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e21144 Background: Immune-checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape of lung cancer patients. However, its low treatment efficacy is still an issue and the current standard of care tissue PD-L1 presents high variability. Liquid biopsy is a promising tool in the discovery of biomarkers in body fluids. In particular, extracellular vesicles (EVs) can present PD-L1 in their membranes, playing a role in the inhibition of the anti-tumor immune response. Likewise, TGF-β is crucial in the immune response found in the circulation and into EVs. On the other hand, radiomics analysis of conventional imaging provides information about tumor heterogeneity and immune response. Hence, we aimed to evaluate the predictive role of circulating biomarkers in lung cancer patients undergoing ICIs and the additional value of radiomics data. Methods: This is a retrospective analysis of 30 advanced/metastatic non-small lung cancer patients treated with ICIs. Plasma samples were collected at baseline and at 8 weeks during treatment, matching the first response evaluation. Patients with complete, partial response, or stable disease were classified as responders and those with progressive disease as non-responders following RECIST v1.1. EVs were isolated from plasma by ultracentrifugation and PD-L1 expression was revealed by immunoblot. Circulating and EV levels of TGF-β were analyzed by ELISA. Additionally, 400 radiomics features from target and non-target lesions were analyzed to evaluate response in 24 patients according to RECIST v1.1 and irRECIST. Robustness of predictive models was validated by ridge penalty and leave-one-out cross-validation. Results: The analysis of the dynamics of EV PD-L1 during treatment identified increased levels in non-responders in comparison to responders ( p= 0.012), while tissue PD-L1 levels were not associated to the response ( p= 0.585). The predictive model for EV PD-L1 reported a high accuracy with an area under the curve (AUC) = 77%, 91.7% sensitivity, and 61.1% specificity. The combination with radiomics, improved the accuracy and reported an AUC = 83%, 82% sensitivity, and 77% specificity. Additionally, the analysis of the association of the circulating biomarkers with the outcome revealed that increasing dynamics of EV PD-L1 and high baseline EV TGF-β were associated with shorter progression-free survival and overall survival, outperforming the circulating levels of TGF-β. Conclusions: This pilot study demonstrated that EV PD-L1 could serve as better predictive factor than tissue PD-L1 for the stratification of lung cancer patients undergoing ICIs and that it could be complemented with radiomics. Moreover, EV levels of PD-L1 and TGF-β have potential for the stratification and prognosis of patients treated with ICIs and their novel combinations with TGF-β blockade.

9114 Background: Hypoxia has been associated with chemo-radioresistance secondary to Vascular Endothelial Growth Factor Receptor induced by Hypoxia Induced Factor (HIF). Nitroglycerin (NTG) can reduce HIF-1 in cell lines, and this may have anti-angiogenic, pro-apoptotic, and anti-efflux effects. Particularly, EGFR mutated (EGFRm) tumor cell lines have been shown to overexpress both VEGF and HIF. In this phase II study, we evaluated the effect of transdermal NTG on intracranial objective response rate (iORR), intracranial progression-free survival (ICPFS), and overall survival (OS) of NSCLC patients with BM. Methods: We performed an open-label, phase II clinical trial among ninety-six histologically confirmed NSCLC patients with BM. Patients were randomized 1:1 to receive NTG plus WBRT (30 Gy in 10 fractions) or WBRT alone. iORR and ICPFS were evaluated by MRI by two independent, blinded radiologists. Nitroglycerin was administered using a transdermal 36 mg patch, which released 10 mg in 24 hours with a rest interval of 12 hours from Monday-Friday throughout WBRT administration (10 days). Results: Fifty patients were allocated to the control group, while 46 were allocated to the experimental group (NTG); among these 26 (55.3%) had EGFRm in the control group and 21 (44.7%) had EGFRm in the NTG arm. In terms of the iORR, patients in the NTG group had a significantly higher response when compared to controls (56.6% vs. 43.5%; p = 0.024). Additionally, patients who received NTG in addition to WBRT had an independently prolonged ICPFS compared with those who received WBRT alone (27.7 vs. 9.6; HR: 0.470 [95%CI: 0.24-0.89]; p = 0.021). PFS was also positively impacted (HR: 0.519 [95%CI: 0.27-0.98]; p = 0.043). The benefit in terms of iORR and ICPFS (HR: 0.38 [95%CI: 0.16-0.91]; p = 0.030) was particularly important in the EGFRm patient subgroup. No differences were observed in OS. A significantly higher rate of vomiting presented in the NTG arm of the study ( p= 0.016). Conclusions: The concurrent administration of NTG and chemo-radiotherapy improves iORR and ICPFS among NSCLC patients with BM. The benefit is particularly significant in the EGFRm patient subgroup. Clinical trial information: NCT04338867.

