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Gastric cancer is the fifth most common neoplasm worldwide with high rates of mortality. Afatinib, a low molecular, irreversible potent inhibitor of ErbB trans-membrane receptor family, has shown promising results according to preclinical and phase I clinical trial data when combined with chemotherapy. We aimed at evaluating the safety and efficacy of the combination of cisplatin, 5FU with afatinib in molecularly unselected patients with advanced gastric cancer.Patients with locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma received first line combination therapy of cisplatin, 5FU and afatinib every 21 days, followed by afatinib maintenance monotherapy. The primary endpoint was the Objective Response Rate (ORR); secondary endpoints included Overall Survival (OS), Progression Free Survival (PFS) and the safety profile. Unplanned exploratory analysis of HER2 and tumor mutational profile was performed.Among 55 patients (ITT population) enrolled, 19 (34.5%) achieved an objective tumor response; stable disease was observed in 16 patients (29.1%) and progressive disease in 10 patients (18.2%). The ORR in the per protocol population (PP) was 42.9%. Within a median follow-up of 56 months, the median PFS and OS in the ITT population was 5.0 and 8.7 months, respectively. Seven of the 47 HER2 informative cases carried HER2 positive tumors whileThe combination of cisplatin/5FU with afatinib did not surpass the benchmarks of efficacy of the contemporary therapeutic regimens that are being applied for the treatment of patients with advanced gastric cancer. However, the observed efficacy and the improved safety profile support that our administration schedule may be further investigated to overcome toxicity problems when integrating afatinib to cytotoxic chemotherapy.NCT01743365.

Bladder cancer (BC) is a heterogeneous malignancy with dismal outcome.Mutations in genes, altered or linked to platinum sensitivity in BC, were examined in 66 patients' tumors along with tumor infiltrating lymphocytes (TILs) density and MMR, PD-L1 and CD8 protein expression, as well as basal and luminal subtypes, defined by protein expression of markers, including CK5/6 and GATA3 or CK20, respectively.41 tumors harbored mutations, mainly in TP53 (38%), ARID1A (17%) and the DNA damage response and repair (DDR) genes ERCC2 (17%) and BRCA2 (15%). Mutations in other DDR relevant genes were also present. Age showed unfavorable prognosis for overall survival (HR=1.07, P = 0.026); no benefit was seen for patients with TP53, ARID1A, ERCC2 or BRCA2 mutations or mutations in 1 or more DDR genes. PD-L1 status positively correlated with stromal (rho=0.46, P0.001) and intratumoral (rho=0.53, P0.001) CD8 expression or TILs (rho=0.29, P = 0.018); none associated with overall survival (OS). A statistically significant difference was observed between PD-L1 status and immunohistochemistry (IHC)‑based subtypes, with tumors classified as luminal (GATA3+ and/or CK20+ and CK5/6-) showing lower PD-L1 expression relative to basal (CK5/6+ and GATA3- and/or CK20-) (median value 0 vs. 2.5, P = 0.029). Concerning OS, no statistically significant difference was seen among patients with basal or luminal tumors.No association was seen herein between DDR mutations, TILs, PD-L1, CD8 expression or IHC-based subtypes and patient survival; these observations warrant validation within a larger cohort.

The efficacy of nab-paclitaxel in patients with metastatic breast cancer (MBC) has been demonstrated in randomized clinical trials. However, real-world evidence on effectiveness remains limited. The primary objective of this multicenter prospective study was to assess the overall response rate (ORR) of patients with MBC treated with nab-paclitaxel. Secondary objectives included progression-free survival (PFS), overall survival (OS) and quality of life, assessed with the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument. Eligible patients (N = 150; 36% with de novo MBC presentation) with a median age of 64.5 years were enrolled (86% were ER+, 33.3% (50/150) were ≥ 70 years of age and 53% were treated in the third or later line of treatment). A median of 6 cycles were administered but 26% of patients required dose reduction due to toxicity. The ORR was 26.7% [95% confidence interval (CI) 19.6–33.7], the median PFS was 6.2 months (95% CI 5.2–7.3), and the median OS 21.1 months (95% CI 17.2-not estimable). There was no statistical significant difference in the median PFS of patients

Background The mechanism of action of bevacizumab and erlotinib is quite different in the treatment of advanced non-small cell lung cancer (NSCLC). This study sought to compare the two targeted therapies in terms of sequential tumor response metrics. Patients and methods Parameters of radiological tumor response evaluation were assessed at baseline and periodically in 58 patients receiving either bevacizumab plus platinum-based chemotherapy (N=25) or erlotinib (N=33). Results Bevacizumab-treated patients had lower longest diameter at best response compared to the erlotinib group (p=0.011). The longest diameter, tumor volume and density significantly decreased from baseline to best response for the entire cohort and bevacizumab-treated patients; no difference was found in the erlotinib group. Conclusion Treatment with bevacizumab substantially improved tumor metrics between baseline and each cycle of treatment, as well as between baseline and best response, in patients with advanced NSCLC.

