KRAS=2, EGFR=1, BRAF=1; FGFR1 amplification=2). 14 were female, 23 male with a mean age of 69 years. 21 of these patients were further clinically annotated. 11 patients presented with stage IIIb/IV eligible for palliative treatment and 10 stage I – IIIa eligible for surgical therapy +/- adjuvant therapy. All but 1 patient were smokers with an average BMI of 26,2kg/m2 with a typical high load of comorbidity mainly of cardiovascular diseases, 8 of 21 patients showed prior malignancies in their medical history. The median overall survival within this population has not been reached yet. Conclusions: Screening for PIK3CA mutations is feasible. A high proportion (38%) of patients with PIK3CA mutated lung cancer have prior malignancies and show a high load of comorbidity. Furthermore PIK3CA mutations are not exclusive to KRAS, EGFR or BRAF mutations or FGFR1 amplifications. Successful identification of patients with oncogenic lesions in lung cancer in a screening network might allow future personalized treatment of these patients.

e18000 Background: Phospatidylinositol-3-kinases (PI3K) play an important role in various cell processes. Oncogenic mutations in the PIK3CA gene which codes for the catalytic subunit have been identified in various malignancies and activate the PI3K/AKT/mTOR pathway which is a critical driver of tumorigenesis. Methods: We tested 41 tumor samples with known KRAS, BRAF, and EGFR mutation status for the occurence of mutations in the PIK3CA gene using a new commercial pyrosequencing kit. Results: Pyrosequencing revealed 2 mutations (4.9 %) in the PIK3CA gene, one in exon 9 and one in exon 20. Both mutations have not yet been identified in lung tumor tissue. Conclusions: The screening of our small patient cohort by pyrosequencing identified two mutations (4.8 %) in PIK3CA, on in exon 9 (Q546H) and on in exon 20 (M1043T). Both mutations have not yet been described in lung tumours and seem to be rather uncommon mutations. Future Screening of large patient cohorts with pyrosequencing may contribute to the detection of more mutations in lung cancer due to the low limit of detections of this method and may contribute to a better understanding of the interaction of mutations and tumorigenesis.

1533 Background: FGFR1 amplifications have been described as a promising oncogenic target in squamous cell lung cancer. Here we aimed at describing the clinical characteristics and natural history of FGFR1amplified squamous cell lung cancer patients. Methods: From 01/2011 to 01/2012 we screened 553 squamous cell lung cancer patients in our Network for Molecular Screening of Lung Cancer for the presence of FGFR1 amplifications by FISH analysis in accordance with the local ethics committee. FGFR1 was defined as amplified if the ratio of FGFR1 copies to centromeric copies was above 2 or if more than 50% of tumor cells showed 5 copies or if more than 15% of tumor cells demonstrated clusters of FGFR1. Clinical data were collected by extracting information from medical records, the local cancer registry and by questioning treating physicians and patients. Results: FGFR1FISH analysis could be performed in 95% of the cases and was amplified in 16%. Of the amplified cases 75 % were male and 25% female without significant enrichment for male or female. The median age of the patients at diagnosis was 67 yrs (range 46 - 82). Stage at presentation was: 16% I; 17.3% II; 26.7% IIIa, 40% IIIb/IV. 97,3% of the patients were former or active smokers with a median of 40 pack years. The median progression free survival of patients with stage IIIb/IV disease was 11 months (95% CI 8-14; n=14). The median overall survival was not yet reached after a median follow-up time of 14 months (95% CI 11 - 17; n=24). We further screened for co-existing genetic lesions such as mutations in EGFR, BRAF, KRAS, PIK3CA as well as translocations of ALK and amplifications of ERBB2. Two patients demonstrated co-occurring PIK3CA mutations and one a BRAFmutation. Conclusions: Screening for FGFR1 is feasible under routine clinical conditions. By implementation of a regional molecular screening network the ability to screen for FGFR1 amplification was successfully expanded to non-academic centers and private practices. FGFR1 amplifications in squamous cell cancer of the lung are frequent (16%) and associated with smoking history. Screening for FGFR1 might pave the way for the application of new FGFR1 directed targeted drugs in squamous cell lung cancer.