TPS9083 Background: Despite several recent checkpoint inhibitor approvals extensive stage small cell lung cancer (SCLC) is associated with a poor prognosis and remains an area of high unmet need. RRx-001 is a first-in-class, minimally toxic small molecule immunotherapeutic that inhibits c-Myc, downregulates the antiphagocytic checkpoint, CD47, repolarizes tumor associated macrophages (TAM) from protumor M2 to antitumor M1 and resensitizes to previously active first line therapies. On the basis of favorable results from a Phase 2 trial called QUADRUPLE THREAT (NCT02489903) in combination with a platinum doublet in later line SCLC, a Phase 3 trial called REPLATINUM was started in 3rd line or beyond SCLC in Q4 2019. Enrollment is ongoing. Methods: This US-based, open-label, randomized, phase 3 study (NCT03777657) compares RRx-001 4mg + a platinum doublet (carboplatin or cisplatin + etoposide) versus a platinum doublet for pts with 3rd line or beyond SCLC that have previously received a checkpoint inhibitor. Approximately 120 pts from 25 centers will be randomized 1:1 to receive RRx-001 4 mg in combination with a platinum doublet vs. a platinum doublet. The platinum doublet will be administered on both arms for up to 4 cycles; on the RRx-001 arm only patients with stable disease or better are eligible to continue on RRx-001 4 mg + carboplatin AUC 2-4 maintenance therapy. If radiologic progression occurs on the control arm prior to the 4th cycle, patients are eligible to crossover to the RRx-001 treatment arm. PFS is the primary endpoint. Secondary endpoints include OS and ORR. Exploratory endpoints include c-Myc, CD-47 and PD-L1 on circulating tumor cells and SIRP-alpha expression on circulating monocytes. Clinical trial information: NCT03777657.

e21569 Background: Human papilloma virus (HPV) is associated with the development of several primary tumors. Recent studies have shown that HPV-positive tumors tend to be sensitive to immune checkpoint inhibitors (ICI), owing to the presence of xenobiotic genomes in cancer cells. The objective of this study was to explore this relationship in patients with lung adenocarcinoma. Methods: A retrospective cohort analysis in patients with advanced lung adenocarcinoma treated in a reference center in Bogota, Colombia was conducted. Demographic as well as treatment variables were collected between January 2018 and December 2019. Besides clinical outcomes, HPV infection status was determined by PCR amplification and reverse line hybridization directly on formalin-fixed paraffin-embedded tumor samples. Statistical analyses included stratified survival analysis based on HPV status and response. Results: A total of 133 patients were included. Male predominance (51.1%) with Karnofsky performance scores (KPS) greater than 80, and 19% of prior cigarette exposure (26 patients) was identified in the cohort. HPV positivity was identified in 25.6% of patients (33 cases, [95%CI 17.5-32.2%]), in addition to 29.8% EGFR mutation positivity (29 cases [[95%CI 14.8-28.8%]), 6% ALK positivity (8 cases [95%CI 1.9-10]) and positive PD-L1 expression in 49 samples (36.8% [95%CI 28.6-45%]). In immune checkpoint inhibitor (ICI) exposed patients, HPV+ patients had significantly higher PD-L1 expression compared with HPV- individuals (p < 0.001). In terms of overall survival, ICI treated patients achieved an OS of 27.1 months (95%CI 22.1-NA) and a PFS of 19.4 months (95%CI 18-24.5 months). HPV infection status was associated with prolonged OS (median OS not reached, [95%CI 27.7 months – no reached], p = 0.0089) and better response to ICI (p < 0.001). Conclusions: HPV infection is prevalent in patients with lung adenocarcinoma and is associated with better response to ICIs as well as better survival outcomes. Its identification could serve as a prognostic marker, especially in female non-smoker patients.

e21566 Background: Several histopathological markers have been associated with immune system activity and its relationship with clinical outcomes in lung cancer. Determination of tumor infiltrating lymphocytes as well as specific subpopulations could reveal cytotoxic potential. Additionally, changes in stromal composition and fibrosis could also reflect potential cellular interactions with the tumor lesions. In this study we validate these two findings as potential prognostic factors. Methods: A retrospective cohort analysis of patients with advanced lung adenocarcinoma treated in a reference center in Bogota, Colombia was conducted. Demographic as well as treatment variables were collected between January 2018 and December 2019. In addition to clinical outcomes, the percentage of stromal fibrosis and immunoscore were estimated for all biopsy samples by a trained oncological pathologist. Results: A total of 133 patients were included. Male predominance (51.1%) with Karnofsky performance scores (KPS) greater than 80 and 19% of prior cigarette exposure (26 patients) was identified in the cohort. Median overall survival of the cohort was 27.1 months (95%CI 22.1-NA) and progression free survival of 19.4 months (95%CI 18-24.5 months). Percentage of fibrous stroma and immunoscore were associated with a benefit in both OS and PFS. For patients who presented with a low stromal fibrosis, defined as harboring less than 10%, OS reached a median of 25.1 months (95%CI 21.5- 40.5 months) compared to 38.7 months for patients with high fibrosis (95%CI 27.7 months – NA), (p = 0.02). In terms of immunoscore, values under 40% were associated with a longer median OS (38.7 months, [95%CI 31.3- 58.6 months] vs 22.1 months [95%CI19.8- 42.3 months], p < 0.001). Immunoscore and stromal fibrosis were not codependent variables (p < 0.001), suggesting that these markers offer independent prognostic value with regards to OS. Conclusions: Stromal fibrosis and immunoscore serve as prognostic factors that could be easily interpreted and evaluated in order to offer prognostic classification of patients with metastatic adenocarcinoma of the lung.