Introduction: Nanoparticle albumin-bound (nab)-paclitaxel (nab-P) is approved for the treatment of patients with metastatic breast cancer (MBC) who have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing therapy is not indicated. Real-world evidence on the effectiveness of nab-P is sparse. From this perspective, this non-interventional study was designed to assess the impact of nab-P on the clinical outcomes and the quality of life of patients with MBC in the routine care of Greece. Materials and methods: This multicenter prospective study enrolled consented females with MBC initiated (≤7 days prior to enrollment) on nab-P according to physicians decision. Clinicopathologic parameters and patient-reported outcomes [Functional Assessment of Cancer Therapy-Breast (FACT-B)] were collected at approximately 9-week intervals during the first 12 months of study participation and approximately every 18 weeks thereafter, until the end of the study observation period (maximum 30 months). Results: Between April 2016 and October 2017, 150 eligible patients (99.3% Caucasian) were enrolled in the study in 16 oncology centers. The patients’ median age was 64.5 years (range: 30.7-84.0) and ECOG performance status was 0 in 66.4% and 1 in 26.2%. 45.3% of patients had ≥1 comorbidity (21.3% cardiovascular diseases). The median time elapsed since MBC diagnosis was 22.4 months, while 36.0% of patients were de novo metastatic. The distribution of hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) status was 74.6% HR+/HER2-, 11.9% HR-/HER2-, 11.2% HR+/HER2+, and 2.2% HR-/HER2+. Most commonly occurring metastatic sites were the bones (55.3%), lung (50.0%), and liver (40.0%). Prior taxane-based therapy was annotated in 40.0% of patients. Of the patients, 11.3% received nab-P as first, 36.0% as second, 23.3% as third, and 29.3% as fourth or further treatment line. A median of 6 cycles (range: 1-33) was administered; 42.7% of the patients completed >6 and 22.0% >8 cycles. Dose reductions were required for 26.0% of the patients, mainly due to toxicity. The objective response rate was 26.7% and the clinical benefit rate was 44.0%. After a median follow-up of 19.3 months, 92 patients had progressed and 57 had died (14 without progression). The median progression-free survival (PFS) was 6.2 months [95% confidence interval (CI): 5.2-7.3]. The 6- and 12-month PFS rates were 50.6% and 30.5%, respectively. The median overall survival was 21.1 months (95% CI: 17.2-not estimable). Liver [hazard ratio (HR): 1.81; 95% CI: 1.24-2.66] and lung (HR: 1.53; 95% CI: 1.04-2.25) metastases were associated with a higher risk of progression or death. No statistically significant change in the patients’ baseline FACT-B total score (median: 93.0) was observed. The serious and non-serious adverse event (AE) incidence rates were 12.7% and 48.0%, respectively with a total of 37 grade ≥3 AEs (not including disease progression) reported. Conclusion: This study generated real-world evidence on the effectiveness of nab-paclitaxel; no new safety signals emerged. Citation Format: Anna Koumarianou, Paris Makrantonakis, Flora Zagouri, Christos Papadimitriou, Athina Christopoulou, Epaminontas Samantas, Christos Christodoulou, Amanda Psyrri, Dimitris Bafaloukos, Gerasimos Aravantinos, Pavlos Papakotoulas, Sofia Baka, Charalampos Andreadis, Athanasios Alexopoulos, Iliada Bombolaki, Katerina Kampoli, Sofia Liori, Kiki Karvounis, Alexandros Ardavanis. Real-world multicenter, prospective study of the effects of nab-paclitaxel on clinical outcomes and quality of life of patients with metastatic breast cancer in Greece. The ‘ABReast’ study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-07.

Background: We evaluated the association between pathogenic mutations and overall survival (OS) in patients with cancer referred to Hellenic Cooperative Oncology Group-affiliated Departments. Patients and methods: Patients referred from 12/1980 to 1/2017 had molecular testing (for research) of archival tumor tissue collected at the time of first diagnosis (non-metastatic, 81%; metastatic, 19%). Tumor-specific gene panels (16-101 genes) were used to identify pathogenic mutations in clinically relevant genes. NGS genotyping was performed at the Laboratory of Molecular Oncology, Aristotle University of Thessaloniki. Annotation of mutations was performed at MD Anderson Cancer Center. Results: We analyzed 3,084 patients (median age, 57 years; men, 22%) with sequencing data. Overall, 1,775 (58% of 3,084) patients had pathogenic mutations. The median follow-up was 7.52 years (95% CI, 7.39-7.61). In patients with non-metastatic tumors, after stratification by tumor type, increasing age, higher grade, and histology other than adenocarcinoma were associated with shorter OS. OS was also shorter in patients with pathogenic TP53 (HR=1.36; p

Background Alternative splicing of vascular endothelial growth factor A (VEGFA) results in VEGFAxxxb antiangiogenic isoforms that fail to activate angiogenesis. Bevacizumab, widely used in patients with metastatic colorectal cancer (CRC), binds both VEGFA and VEGFAxxxb isoforms. Patients and Methods Formalin-fixed, paraffin-embedded primary tumors from metastatic CRC patients treated with first-line FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) + bevacizumab (n = 285) or FOLFIRI only (n = 75) were collected. The relative expression of VEGFA121a, 121b, 145a, 145b, 165a, and 165b was assessed with custom TaqMan-MGB assays and quantitative PCR. Results At a median follow-up of 101.5 months, left-sided primary CRC was a favorable prognosticator (median survival, 29.2 vs. 18.2 months; P = .015). Positive high VEGFA145b was an unfavorable factor for progression-free survival (PFS; hazard ratio [HR] = 1.66; 95% confidence interval [CI], 1.13-2.44; P = .009) in patients who received FOLFIRI + bevacizumab, without prognostic significance in FOLFIRI-only patients (HR = 0.70; 95% CI, 0.34-1.44; P = .33). The adverse effect on PFS of 145b was more pronounced in patients with right-sided colon cancer (HR = 2.62; 95% CI, 1.35-5.12; P = .005), especially in those who received bevacizumab (HR = 2.85; 95% CI, 1.31-6.21; P = .008). In patients with right-sided colon primary tumors, isoform 121b correlated with inferior PFS (HR = 1.73; 95% CI, 0.94-3.18; P = .076) and overall survival (OS; HR = 2.0; 95% CI, 1.08-3.72; P = .028). In patients with left-sided primary tumors, positive high 165b correlated with superior PFS (HR = 0.76; 95% CI, 0.59-0.99; P = .044) and OS (HR = 0.68; 95% CI, 0.52-0.90; P = .006). At multivariate analysis, right-sided primary tumor was associated with inferior PFS (HR = 1.28; 95% CI, 1.00-1.64), while 145b consistently retained predictive significance for lack of benefit in PFS with bevacizumab (HR = 1.71; 95% CI, 1.16-2.53). Multivariate analysis for OS showed that VEGFA165b expression was favorable in patients with left-sided but unfavorable in patients with right-sided primary tumors (Pinteraction Conclusion The antiangiogenic isoform VEGFA145b messenger RNA may predict resistance to bevacizumab. Differences in biological relevance and prognostic significance of various VEGFA isoforms were found for right- versus left-sided primary tumors.