7591 Background: Since the introduction of targeted therapy into the treatment of advanced NSCLC molecular imaging tools gain in importance for assessment of pharmacodynamics, prognosis and predict...

e21019 Background: In 1980 an increased EGFR (epidermal growth factor receptor) expression was discovered in non-small cell lung cancer (NSCLC) patients coupled to poor survival prognosis. It was observed that sensitivity to gefitinib and erlotinib is correlated to activating mutations in the kinase domain of EGFR present in a subset of NSCLC patients whereas at least the mutation T790M leads to resistance to tyrosine kinase inhibitors. To analyse the tumour DNA mutation profile of 20 NSCLC lung biopsies in exons 18, 19, 20, and 21 we made use of pyrosequencing and compared this method with Sanger-sequencing and results of an external supplier. Methods: All analyses were performed on formalin-fixed paraffin-embedded lung biopsies from randomly selected patients suffering from NSCLC with previous EGFR-mutation analyses by an external supplier. Sanger-sequencing was performed by Eurofins MWG Operon (Munich, Germany) with primers published by Yunxia et al. (2010). Pyrosequencing was performed with the Qiagen...

e18092 Background: EGFR mutations predict response to erlotinib treatment in advanced NSCLC. However, identification of EGFR mutations is not always possible due to lack of adequate tissue. We ther...

e19054 Background: EGFR mutations predict response to erlotinib treatment in advanced NSCLC. However, also a subgroup of patients with wildtype EGFR benefits from erlotinib treatment. This subgroup could not yet be defined by molecular means. In this trial we set out to prospectively evaluate the accuracy of [18F]FDG-/[18F]FLT-PET analyses for early prediction of non-progression in chemo-naive patients with advanced NSCLC treated with erlotinib. Methods: Patients with NSCLC stage IIIB/IV without prior systemic treatment for NSCLC were eligible and treated for 6 weeks with erlotinib in this single centre diagnostic pilot trial. Primary endpoint was the accuracy of [18F]FDG/18F[FLT] PET after 1 week of treatment to predict non-progression as defined by RECIST criteria in CT scans after 6 weeks of treatment. Here we present the evaluation of 20 patients of this ongoing trial in accordance with the data monitoring board (EudraCT number 2005–005393–73; NCT00568841 ). Results: Twenty patients were recruited from 9/07 to 9/08. Seventeen patients were eligible for final analysis. The AUC for [18F]FDG PET at week 1 to predict non-progression was 0.857 ±0.105 (p=0.013) and 0.643±0.137 (p=0.32) for [18F]FLT PET. Using [18F]FDG PET specificity was 1 and sensitivity 0.71 for prediction of non- progression after six weeks (p=0.006 Fishers exact). In addition, [18F]FDG PET after 1 week of treatment clearly predicted tumor non- progression after 18 weeks of treatment with a predefined cut-off of -20% change in sSUVmax. (p=0.0004, Fisher´s exact). Finally, using this cut-off value [18F]FDG-PET after one week of treatment, predicted progression free survival (p=0.001, log rank test), with differences in median PFS of 45 days vs 320 days. Using univariable Cox regression, both [18F]FDG and [18F]FLT PET predicted PFS [hazard ratio 2.1 (p=0.006, Wald test) and 2.3 (p=0.011), respectively, per standard deviation]. Conclusions: Our observations indicate that early [18F]FDG but not [18F]FLT PET analysis predicts non-progression after 6 weeks of first-line erlotinib treatment in patients with advanced NSCLC. In addition, early [18F]FDG PET predicts non-progression after 18 weeks of treatment and progression free survival. [Table: see text]

3012 Background: IGN101 is a cancer vaccine acting via the epithelial cell adhesion molecule (EpCAM) expressed on epithelial cancers. It consists of 0.5 mg alum-adsorbed murine Mab 17–1A that bears...

1509 Background: The disastrous 2-year survival rate of only about 15% in lung cancer is mainly due to diagnosis of the disease in advanced stages. Early detection thus may be a promising strategy ...