3605 Background: NTRK gene fusions lead to transcription of chimeric TRK proteins with overexpressed kinase function. Entrectinib is a potent inhibitor of TRKA/B/C. In phase 1/2 studies (ALKA, STARTRK-1, STARTRK-2; EudraCT 2012-000148-88; NCT02097810; NCT02568267), entrectinib was effective in pts with NTRK-fp solid tumors. We present updated data in a larger population with longer follow-up. Methods: In this integrated analysis of adult pts from 3 phase 1/2 trials (data cut-off 31 Oct 2018), tumors were assessed by blinded independent central review (BICR) with RECIST v1.1 (end of cycle 1; then every 8 wks). Primary endpoints were overall response rate (ORR) and duration of response (DOR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), efficacy in pts with/without baseline CNS disease, and safety. Results: There were 74 evaluable pts with advanced/metastatic NTRK-fp solid tumors (Table). Median duration of survival follow-up in all pts was 14.2 mo (range 0.1–29.7). BICR ORR was 63.5% (95% CI 51.5–74.4), with 5 complete responses (6.8%). Median BICR DOR was 12.9 mo (95% CI 9.3–NE); median BICR PFS was 11.2 mo (95% CI 8.0–15.7); median OS was 23.9 mo (16.0–NE). In pts with no baseline CNS disease (investigator-assessed; n=55), BICR ORR was 65.5% (95% CI 51.4–77.8) and median BICR DOR in responders was 12.9 mo (95% CI 9.3–NE). In pts with baseline CNS disease (investigator-assessed; n=19), BICR ORR was 57.9% (95% CI 33.5–79.8) and median BICR DOR in responders was 6.0 mo (95% CI 4.2–NE). Safety was in line with that previously reported; the most common ≥grade 3 treatment-related AEs were weight gain (8, 7.1%), anemia (8, 7.1%), and fatigue (7, 6.2%). Conclusions: In this updated analysis, including more pts and longer follow-up, entrectinib continued to demonstrate clinically meaningful responses in pts with NTRK-fp solid tumors, with and without baseline CNS disease. Clinical trial information: NCT02097810, NCT02568267 . [Table: see text]

TPS9078 Background: While the role of surgery in limited-stage (stage I-III) malignant pleural mesothelioma (MPM) is controversial, many centers have adopted an aggressive tri-modality approach incorporating (neo)adjuvant chemotherapy, surgical resection and radiotherapy. Despite this, most patients relapse and die from their disease. Immune checkpoint blockade (ICB) has shown promise in advanced MPM, but the mechanisms of response and resistance remain elusive. Improving the mechanistic understanding of ICB in MPM while concurrently optimizing the treatment strategy for limited-stage MPM are two urgent unmet needs. This multicenter multi-arm phase I/II study seeks to evaluate the safety and feasibility of neoadjuvant ICB in resectable MPM, incorporating novel genomic and immunologic analyses to deliver mechanistic insight into the biology of ICB in MPM. Methods: Patients with surgically resectable stage I-III treatment-naïve epithelioid or biphasic MPM receive neoadjuvant treatment with nivolumab every 2 weeks for 3 doses with or without 1 dose of ipilimumab (arm A: nivolumab monotherapy; arm B: nivolumab + ipilimumab). After macroscopic complete resection, patients receive optional investigator-choice adjuvant chemotherapy +/- radiation. Following this, patients will receive up to 1 year of adjuvant nivolumab. Feasibility and safety are co-primary endpoints of this study with feasibility defined by a delay in surgery of ≤24 days from the preplanned surgical date and safety defined by adverse events according to CTCAE v5.0. Bayesian-designed stopping rules have been implemented for feasibility and safety. Secondary endpoints include assessment of pathologic response and radiographic response using RECIST 1.1 for MPM. Correlative analyses will be performed on tissue specimens obtained pre- and post-ICB, as well as blood obtained pre, during, and post-ICB. Key correlates include multiplex immunofluorescence and longitudinal ctDNA assessment. Whole exome sequencing, T-cell receptor sequencing, and the MANAFEST functional neoantigen assay will be utilized to identify neoantigen-specific T-cell clonotypes and track these clonotypes temporally (during/post ICB) and spatially (across immune compartments). Single-cell RNA sequencing will be used to characterize the functionality of expanded T-cell clonotypes. Accrual to arm B will commence following complete accrual to arm A with a planned total enrollment of 30 patients. This study is open with 1 patient enrolled at the time of submission. Clinical trial information: NCT03918252.