Background-aim: SRC, CDKN1B and JAK2 play a crucial role in the coordination and facilitation of cell-signaling pathways controlling a wide range of cellular functions. In the present study, we investigated the prognostic significance and clinical utlity of these biomarkers in metastatic breast cancer (MBC) patients treated with trastuzumab (T). Methods: We assessed SRC, CDKN1B and JAK2 mRNA expression with qRT-PCR (Taqman-MGB assays) on 197 paraffin tumors. PIK3CA mutation status was previously assessed. Relapsed (RMBC) and de novo MBC (dnMBC) patients had received T for metastatic disease only. Tumors were centrally re-assessed for HER2 status. Results: Only 133/197 patients (67.5%) were found to be truly HER2(+). CDKN1B mRNA expression strongly correlated with SRC (rho = 0.71) and JAK2 (rho = 0.54); high CDKN1B was more frequent in RMBC compared to dnMBC (p = 0.001) and in PIK3CA wild-type tumors (p = 0.005). In HER2(+) patients, low CDKN1B conferred higher risk for progression (HR 1.58, 95% CI 1.08-2.32, p = 0.018). In HER2(-) patients, low SRC was associated with longer survival (HR 0.56, 95% CI 0.32-0.99, p = 0.045) and, as a trend, with increased progression-free survival (PFS) (p = 0.067). For PFS, in RMBC, we observed trends for unfavorable low CDKN1B (p = 0.068) and JAK2 (p = 0.086); similarly, in dnMBC for unfavorable low CDKN1B (p = 0.072). Low SRC showed a trend for better survival in RMBC (p = 0.087). Upon multivariable analyses, only PIK3CA mutations strongly predicted for unfavorable PFS in HER2(+) patients (HR 3.37, 95% CI 1.98-5.73, p < 0.001). Low CDKN1B and JAK2 mRNA expression remained unfavorable factors for PFS in dnMBC and RMBC patients (HR 2.36, 95% CI 1.01-5.48, p = 0.046 and HR 1.76, 95% CI 1.01-3.06, p = 0.047, respectively). Conclusions: Low CDKN1B and JAK2 mRNA expression were unfavorable prognosticators in a cohort of T-treated MBC patients previously unexposed to this agent, with distinct impact in de novo and RMBC. Our results highlight biological and clinical differences between de novo and RMBC and suggest that CDKN1B and JAK2, if validated, may serve as prognostic factors potentially implicated in T-resistance, which seems to be associated with distinct pathways in the two MBC settings. Citation Format: Economopoulou P, Kotoula V, Koliou G-A, Papadopoulou K, Christodoulou C, Pentheroudakis G, Koutras A, Bafaloukos D, Papakostas P, Pectasides D, Kotsakis A, Razis E, Samantas E, Kalogeras KT, Economopoulos T, Fountzilas G. Prognostic impact of SRC, CDKN1B and JAK2 expression in metastatic breast cancer patients treated with trastuzumab [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-20.

Simple Summary Data on the prognostic and predictive value of germline cancer predisposing pathogenic/likely pathogenic variants (P/LPVs) in patients with pancreatic ductal adenocarcinoma is limited. This research was a study of germline testing of 62 cancer susceptibility genes in 549 unselected patients with pancreatic cancer. We reported a significant proportion of European patients with pancreatic cancer carrying P/LPVs in clinically significant genes, irrespectively of age, family history or disease stage. Importantly, P/LPVs were identified in pancreatic cancer-associated genes and in homologous recombination repair genes in 4.0% and 7.7% of patients, respectively. The presence of any P/LPVs was associated with improved overall survival univariately; however, it did not retain its independent prognostic significance in multivariate analysis. The presence of P/LPVs in homologous recombination repair genes did not predict benefit from platinum-based treatment. These results should be prospectively validated through universal genetic testing of patients with pancreatic cancer, taking into consideration the administration of newer treatments. Abstract Our aim was to determine the prevalence, prognostic and predictive role of germline pathogenic/likely pathogenic variants (P/LPVs) in cancer predisposing genes in patients with pancreatic ductal adenocarcinoma (PDAC). Germline testing of 62 cancer susceptibility genes was performed on unselected patients diagnosed from 02/2003 to 01/2020 with PDAC, treated at Hellenic Cooperative Oncology Group (HeCOG)-affiliated Centers. The main endpoints were prevalence of P/LPVs and overall survival (OS). P/LPVs in PDAC-associated and homologous recombination repair (HRR) genes were identified in 22 (4.0%) and 42 (7.7%) of 549 patients, respectively. P/LPVs were identified in 16 genes, including ATM (11, 2.0%) and BRCA2 (6, 1.1%), while 19 patients (3.5%) were heterozygotes for MUTYH P/LPVs and 9 (1.6%) carried the low-risk allele, CHEK2 p.(Ile157Thr). Patients carrying P/LPVs had improved OS compared to non-carriers (22.6 vs. 13.9 months, p = 0.006). In multivariate analysis, there was a trend for improved OS in P/LPV carriers (p = 0.063). The interaction term between platinum exposure and mutational status of HRR genes was not significant (p-value = 0.35). A significant proportion of patients with PDAC carries clinically relevant germline P/LPVs, irrespectively of age, family history or disease stage. The predictive role of these P/LPVs has yet to be defined. ClinicalTrials.gov Identifier: NCT03982446.

The mechanism of action of bevacizumab and erlotinib is quite different in the treatment of advanced non-small cell lung cancer (NSCLC). This study sought to compare the two targeted therapies in terms of sequential tumor response metrics.Parameters of radiological tumor response evaluation were assessed at baseline and periodically in 58 patients receiving either bevacizumab plus platinum-based chemotherapy (N=25) or erlotinib (N=33).Bevacizumab-treated patients had lower longest diameter at best response compared to the erlotinib group (p=0.011). The longest diameter, tumor volume and density significantly decreased from baseline to best response for the entire cohort and bevacizumab-treated patients; no difference was found in the erlotinib group.Treatment with bevacizumab substantially improved tumor metrics between baseline and each cycle of treatment, as well as between baseline and best response, in patients with advanced NSCLC.

Vascular endothelial growth factor (VEGF) targeting represents the standard first-line therapy for metastatic renal-cell carcinoma (mRCC), while blocking the mammalian target of rapamycin (mTOR) is effective in relapsed disease. Since continuing blockade of VEGF may be of value, we studied the combination of bevacizumab with temsirolimus in mRCC patients relapsing after first-line treatment. A prospective, phase II study of the combination of bevacizumab (10 mg/kg, every 2 weeks) with temsirolimus (25 mg weekly) in patients with mRCC who failed first-line anti-VEGF treatment. 6-month progression-free survival (PFS) rate was the primary end point. The association of VEGFa, VEGFR2, fibroblast growth factor (FGF) b, platelet-derived growth factor receptor (PDGFR) a and PDGFRb with prognostic factors and outcomes were also studied. 39 patients were enrolled. First-line therapy included: sunitinib (n = 16), bevacizumab/interferon (n = 12), pazopanib (n = 10), sorafenib (n = 1). After a median follow-up of 37 months, 6-month PFS rate was 50.9% [95% confidence interval (CI) 33.8–65.7], median time to progression 6.8 months (95% CI 5.5–9.2) and median overall survival (OS) 18.2 months (95% CI 12.9–27.2). Objective response rate was 27%. The most common AEs were metabolic (33%), renal (8%) and gastrointestinal (GI) (7%). The most common grade 3–5 AEs were GI (18%), infections (14%) and metabolic (25%). Toxicity was the most frequent cause of treatment discontinuation (40%). FGFb levels were associated with OS. In concert with recent data, our study confirms the efficacy of anti-VEGF/anti-mTOR combination in mRCC relapsing after anti-VEGF therapy. Toxicity was considerable leading to high rate of treatment discontinuations. ClinicalTrials.gov: NCT01264341