TPS3159 Background: A major paradigm in cancer immunotherapy is to use checkpoint inhibitors to break regulatory mechanisms that guard the host against autoimmune diseases. CTLA-4-targeting immunotherapy was the first example to establish this paradigm. However, the clinically tested anti-CTLA-4 antibodies exhibit suboptimal efficacy but high toxicity. Our recent studies have demonstrated that immunotherapy-related adverse events (irAE) and the cancer immunotherapeutic effect (CITE) represent distinct and therapeutically separable activities of anti-CTLA-4 antibodies. The irAEs are attributable to inactivation of the CTLA-4 checkpoint, while the CITE is effective through selective depletion of regulatory T cells (Treg) in the tumor microenvironment. We hypothesize that a safer and more effective CTLA-4-targeting immunotherapy should preserve the CTLA-4 checkpoint while enhancing the efficacy and selectivity of Treg-depletion in tumor microenvironment. In preparation to test this ground-breaking hypothesis clinically, we have generated a next generation of anti-CTLA-4 antibody that preserves the CTLA-4 immune checkpoint by avoiding lysosomal degradation of CTLA-4. The new antibody, ONC-392, has dramatically lower irAEs in a humanized mouse model and significantly more potent activity in depleting tumor-infiltrating Tregs, resulting in more effective CITE. Methods: This is an open label Phase IA/IB clinical study to test the safety, pharmacokinetics (PK), and efficacy of ONC-392 as a single agent and in combination with Pembrolizumab in advanced solid tumors and non-small cell lung cancer patients. The study consists of two linked parts: Part A is a dose-finding rapid titration study, with ONC-392 as a single agent in patients with advanced disease of various histology. The aim of this trial is to define the recommended Phase II dose for ONC-392 monotherapy (RP2D-M), Part B is a Phase IA/IB trial of ONC-392 in combination with a standard dose of 200 mg Pembrolizumab in patients with NSCLC. The trial consists of a dose-finding, dose escalation or de-escalation, Phase IA component aimed at defining the recommended phase II dose for ONC-392 in combination with a standard dose of Pembrolizumab (RP2D-C), then progressing into two parallel, single arm, Phase IB expansion cohorts to test for safety and initial efficacy in two groups of patients with NSCLC: Stage IV NSCLC anti-PD(L)1 immunotherapy naïve with PD-L1-positive (PD-L1 TPS ≥ 1%); Stage IV NSCLC refractory/resistant to anti-PD(L)1 immunotherapy. Clinical trial information: NCT04140526 .

e24078Background: Cytidine deaminase (CDA) plays a crucial role in gemcitabine degradation. In previous mono-/multi-center retrospective studies CDA activity emerged as the strongest biomarker of a...

TPS2615Background: Next generation sequencing of solid tumors will increasingly reveal mutations in cancer genes, including EGFR, HER2 and HER3 mutations. Afatinib is a small molecule, which select...

e24288Background: Abnormal changes in the metabolism are cancer hallmarks and can be used as therapeutic targets. Our study aim was to identify enriched metabolic pathways in patients (pts) with sq...

e24318Background: Evaluation of healthy lung tissues sections from patients with lung cancer as comparator for genomic studies could produce an unwanted bias because the healthy tissue is also expo...

e18511Background: Molecular Tumor Boards (MTBs) for patient selection and assessment of treatment options were created for adequate precision medicine delivering. We evaluated the implementation of...

1014Background: SYD985, (vic-)trastuzumab duocarmazine, is a HER2-targeting antibody-drug conjugate with a cleavable linker-duocarmycin payload that causes irreversible alkylation of the DNA in tum...

521 Background: Despite recent improvements in chemotherapy for pancreatic cancer that have demonstrated improvements in survival, response rates remain at less than 50%. Distinct molecular subgroups of pancreatic cancer that harbor specific actionable molecular alterations have recently been identified. These include gene fusions of the receptor tyrosine kinases NTRK and ROS1. Entrectinib is a CNS-active, potent, and selective TRK and ROS1 inhibitor that has shown substantial clinical activity in patients with locally advanced or metastatic solid tumors that have NTRK or ROS1 fusions (Drilon A, et al. Cancer Discov. 2017;7[4]:400-409). Methods: We examined 3 cases of pancreatic cancer where an actionable gene rearrangement was identified: 2 with a TPR-NTRK gene fusion, and 1 with an SCL4-ROS1 gene fusion. All 3 patients were treated with entrectinib 600 mg daily in a phase 2 trial (NCT02568267). Results: Entrectinib was well tolerated with mostly grade 1-2 adverse events consisting primarily of arthralgias, myalgias, and fatigue. All 3 patients showed evidence of clinical improvement, with normalization of the tumor biomarker CA19-9 and confirmed partial responses as per RECIST v1.1 in the 2 patients with a TPR-NTRK fusion, 1 of which was associated with a significant decrease in metabolic activity as assessed by PET/CT scan. The patient with the SCL4-ROS1 fusion had stable disease for at least 6 months. All 3 patients had an improvement to, or maintenance of, a high quality of life while on study. At the time of data cutoff, 1 of the patients with a TPR-NTRK fusion remained on treatment > 1 year. Conclusions: Entrectinib treatment was associated with response and prolonged disease control in these 3 patients with NTRK or ROS1 fusion-positive pancreatic cancer. NTRK and ROS1 gene fusions are rare in pancreatic cancer. The true incidence is unknown, as routine testing for gene fusions in pancreatic cancer is not yet standard practice. Given the benefit seen here with entrectinib and the clinical need for improved therapeutics, there may be value in broader and earlier molecular testing of patients with pancreatic cancer for these actionable fusions. Clinical trial information: NCT02568267.

e18208 Background: Health Information Technology (HIT) is increasingly integrated in clinical cancer care. Simultaneous routine assessment of patient reported outcomes (PROs) reliably improve symptom management, patient-provider communication and ultimately survival. Methods: his pilot study is a single center experience with the development and validation of an I-PRO tool (AMOCT). After obtaining informed consent, outpatients, using oral anticancer treatment, recorded their medication intake and 17 PRO measures (PROM) using this I-PRO tool. The device allowed real time data collection via a central platform. The registered data were processed by an algorithm, which stratifies the data into different grades according to international standards of care (CTCAE v4.0). In response to registration of data, patients received either automated symptom management suggestions or were referred to their caregivers. Patient clinical and demographic information is collected from medical records and analyzed using descriptive statistics. Results: 63 Patients were included, 51% male, mean age 61.5 (range 28-83). 41% Of patients used capecitabine, 24% regorafenib, 16% TAS 102, 5% pazopanib and 5% sunitinib. Of the 1873 PROM-scores, 308 scores needed nurses’ attention, ultimately leading to dose reductions in 7 patients (12%). Most often due to weight loss, skin toxicity and asthenia. 41 Patients stopped registration: 51% because treatment ended, 27 % died, 10% dropped out, 5% progressed, 5% were lost to follow up and 2% never started. This tool was well adopted and demonstrated treatment compliance in > 85% patients. Conclusions: This study confirms the feasibility of the program, in an outpatient setting. This I-PRO tool provides a means to register compliance and toxicity of treatment. The compliance to the I-PRO tool will be confirmed, with further development of this program in a multicenter, randomized design. Evaluation of quality of life, PROM’s and further exploration of the relationship between optimal pharmacovigilance and improvement of patient’s outcome will ensue.

e20553 Background: NSCLC therapeutic paradigm has changed with immune checkpoint blockers. Biomarkers predicting clinical benefit are still lacking. As previously shown in melanoma, changes in absolute lymphocytes and neutrophils count (ALC and ANC) during IT (PD-1/PD-L1 inhibitors) may be related to response in NSCLC (Nakamuta et al, Oncotarget 2016). TTF1 expression has been associated with PD-L1 expression (Vieira et al, Lung Cancer 2016). We aimed to investigate TTF1 expression and changes in ALC and ANC after 2 cycles and their potential association with clinical outcomes to IT. Methods: We retrospectively analyzed 26 consecutive patients with stage IV NSCLC treated with IT at Clínica Universidad de Navarra (Spain) during 2016. Radiological response was evaluated according to RECIST v1.1. The potential correlation between ALC and ANC changes during the first two cycles and response to treatment [disease control rate (DCR) vs progression] was evaluated using Student’s T-test. Fisher’s exact test was used to study the association between changes in ALC ( < 1,000 vs > 1,000) and ANC ( < 4,000 vs > 4,000) after 2 cycles and response to IT. TTF-1 expression was correlated with treatment response. Overall survival (OS) was assessed with Kaplan-Meier analysis and Log-rank test according to ALC and ANC. Results: An ALC increase after 2 cycles was significantly associated with DCR compared to progression (192 vs -155; p = 0.043). ALC > 1,000 after 2 cycles was more frequent among patients experiencing DCR compared to progression (87% vs 50%; p = 0.07). ALC > 1,000 after 2 cycles was more frequently observed among patients with TTF1+ tumors (93% vs 55%; p = 0.03). Patients with ANC < 4,000 showed a longer median OS (NR vs 19.25 months; p = 0.03). TTF1 expression in adenocarcinoma (n = 18) was associated with response to IT (83% vs 16%, p = 0.01). Conclusions: Despite this retrospective small series’ limitations, our results show that ALC and ANC changes during IT and TTF1 expression may act as early predictors of clinical benefit in stage IV NSCLC patients treated with PD1/PD-L1 blockers. Our results warrant further investigation in larger prospective series.

e20569 Background: About 5% of NSCLCs present alterations in the ALK gene. Among them the most common is EML4-ALK translocation. The gold standard detection method to treat the patient with ALKi is the tissue, thus, it is mandatory to develop new techniques that allow to detect ALK alterations in liquid biopsy. The purpose of this study is, analyze the feasibility to detect ALK alterations in exosomes (Exo-ALK) derived from NSCLC patients. Methods: We recruit 18 NSCLC patients including EML4-ALK and wild-type patients stage- and time-independent. ALK-positive status is identified by IHQ. The isolation of RNA with the exoRNeasy Kit Serum/Plasma (Qiagen) in UZA and the retrotranscription with ProtoScript II First Strand cDNA Synthesis kit. The ALK alteration present in the exosomes is determined by NGS and bio-informatic analysis in OncoDNA. Samples were provided by the Biobank of the University of Navarra, the UZA Biobank and the University of Naples Federico II. Samples and data were processed following the processes approved by the local Ethical and Scientific Committees. Results: Among analyzed patients, 15 patients were EML4-ALK tissue positive, and 3 were EML4-ALK tissue negative. With our analysis, 9 patients were positive, 7 negative and 2 sample were degraded at the time of analysis. Comparing the results, the 9 positive patients in the exosomes were also positive in the tissue. Moreover, the 2 negative patients were also negative for the translocation in the tissue. However, we were unable to detect 4 positive EML4-ALK patients in the exosomes. Nonetheless, these data show a sensitivity of 69% and a specificity of 100%. No correlation was found comparing treatment-naïve and pretreated patients. Conclusions: Exosomes are raising as a very promising tool to determine the tumor profile due to their stability and their cargo. With further study and a larger number of patients, we demonstrate that exosomes isolation and analysis will be feasible tool, and thus we will reduce the tumor biopsy risks and costs in the clinical practice. Our preliminary results show a good specificity for a proof of concept analysis. These results will be cross-validated and amplified with more patients in the following months.