BACKGROUND/AIM The efficacy of gemcitabine-based chemotherapy in locally advanced/metastatic biliary tract carcinoma is limited. The aim of this trial was to assess the activity of a novel gemcitabine-pazopanib combination in such patients. PATIENTS AND METHODS In this phase II, multicenter trial, patients with histologically/cytologically confirmed biliary tract carcinoma, previously untreated for advanced disease, received 1000 mg/m2 of gemcitabine on days 1 and 8 every 21 days and 800 mg of pazopanib once daily continuously for 8 cycles, followed by pazopanib maintenance. The primary endpoint was objective response rate (ORR). RESULTS A total of 29 patients (median age; 69 years) were enrolled between June 2013 and March 2018. The ORR was 13.8% in the intent-to-treat and 19.1% in the per protocol population. The median progression-free and overall survival were 6.3 and 10.4 months, respectively. CONCLUSION The low response rate precludes further testing of the combination in patients with biliary tract carcinoma.

Background: Tumor-infiltrating lymphocytes (TILs) have been shown to be of prognostic value in several cancer types. In early breast cancer, TILs have a prognostic utility, as well, especially in HER2-positive and triple-negative breast cancer (TNBC). TILs presence is broadly associated with improved survival, however there is controversy regarding TILs subpopulations. In general, T cell infiltration is higher in non-luminal and more aggressive tumors, like the basal-like subtype. Among TILs subpopulations, CD8-positive T cell infiltration is associated with better outcome, whereas high numbers of FOXP3-positive T regulatory cells are associated with worse outcome in ER-positive tumors and better outcome in HER2-positive and TNBC tumors. Patients and Methods: Early breast cancer patients, treated with anthracycline-based chemotherapy within two randomized trials (HE10/97 and HE10/00) were included in the study. We evaluated, by qRT-PCR, 826 macrodissected formalin-fixed paraffin-embedded tumor tissue samples for mRNA expression of CD3, CD8 and FOXP3for potential prognostic significance in terms of disease-free survival (DFS) and overall survival (OS). TILs were evaluated in whole sections as percent of total cells. Results: Median age was 52.7 years, while 54.2% of the patients were postmenopausal and 79.0% ER/PgR-positive. After a median follow-up of 133.0 months, 255 patients (30.9%) had died and 314 (38.0%) had disease progression. All three mRNA markers were positively correlated with TILs (Spearman's r=0.52 for CD3, 0.41 for CD8 and 0.47 for FOXP3, all p-values Conclusions: High CD3 and CD8 mRNA expression in early breast cancer patients is of prognostic value for decreased risk for relapse and, in the future, could potentially be of importance in deciding the most appropriate therapeutic strategy in light of the recent immune-related treatment developments. Citation Format: Tsiatas M, Kalogeras KT, Manousou K, Wirtz RM, Gogas H, Veltrup E, Zagouri F, Lazaridis G, Koutras A, Christodoulou C, Pentheroudakis G, Petraki C, Bafaloukos D, Pectasides D, Kosmidis P, Samantas E, Karanikiotis C, Papakostas P, Dimopoulos M-A, Fountzilas G. Evaluation of the prognostic value of CD3, CD8 and FOXP3 mRNA expression in early breast cancer patients treated with anthracycline-based adjuvant chemotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-03.

Background The advanced lung cancer inflammation index [ALI: body mass index × serum albumin/neutrophil-to-lymphocyte ratio (NLR)] reflects systemic host inflammation, and is easily reproducible. We hypothesized that ALI could assist guidance of non-small-cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICIs). Patients and methods This retrospective study included 672 stage IV NSCLC patients treated with programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy in 25 centers in Greece and Germany, and a control cohort of 444 stage IV NSCLC patients treated with platinum-based chemotherapy without subsequent targeted or immunotherapy drugs. The association of clinical outcomes with biomarkers was analyzed with Cox regression models, including cross-validation by calculation of the Harrell's C-index. Results High ALI values (>18) were significantly associated with longer overall survival (OS) for patients receiving ICI monotherapy [hazard ratio (HR) = 0.402, P < 0.0001, n = 460], but not chemo-immunotherapy (HR = 0.624, P = 0.111, n = 212). Similar positive correlations for ALI were observed for objective response rate (36% versus 24%, P = 0.008) and time-on-treatment (HR = 0.52, P < 0.001), in case of ICI monotherapy only. In the control cohort of chemotherapy, the association between ALI and OS was weaker (HR = 0.694, P = 0.0002), and showed a significant interaction with the type of treatment (ICI monotherapy versus chemotherapy, P < 0.0001) upon combined analysis of the two cohorts. In multivariate analysis, ALI had a stronger predictive effect than NLR, PD-L1 tumor proportion score, lung immune prognostic index, and EPSILoN scores. Among patients with PD-L1 tumor proportion score ≥50% receiving first-line ICI monotherapy, a high ALI score >18 identified a subset with longer OS and time-on-treatment (median 35 and 16 months, respectively), similar to these under chemo-immunotherapy. Conclusions The ALI score is a powerful prognostic and predictive biomarker for patients with advanced NSCLC treated with PD-L1 inhibitors alone, but not in combination with chemotherapy. Its association with outcomes appears to be stronger than that of other widely used parameters. For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy., Highlights • ALI is prognostic and predictive for patients with advanced NSCLC treated with immunotherapy monotherapy, but not chemo-immunotherapy. • Its association with outcomes is stronger than that of other parameters (PD-L1 TPS, NLR, lung immune prognostic index, EPSILoN). • For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy.

Aim: The aim of this study was to evaluate the mRNA expression pattern of growth- and survival-related genes and assess their prognostic significance in patients with advanced pancreatic cancer. Patients and Methods: In total, 98 patients were included in this retrospective translational research study and were evaluated for Kirsten rat sarcoma viral oncogene homolog (KRAS) mutational status, and v-akt murine thymoma viral oncogene homolog 1 (AKT1), AKT serine/threonine kinase 2 (AKT2), AKT serine/threonine kinase 3 (AKT3), cyclin D1 (CCND1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), hepatocellular growth factor receptor (MET), avian myelomatosis viral oncogene homolog (MYC), nuclear factor kappa B subunit 1 (NFKb1), phosphatase and tensin homolog (PTEN) and mechanistic target of rapamycin (FRAP1) genes mRNA expression. Among these patients, 73 received first-line gemcitabine combined with erlotinib (N=57) or gefitinib (N=16). Results: KRAS mutation did not correlate with mRNA gene expression. Unsupervised hierarchical clustering according to mRNA gene expression successfully distinguished four prognostically distinct groups of tumors. Overexpression of all genes was associated with best prognosis, while suppression or heterogeneous expression patterns of the examined genes were associated with expression patterns of growth- and survival-related genes, classifying pancreatic tumors into distinct groups with possibly different outcomes.