e18113 Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. It is well known that there are differences in the outcome between genders; however the effects of the sex in the prognosis have not been previously properly defined. Our aim was to evaluate in a meta-analysis, differences in healthcare outcomes between women and men with NSCLC in terms of overall survival (OS) and progression-free survival (PFS). Methods: We searched for references of published studies of hospitalary databases indexed in PubMed/Medline. We retrieved 67 references (from 1989 to 2016), of which eleven references were eligible for data extraction. In total, 11 references were evaluable for OS. Meta-analysis for Hazard Ratios (HR) obtained from univariate and multivariate analysis were analyzed in different groups. The meta-analysis was done in the software Review Manager 5.3. Results: In total, 7 studies had information for OS univariate analysis, 7 studies for OS multivariate analysis, only, one for PFS univariate analysis and one for PFS multivariate analysis. The meta-analysis for OS univariate analysis resulted in a HR = 0.75 (P < 0.00001; 95% CI: 0.71 to 0.79) for women compared to men, although there was a high statistical heterogeneity between cohorts (P < 0.0001). In the meta-analysis for OS multivariate analysis was estimated a HR = 0.75 (P < 0.00001; 95% CI: 0.73 to 0.78), with statistical heterogeneity between cohorts (P = 0.0005). Conclusions: Our study quantified a 25%-risk reduction of death for women with NSCLC compare with male men patients with the same diagnosis.

e20043 Background: Targeted therapies caused a revolution in treatment of non-small cell lung cancer (NSCLC). Response to Epidermal Growth Factor Receptor such as erlotinib, can be predicted by the presence of sensitizing mutations in EGFR. In case of cMET, amplification or exon 14 skipping serve as biomarkers for response to cMET-TKIs, crizotinib. Methods: In this study, we investigated the combination of erlotinib and crizotinib on several squamous NSCLC cell lines wild-type for EGFR and cMET. Growth inhibition was determined using the sulforhodamine B-assay. Combination indexes (CI) were calculated based on the method of Chou and Talalay. A CI below 0.8 was considered synergistic, between 0.8 and 1.2 was considered additive and above 1.2 was considered antagonistic. The influence of treatment on the cell cycle, cell migration, 3D cell cultures and phosphorylation was studied. Results: The H1703 cell line gave an antagonistic (CI = 1.20±0.15), the Calu1 (CI = 0.81±0.04), H520 (CI = 0.87±0.06) and SKMES1 (CI = 0.81±0.02) were additive and LUDLU (CI = 0.39±0.07) was synergistic. A G1 phase arrest occurred after treatment with erlotinib (38 to 76%), whereas crizotinib caused a G2/M phase arrest (13 to 64%). In the combination, the effect of crizotinib was dominant (13 to 52%). A decrease in p-ERK1/2 (Thr202/204), p-PRAS40 (Thr246) and p-GSK3 β (Ser9) was observed. Phospho-PRAS40 showed a decrease after treatment with erlotinib or crizotinib, whereas combination treatment almost abolished p-PRAS40. In the SKMES1 cell line, p-PRAS40 only decreased after the combination, whereas H1703 cells showed no change in p-PRAS40 levels. Phospho-PRAS40 activity is strongly linked to PI3K/Akt signaling. Her3 is able to heterodimerize both with EGFR and cMET, thus activating downstream PI3K/Akt signaling. No expression of Her3 in the antagonistic cell line was detected. In the LUDLU, levels of p-Her3 were not detectable after erlotinib treatment and in the combination, whereas in the SKMES1 levels of p-Her3 slightly decreased only after combination treatment. Conclusions: To conclude, the simultaneous inhibition of both EGFR and cMET leads to a strong inhibition of PI3K/Akt signaling, leading to synergy in the LUDLU wild-type squamous NSCLC cells.

e23035Background: NSCLC patients harboring EGFR mutations are able to receive approved tyrosine kinase inhibitors (TKIs) but to better assess the treatment responses new tools are needed. Liquid bi...