Since syndecan-1 is an adhesion molecule involved in tumor invasion and metastasis, we evaluated the relationship between syndecan-1 expression and histopathological features of gastric carcinomas.Syndecan-1 expression was evaluated in 104 gastric carcinomas using immunohistochemistry.High, moderate and low syndecan-1 expression in carcinoma cells was observed in 17/104, 25/104 and 62/104 cases, respectively. High, moderate and low syndecan-1 expression in stromal cells was observed in 5/104, 22/104 and 77/104 cases, respectively. Low epithelial syndecan-1 expression was significantly associated with increased depth of invasion (p=0.034) and lymph vessel invasion (p=0.035). Low stromal syndecan-1 expression was significantly associated with histologic type (intestinal vs diffuse/mixed; p=0.04), increased histologic grade (p=0.04) and large tumor size (p=0.026).Low levels of tumor and stromal syndecan- 1 expression were associated with adverse histopathological parameters in gastric carcinoma. This suggests that syndecan-1 expression may be helpful for assessing the aggressiveness of gastric carcinomas.

Background The clinical relevance of mismatch repair (MMR) status in patients with nonmetastatic cancer across tumour types remains unclear. Our goal was to investigate the prognostic role of MMR deficiency in patients with stage I-III colorectal and endometrial cancer.Methods Patients with nonmetastatic colorectal and endometrial cancer with tumour tissue available for analysis were identified through the Hellenic Cooperative Oncology Group (HeCOG)’s tumour repository. Patients had been referred to Departments of Medical Oncology affiliated with HeCOG. MMR protein expression was evaluated by immunohistochemistry. The primary outcome measure was overall survival (OS).Results From May 1990 to September 2012, 1158 patients with nonmetastatic colorectal (N = 991) and endometrial cancer (N = 167) were identified (median age: 64 years, men: 544). All patients with colorectal and 109 (65%) with endometrial cancer had received adjuvant treatment. MMR deficiency was observed in 114 (11.5%) of colorectal and 80 (47.9%) of endometrial tumours. More commonly deficient proteins were PMS2 (69 patients, 7%) and MLH1 (63 patients, 6.5%) in colorectal cancer and MSH2 (58 patients, 34.7%) in endometrial cancer. Colorectal MMR-deficient (dMMR) tumours were more likely to be right sided (65 % dMMR vs 27 % proficient MMR, pMMR; p < 0.001), high grade (31% vs 15%, χ2, p < 0.001) and with a mucinous component (64% vs 42%, p < 0.001). Endometrial dMMR tumours were more often of endometrioid histology (51.4 % endometrioid vs 20 % serous/clear cell, p = 0.020). Compared with MMR proficiency, MMR deficiency was associated with improved OS in patients with endometrial cancer (HR = 0.38, 95% CI 0.20 to 0.76, p = 0.006), but not in patients with colorectal cancer (HR = 0.73, 95% CI 0.49 to 1.09, p = 0.130). After adjusting for age, stage and grade, MMR deficiency maintained its favourable prognostic significance in patients with endometrial cancer (HR = 0.42, 95% CI 0.20 to 0.88, p = 0.021).Conclusions DMMR was associated with improved outcomes in patients with nonmetastatic endometrial cancer, but not in patients with nonmetastatic colorectal cancer who received adjuvant chemotherapy.

Background/aim Early-stage colorectal cancer (CRC) carries a wide range of survival probabilities. Novel biomarkers in this setting are eagerly awaited. Cancer stem cells (CSCs) are considered one of the reasons for treatment failure. This study sought to determine whether activation of pathways governing the function of CSC's could correlate with treatment outcomes. Materials and methods Tumor specimens from 325 patients were analyzed with immunohistochemistry (IHC) for Hedgehog and Notch pathway activation and results were correlated with prognosis. Results Positive Notch3 protein expression was an unfavorable prognostic factor for disease-free survival (DFS) and overall survival (OS) (HR=2.43, p=0.024 and HR=2.56, p=0.028, respectively). Activation of the Shh pathway showed univariately longer DFS (HR=0.49, p=0.032). Possible crosstalk between the two pathways was indicated. No further associations between pathway activation and outcome were evident. Conclusion Apart from Notch 3, activation of the pathways, as indicated by IHC expression of their components, did not result in differences in terms of DFS or OS.

e14135 Background: CAT is the 2nd leading cause of death in oncology patients and there is need for thrombosis management across the natural history of cancer because of its dynamic nature. Anticoagulant therapy is the cornerstone of prevention and treatment, since thrombosis interferes with cancer treatment, increases health care resource utilization, imposes emotional and economic burden. Methods: A prospective observational study conducted by HeSMO across Greece, aiming to record the clinical practice of CAT prophylaxis in patients with solid tumors. Ambulatory, high risk for thrombosis, active cancer patients who received thromboprophylaxis are enrolled after signing informed consent. Results: Preliminary results are collected from 17 oncology departments. From the 272 enrolled patients, 176 (64.7%) have completed second visit (3-4 cycles of anticancer treatment). Primary cancers included: lung 31.3%, pancreas 26.1%, colorectal 13.6%, gynecological cancers 10.2%, stomach 7.8%, bladder 6.3%, and others.75.6% of the patients had metastatic disease. 1/3 of the patients were smokers or ex-smokers, and 33% underwent surgery. Most of patients (65.9%) were at 1st line treatment and 17.6% at 2nd line. The vast majority (90.3%) were treated with High-Risk for Thrombosis Chemotherapy Agents (HRTCAs) such as cisplatin etc. Regarding Khorana score, 65.1% had ≥2. In particular, 86.7% of patients with Khorana score ≤1 received HRTCAs while 95.4% of patients with score = 2.All patients received thromboprophylaxis, specifically: 93.0% tinzaparin, 5.2% fondaparinux and 1.8% other (enoxaparin, bemiparin) with average duration 5.3±3.1 months. 67.1% of the patients received higher than standard prophylactic doses. 3 patients (1.7%) experienced thrombotic events (2 DVT and 1 PE). These 3 patients had metastases and were treated with HRTCAs. Five grade 1 bleeding events were reported (2.8%). Conclusions: Thromboprophylaxis of CAT is both safe and effective. Oncologists are alerted about CAT negative influences in cancer patients’ prognosis. Apart from Khorana score, factors such as metastases, use of HRTCAs along with drug-drug interactions, increase the LMWHs usage often in higher than prophylactic doses in CAT management. Clinical trial information: NCT03909399.