7556Background: Background: CD70 is a cell surface marker transiently expressed on activated B, T and dendritic cells. The interaction via its receptor CD27 results in survival, proliferation and l...

e14016Background: ARGX-111 is a therapeutic antibody candidate combining three independent MoA: i. blockade of HGF-dependent and -independent MET activity, ii. enhanced ADCC and iii. increased tissue penetration through enhanced FcRn binding. A Phase-I study (NCT02055066) in patients with c-MET-amplified tumors is ongoing. A new hypothesis for depletion of MET-positive MDSCs in the tumor microenvironment is also investigated. Methods: c-MET amplification detected using FISH on tumor biopsies is a prescreening requisite for patient selection in the expansion phase. MDSCs were enumerated by FACS using blood and ascites from patients or tumor and spleen tissue from a mouse CT26 syngeneic tumor model. Results: ARGX-111 dose escalation indicated a favorable safety profile and fixed a 3 mg/kg bi-weekly dose for the safety expansion in c-MET-amplified patients. Efficacy signals were seen in the c-MET-amplified setting [J Clin Oncol 33, 2015 (suppl; abstr 2580)]. FISH screening identified 4% of c-MET-amplified bi...

3565Background: Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of li...

e23166Background: It has become evident that both pathological and molecular genetic disease stratification has major impact on therapeutic decisions and outcomes. However, combination of such canc...

TPS3632 Background: RAS is mutated (RASMT) in ~55% of mCRC, and phase III studies have shown that patients harbouring RAS mutations do not benefit from anti-EGFR MoAbs. In addition, ~50% of RAS Wil...

e13563 Background: Chronic myeloid leukemia is a myeloproliferative disorder that comes from a hematopoietic stem cell or a multipotent progenitor. Exosomes are biological nanovescicles (40-100 nm)...

e22155 Background: Clinical phase I trials are no longer aimed to study only pharmokinetics/pharmacodynamics or toxicity, but also investigating possible tumor responses, especially if patients (pt...

e19014 Background: In NS-NSCLC CPB achieved median OS > 1 y and supported use of B. A broad range of predictive/prognostic markers explored for B use. In VEGF pathway ligands and receptors play an ...

11028 Background: REV3, the catalytic subunit of the TLS polymerase ξ, can continue replication past DNA adducts. Depletion of REV3 sensitizes A549 lung cancer cells to cisplatin. REV3 expression is part of a gene signature that predicted pemetrexed sensitivity in 17 NSCLC cell lines. Homologous recombination and TLS pathways have non-redundant functions in response to cisplatin. We hypothesized that low REV3 mRNA expression – alone or in combination with low expression levels of genes involved in homologous recombination – could correlate with better outcome to cisplatin/pemetrexed in NSCLC. Methods: REV3, BRCA1, RAP80, TS and AEG1 mRNA was examined by quantitative RT-PCR and categorized by terciles. Expression of each gene was correlated with outcome in 47 cisplatin/pemetrexed-treated NSCLC p. Results: 63.8% male; 47% smokers; 80.9% ECOG PS 1; 80.8% adenocarcinoma. Overall response rate was 51%, with no differences according to expression levels of any of the genes. Progression-free survival (PFS) for p with low, intermediate and high BRCA1 levels was 13.4, 5.5 and 3.9 months (m), respectively (P=0.005). Similar differences in PFS were observed according to TS (P=0.003) and AEG1 (P

e12012 Background: There is very little information about the menstrual status in women presenting with lung cancer. In other tumors, the menstrual status constitutes an independent prognostic factor. We proposed to investigate whether this status has any influence in clinical aspects, diagnosis or survival. Methods: WORLD07 is a Spanish prospective, multicenter, epidemiologic female-specific lung cancer database sponsored by ICAPEM, a professional association committed to WLC research. Results: Between October/2007 and October/2011, 1371 p newly diagnosed WLC were included in an e-database from 32 Spanish centers. Patient (p) characteristics were: median age 71.1 years (y)(range 22-91); median age of menarche 13y.; motherhood 91.2% (median 2.3 children, median age at first child 26.4y); oral contraceptive use 11.9%; postmenopausal 86% (median age of menopause 49y. No statistically significant differences were found with respect to menstrual status, clinical characteristics, histological type, nor in the TNM at diagnosis. Median overall survival in pre-menopause (preM) was 24.2 months (m) and 27.5 m in post-menopause (postM). Overall 1 year survival in both groups was similar, 70% IC95% (61.5-79.1%) in preM vs 72.4% IC 95% (69.15-75.7%) in postM, and at 2 years, was 50% in both. Conclusions: According to our e-database, the menstrual status does not have any significant influence in the presentation, histologic type or survival in women with lung cancer.