Introduction Plusieurs etudes de phase II non comparatives ont evalue la vinorelbine orale metronomique (VOM) dans le cancer bronchique metastatique non a petites cellules (CBNPC), mais la petite taille de chaque etude limite leurs conclusions. Objectif Realiser une meta-analyse sur donnees individuelles des patients inclus dans les etudes evaluant la VOM dans les cas de CBNPC metastatique afin de mesurer la survie et la securite du traitement avec ce schema therapeutique. Methodes Les etudes ont ete selectionnees si : – l’administration de vinorelbine par voie orale etait donnee trois fois par semaine ; – avec une dose quotidienne fixe comprise entre 30 et 50 mg ; – la publication etait anterieure au 4 octobre 2018. La base de donnees comprenait 8 variables caracterisant la maladie et la demographie, 3 variables informant sur le schema therapeutique et 12 variables decrivant la survie et la toxicite. Resultats Neuf etudes portant sur 418 patients remplissaient les criteres de selection, 80 % des patients presentaient des criteres de fragilite tel qu’un âge de 75 ans ou plus, ou un indice de performance ECOG (PS) = 2. La survie globale (SG) mediane etait de 8,7 mois (IC95 % : 7,6 a 9,5). Les taux de SG a six mois, un an et deux ans apres le debut du traitement par la vinorelbine etaient respectivement de 64 %, 30,3 % et 8,9 %. Dans le modele de Cox, un PS = 2 et l’anemie quel qu’en soit le grade etaient des determinants significatifs d’une SG plus breve. La survie sans progression mediane etait de 4,2 mois (IC95 % : 3,9–5). A 6 mois et a un an, les taux de SSP etaient respectivement de 35 % et 11,9 %. Dans le modele de Cox stratifie pour la variable « etude », un PS = 2 et un stade IV (vs IIIb) etaient des determinants significatifs d’une PFS plus breve. Pour 40 % des patients, aucune toxicite n’a ete rapportee, alors que 66 autres patients (15,8 %) ont presente une toxicite de grade 3–4. La toxicite la plus frequente etait une anemie de tout grade (35,8 %) qui etait la plus severe avec la dose de 50 mg. Conclusion La vinorelbine orale metronomique est une chimiotherapie active et bien toleree pour le CBNPC metastatique et constitue une option de traitement gerable pour les patients fragiles.

Cutaneous toxicities from novel anticancer treatments are an emerging problem in dermato-oncology. However, the prevalence of those toxicities and necessity of skin consultations are currently unknown. The purpose of our study was to perform an epidemiologic analysis of cutaneous toxicities that were referred to our cutaneous toxicity clinic in Athens, Greece. All patients examined at the oncodermatology department over a 42-month period were included. Gender, age, type of cancer, type of antineoplastic treatment, and type of toxicity were recorded and analyzed. Four hundred fifty-nine patients (182 males, 277 females) with mean age (SD) 60.6 years (13.05) were included in the analysis. Six hundred seventy-two cutaneous toxicities were recorded. Chemotherapy-induced toxicities were the most commonly recorded incidents, with taxanes being the most commonly involved agent. Immune-related adverse events (IRAEs) have steadily increased over the past 3 years. Treatment modifications due to skin toxicities were more common in patients treated with targeted agents and immune checkpoint inhibitors than in those treated with chemotherapy. The toxicities that led to the most treatment modifications were acneiform eruptions and perionychias. The most common IRAEs recorded were psoriasis in 11 patients, followed by pruritus, macular rash, and lichenoid-type eruptions. In addition, 4 interesting cases of IRAEs are discussed. Antineoplastic treatments can lead to a wide range of cutaneous toxicities. Our study underlines the need for a multidisciplinary approach in oncologic patients. The dermatologists’ role is crucial in effectively managing those reactions and preventing antineoplastic drug dose adjustments or discontinuation of treatment.

Background:Metastatic RCC (mRCC) treatment has been revolutionized with 11 approved targeted agents. We report patterns of practice, outcomes and pharmacoeconomic analyses after the introduction of...

Several studies support an important role of angiogenesis in breast cancer growth and metastasis. The main objectives of the study were to investigate the immunohistochemical expression of vascular endothelial growth factor (VEGF) family ligands (VEGF-A and VEGF-C) and receptors (VEGFR1, VEGFR2 and VEGFR3) in breast cancer and their associations with clinicopathological parameters, cancer subtypes/subgroups and patient outcome. Formalin-fixed paraffin-embedded tumor tissue samples were collected from early-stage breast cancer patients treated with anthracycline-based chemotherapy within a randomized trial. Immunohistochemistry was performed on serial 2.5 μm thick tissue sections from tissue microarray blocks. High VEGF-A, VEGF-C, VEGFR1, VEGFR2 and VEGFR3 protein expression was observed in 11.8% (N = 87), 80.8% (N = 585), 28.1% (N = 202), 64.6% (N = 359) and 71.8% (N = 517) of the cases, respectively. Significant associations were observed among all proteins (all p-values

This clinical trial assessed the efficacy and toxicity of panitumumab combined with oxaliplatin and capecitabine as first-line treatment in KRAS exon 2 wild-type metastatic colorectal cancer (mCRC) patients. Patients with exon 2 KRAS wild-type mCRC received panitumumab 9 mg/Kg, oxaliplatin 130 mg/m2, and capecitabine 2000 mg/m2 repeated every 3 weeks. The primary endpoint was objective response rate (ORR, minimum 42 responses). We retrospectively assessed mutations in genes implicated in CRC with massively parallel sequencing; ERBB2 and EGFR amplification with fluorescence in situ hybridization, and tumor-infiltrating lymphocyte density. Among 78 patients enrolled, 45 (57.7%) completed 6 cycles. Most common grade 3–4 toxicities were skin rash (19.2%), diarrhea (18%), and neuropathy (6.4%). Among 5 (6.4%) potentially treatment-related deaths, 2 (2.6%) were characterized toxic. Objective response occurred in 43 (55.1%) of the patients (complete 6.4% and partial response 48.7%; stable 17.9% and progressive disease 7.7%), while 3.8% were non-evaluable and 15% discontinued their treatment early. Additional mutations in KRAS/NRAS/BRAF were found in 11/62 assessable (18%) tumors. After 51 months median follow-up, median progression-free (PFS) was 8.1 and overall survival 20.2 months, independently of KRAS/NRAS/BRAF or PI3K-pathway mutation status. Patients with TP53 mutations (n = 34; 55%), as well as those with left colon primary tumors (n = 66; 85%), had significantly better PFS, also confirmed in multivariate analysis. Although the clinical trial met its primary endpoint, according to the current standards, the efficacy and tolerability of the drug combination are considered insufficient. Extended genotyping yielded interesting results regarding the significance of TP53 mutations. ClinicalTrials.gov identifier: NCT01215539, Registration date: Sep 29, 2010.