7058 Background: Tregs play a critical role in immune tolerance to tumor cells and have been related to prognosis. The aim of this study was to determine the expression of Tregs makers genes by RT-PCR and to correlate them with clinico-pathological and prognostic variables in NSCLC. Methods: RNA was isolated from frozen lung specimens (tumor and normal lung) from resectable NSCLC patients (n=175). RT-PCR was performed to analyze the expression of: CD4, CD8A, CTLA-4, FoxP3, IL-10, CD25, CD127 and TGFβ-1. Relative expression was normalized by an endogenous gene (GUSB) using the Pfaffl formulae. Statistical analyses were considered significant at p

10594 Background: Angiogenesis is a key mechanism in tumor growth and dissemination mainly regulated by VEGF family members. We analyze the expression of 11 angiogenic genes in a cohort of resectable NSCLC patients and correlate them with clinico-pathological variables and prognosis. Methods: RNA was obtained from tumor and normal lung specimens from 175 NSCLC patients. RT-PCR was performed to assess the expression of HIF1-A, PIGF, VEGFA, VEGFB, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, NRP1 and NRP2. Relative expression was normalized by an endogenous gene (GUS) using the Pfaffl formulae. Differences were considered statistically significant at p

4587 Background: The effect of pemetrexed in MUC is not well characterized. Vinflunine is the standar second-line in MUC with adjusted benefits and no more drugs have been aproved. SOGUG reports a systematic review of MUC patient series with high activity of P in monotherapy. Methods: Patients with locally advanced urothelial carcinoma and/or MUC whom received P 500 mg/m(2) every 21 days with folic acid and vitamin B12 supplementation, were elected. These patients received P in second, third or fourth-line of chemotherapy. Results: 44 patients have been reported (39males), median age 62 [41-82]. Of all 44 patients; 21, 22, and 1 patients received P as second-line, third and fourth-line respectively. A median of 4 courses were administered [1-12] and disease control (SD+PR+CR) was achieved in 19 patients for an overall control rate of 43.2%. Four groups with significant differences in PFS (p=.033) were established (1.bone-metastasis, 2.visceral-metastasis, 3. nodal-visceral-metastasis and 4.nodal-metastasis). OS was significant between 2nd and 4th group (p=.036) . Mean PFS and OS were 125days [17-606] and 219days [17-1168] respectively for all 44 patients. Mean PFS and OS of 8 patients with bone metastasis were 75 days and 134 days. Mean PFS and OS of 10 patients with visceral metastasis were 65 days and 144 days. Mean PFS and OS of 8 patiens with nodal+visceral metastasis were 154 and 228 days. Mean PFS and OS of 18 patients with nodal metastasis were 166 days and 299 days. Conclusions: Our longer and multicenter follow-up shows that single agent P in monotherapy as second, third and fourth line in MUC is associated with high activity and long-time survival specially in metastatic nodal MUC. These results suggest that P as monotherapy requires to be further studied, more patients are being collected.

e15120 Background: Patients with MUC relapsing after standard chemotherapy perioperative or after localy advanced or metastatic disease, have no good treatments. We report our series with high acti...

20629 Background: Fatigue is one of the cancer-related symptoms that has the greatest impact on patients’ lives. This survey was designed to better understand the functional and psychological impact of fatigue and to determine, according to the patient’s perception, the load of fatigue relative to other symptoms. Methods: A cross-sectional, self-administered survey was conducted from August-October 2007. Patients were ≥18 years old, with a diagnosis of cancer, and had received their last therapy session 2–12 months ago. Demographic and tumor information were collected. The survey included 6 questions about the emotional and social impact of fatigue and the patient’s perception of the oncologist’s response to reports of fatigue. Fatigue impact on emotional well-being was measured by a visual analogue scale (0–100). Questions about functional and social impact were rated on a 5-point Likert scale. Descriptive statistics were used to summarize demographic variables and responses. Results: The survey was comp...

14544 Background: Based on the results obtained with Capecitabine (XEL), Oxaliplatin (OX), and CPT-11 (IRI), we proposed this exploratory study to asses the efficacy of XELIRI and XELOX, for advanced colorectal cancer, after a first line treatment with 5 FU plus OX (FOLFOX) or IRI (FOLFIRI). Methods: P aged = 18 with histological diagnosis of metastatic colorectal adenocarcinoma, were assigned to XELOX arm (XEL, 1000 mg/m2 BID during 14 d; OX, 130 mg/m2 d1; q3w) or XELIRI arm (XEL 1000 mg/m2 BID during 14 d; IRI 240 mg/m2 d1; q3w), depending on previous treatment (FOLFIRI or FOLFOX, respectively). Although sample size was calculated for 115 p, recruitment was premature closed due to the low inclusion rate related with cetuximab + IRI approval for second line treatment. Results: Forty three p (25 p, XELOX; 18 p, XELIRI) were enrolled: median age 63.2 years; M/F, 40.5%/59.5%; ECOG PS 0–1, 79.1%. All p have been previously treated for metastatic disease and 65.1% had stage IV. Main sites of metastatic disease were liver (71.8%), lymph nodes (7.7%), pelvis (7.7 %) and lung (5.1%). XELOX/XELIRI treatment data: total number of administered cycles was 94/85 and median relative dose intensity 100%(XEL)/99%(OX) and 96%(XEL)/94%(IRI); disease control rate (PR+SD) was 28%/33.3%, median TTP 3.4/4.1 months, median OS 10.3/11.2 months and 1-year survival, 39.1%/44.3%, respectively. Twenty p (46.5%) received further antitumoral treatment. Most frequent G3–4 toxicities per p are detailed in table 1 . Conclusions: Capecitabine based combinations show an excellent toxicity profile and good efficacy results, in terms of disease control and survival rates, for advanced colorectal cancer patients previously treated with 5-FU schedules. [Table: see text] No significant financial relationships to disclose.