The efficacy and safety of the FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) regimen combined with aflibercept has not been studied in the first-line management of patients with metastatic colorectal cancer (mCRC).In the context of a prospective single-arm trial (NCT02129257), patients with mCRC received standard doses of a maximum of 12 cycles of FOLFIRI combined with aflibercept (4 mg/kg body weight delivered intravenously) every 2 weeks, followed by aflibercept maintenance. Endpoints were 12-month progression-free survival rate, efficacy, and toxicity.Seventy-three fit patients were enrolled onto the study between 2014 and 2016. Median relative dose intensities administered were 0.80 for irinotecan and 1.0 for aflibercept. The most common grade 3/4 adverse events were neutropenia (13 patients, 18%), febrile neutropenia (3 patients, 4%), diarrhea (11 patients, 15%), hypertension (19 patients, 26%), proteinuria (8 patients, 11%), infections (8 patients, 11%), and mucositis (6 patients, 8%), with no toxic deaths. The objective response rate was 46.6%, significantly associated with the presence of right-sided primary, synchronous metastases, and a relapse-free interval of 12 months (odds ratio = 3.00, 2.92, and 3.75 respectively, P ≤ .05). Intermediate infiltration by stromal core lymphocytes correlated with progression-free survival (hazard ratio = 0.40, [95% confidence interval (CI), 0.19-0.83], P = .014). At a median follow-up of 24.5 months, 12-month progression-free survival rate was 21.9% (median overall survival 20.9 months [95% CI, 16.6-29], median progression-free survival 8.4 months [95% CI, 7.4-9.3]).The FOLFIRI + aflibercept regimen is active and tolerable; however, it failed to improve historical benchmarks of efficacy in chemonaive patients with mCRC. Preliminary data hint that this regimen has cytoreductive activity in disease with adverse biology.

Small molecules, mainly tyrosine kinase inhibitors, are currently used in various malignancies. Lapatinib, a dual inhibitor of EGFR/HER2 tyrosine kinases, has demonstrated effectiveness in brain metastases from HER2-overexpressing breast cancer. It also appears to sensitize EGFR-expressing cell lines to radiation. To evaluate the efficacy of lapatinib in combination with whole brain radiotherapy (WBRT) in patients with brain metastases from non-small cell lung cancer (NSCLC) and breast cancer, as assessed by volumetric analysis by MRI. 81 patients were treated with WBRT (30 Gy in ten fractions) in combination with lapatinib 1250 mg once daily, followed by lapatinib 1500 mg once daily for a total 6 weeks. 21 patients had primary breast cancer and 60 patients NSCLC. Pre- and post-treatment MRI scans in a compact disk for central volumetric assessment were available for 43 patients. 27 patients (62.8%) achieved partial response, 15 patients (34.9%) had stable disease and only one patient (2.3%) had disease progression. Response was not associated to EGFR protein expression. All 81 patients were assessed for safety. The large majority of the adverse events were mild. Eight deaths occurred, four of which were considered related to the study drugs but there were also other contributing factors. Nine cases of serious infections were observed in eight patients, but they were also receiving dexamethasone. Lapatinib in combination with WBRT in patients with brain metastases from breast cancer and NSCLC is a feasible approach that can be further studied in larger clinical trials.

Background Advanced small cell lung cancer (SCLC) remains a disease with dismal prognosis and new therapeutics are urgently needed. SCLC is notably chemosensitive and first-line chemotherapy with platinum analogs and etoposide is associated with high rates of initial objective responses that unfortunately do not last long. This initial tumor shrinkage provokes neoantigen release in the circulation, sometimes clinically expressed as “tumor lysis syndrome”, rendering thus the disease potently immunogenic. We hypothesized that initial chemotherapy with two cycles of cisplatin-etoposide may trigger tumor lysis and subsequent release of neo-antigens that may in turn enhance immune responses against tumor cells with the addition of an anti-PD-L1 monoclonal antibody, such as avelumab. Trial design PAVE (Phased Avelumab combined with chemotherapy as first-line treatment for patients with advanced small-cell lung cancer) is a Greek, investigator- initiated, single arm open- label phase II study of Avelumab in combination with cisplatin or carboplatin/ etoposide. The study will include an initial safety run-in, open-label, single arm part (Part 1), and the actual phase II study (Part 2). The total number of patients will not change (the safety run-in patients will be included in the final total number of participants). The safety run-in period will not alter the total study timelines, as phase II accrual will follow immediately after the safety run-in. Eligible patients will receive: The standard 1st-line therapy for advanced small cell lung cancer, consisting of: Cisplatin 80 mg/m2 or Carboplatin 5 AUC D1 q three weeks for 4-6 cycles Etoposide 100 mg/m2 D1-D3 every three weeks for 4-6 cycles and Avelumab 10 mg/kg q 2 weeks will be given as a 1 hour intravenous infusion (IV) every two weeks starting from the third chemotherapy cycle until chemotherapy completion and as maintenance treatment every two weeks (q 2 weeks) thereafter until disease progression. Clinical trial identification PAVE study (HE1/17) Identifier: NCT03568097. Legal entity responsible for the study Hellenic Cooperative Oncology Group (HeCOG). Funding Merck KGaA. Disclosure All authors have declared no conflicts of interest.

Background The principles of dose-dense (dd) and sequential (s) chemotherapy (CT) were introduced in the adjuvant setting by HeCOG in 1997. We aimed to explore the long-term clinical benefit and safety of treatment of adjuvant dds-CT in patients (pts) with high-risk BC. Methods We performed a pooled analysis from 6 HeCOG-initiated clinical trials (3 randomized and 3 observational). Patients with operable, early-stage breast cancer received adjuvant treatment with epirubicin, taxane and cyclophosphamide/methotrexate/ fluorouracil (CMF), except from 297 patients included in one study who did not receive taxanes. Granulocyte colony-stimulating factor was given prophylactically with all treatment regimens. The primary study endpoint was 10-year disease-free survival (DFS) rate. Results Between 06/1997 and 04/2013, 4,767 pooled pts were treated with dds-CT (median age 52.9, range 20.9-82.7, postmenopausal: 54%). Patients presented with Hormone receptor (HR)-positive/HER2-negative tumors (56%), HER2-positive tumors (29%) or triple negative breast cancer (TNBC, 15%). Overall, 92.2% of pts completed CT according to study protocol. Grade 4 adverse events were recorded in 356 (8%) pts, mostly neutropenia (81%). Grade 3-4 cardiac adverse events were reported in 6 (0.1%) pts. Six pts succumbed from toxicity during CT including febrile neutropenia (2 pts), acute myocardial infarction (1 pt), infection (1 pt), pulmonary embolism (1 pt) and acute respiratory failure (1 pt). In total, 134 (3%) pts were diagnosed with a secondary cancer; 126 (2.8%) with solid tumors and 16 (0.4%) with a hematologic malignancy. Median follow-up time was 8.9 years (95% CI 8.8-9.1). The 10-year DFS rate was 76% for pts with HR-positive/HER2-negative tumors, 73% with TNBC and 74% for those with HER2-positive tumors (62% and 82% in the pre- and post-trastuzumab era, respectively (p Conclusions dds-CT with epirubicin, taxane and CMF in the adjuvant setting was well-tolerated and was associated with favorable clinical outcomes. Legal entity responsible for the study Hellenic Cooperative Oncology Group (HeCOG). Funding Hellenic Cooperative Oncology Group (HeCOG). Disclosure E. Fountzilas: Travel / Accommodation / Expenses: K.A.M ONCOLOGY / HEMATOLOGY; Travel / Accommodation / Expenses: Merck; Shareholder / Stockholder / Stock options: Deciphera. G. Pentheroudakis: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (institution): Roche; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Amgen; Leadership role, Research grant / Funding (institution): Boehringer; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Merck; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Leadership role: Bristol-Myers Squibb; Advisory / Consultancy: MSD; Leadership role: Enorasis. C. Christodoulou: Advisory / Consultancy: Merck; Advisory / Consultancy: Genesis Pharmaceuticals; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Sanofi. A. Koutras: Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Genesis; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Merck Serono; Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Amgen. E. Samantas: Advisory / Consultancy: Merck; Advisory / Consultancy: MSD; Advisory / Consultancy: Asta-Zeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: Genesis. G. Aravantinos: Advisory / Consultancy: Novartis; Advisory / Consultancy: BMS; Advisory / Consultancy: Roche Hellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: Genesis Pharma; Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer. P. Papakostas: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Merck; Advisory / Consultancy: Genesis Pharmaceuticals. A. Psyrri: Honoraria (institution), Advisory / Consultancy: Amgen; Honoraria (institution), Advisory / Consultancy: Merck Serono; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy: MSD; Research grant / Funding (institution): Kura. P.A. Kosmidis: Honoraria (self): Novartis; Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Genesis. A. Koumarianou: Advisory / Consultancy: Genesis Pharma; Honoraria (self): Pfizer; Speaker Bureau / Expert testimony: Roche; Research grant / Funding (self): Merck; Travel / Accommodation / Expenses: MSD. E. Razis: Honoraria (self), Advisory / Consultancy: Novartis; Travel / Accommodation / Expenses: Genesis Pharmaceuticals; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Genekor. H. Gogas: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): MSD Oncology; Honoraria (institution), Advisory / Consultancy: Amgen; Honoraria (institution), Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Pierre-Fabre. G. Fountzilas: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche; Honoraria (self): AstraZeneca. All other authors have declared no conflicts of interest.

The aim of the study was to evaluate the association of vascular endothelial growth factor (VEGF) genotypes with treatment efficacy in a phase II trial. This study evaluated weekly docetaxel, as first-line treatment for metastatic breast cancer. Existing data from in vitro and animal model experiments suggest that docetaxel at low doses has anti-angiogenic activity. DNA was extracted from blood samples of 86 patients participating in the trial. Genotyping was performed for selected single-nucleotide polymorphisms (SNPs; VEGF-2578, -1498, -1154, and +936). Moreover, due to the highly polymorphic nature of the studied areas, we were able to analyze additional registered SNPs. All candidate genotypes were evaluated for associations with overall survival (OS), progression-free survival (PFS) and response rate. The VEGF-1154 GG genotype was more frequent in patients not responding to treatment compared with responders (42.9% vs 0.0%, P=0.048). Moreover, the VEGF-2578 AA genotype was associated with longer PFS compared with CC (hazard ratio (HR)=0.40; 95% confidence interval (CI) 0.17-0.98; pairwise P=0.0457). Patients with the VEGF-1190 GG genotype demonstrated shorter PFS compared with those with the alternative genotypes (GA and AA) combined (HR=3.85; 95% CI: 1.20-12.50; P=0.0224). In addition, the VEGF-2551/-2534 homozygous del18bp and VEGF-2430/-2425 homozygous ins1bp genotypes were associated with worse PFS compared with no deletion and no insertion, respectively (HR=2.49; 95% CI: 1.02-6.07; pairwise P=0.0442 and HR=2.57; 95% CI: 1.05-6.27; pairwise P=0.0385, respectively). Furthermore, patients with the VEGF-1498 CC genotype exhibited longer median OS compared with those with the alternatives genotypes (CT and TT) combined (HR=0.27; 95% CI: 0.08-0.89; P=0.0311). In multivariate analysis, the VEGF-2578 AA genotype retained its significance (P=0.0220) for PFS. Our results support the association of specific VEGF genotypes with clinical outcome in patients with metastatic breast cancer treated with a potentially anti-angiogenic regimen, such as weekly docetaxel. However, current results should be validated prospectively in larger cohorts.

Gastric cancer is a relatively common malignancy. Recently, the presence of the human epidermal growth factor receptor 2 (HER2) was identified as a molecular target in a proportion of patients who benefited from the addition of appropriate anti-HER2 treatments. Our study explored the clinical and prognostic role of known HER family members, human epidermal growth factor receptor 1 (EGFR or HER1), HER2, HER3 and HER4.Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 249 gastric cancer patients were studied by immunohistochemistry for protein expression of EGFR, HER2, HER3 and HER4.Of the 249 evaluable patients, 32 did not have complete data of treatment details and/or follow-up and were excluded from the survival analyses. Of the 217 patients with complete treatment and follow-up data, 178 were operated and treated for early disease (group 1), while 39 for advanced disease (group 2). The frequency of positive EGFR, HER2, HER3 and HER4 protein expression in all patients was 17.5%, 11.8%, 14.8% and 32.9%, respectively. There were no differences in protein expression of any of the markers between the two groups. There were, however, statistically significant associations between HER4 and all other HER family members, as well as between HER2 and HER3 expression. Of note, EGFR-positive membranous protein expression was significantly associated with the presence of lymphovascular invasion (p=0.027) and HER3 and HER4 negative cytoplasmic protein expression with well/moderately-differentiated tumors (p=0.030 and p=0.014, respectively). None of the HER family members were of prognostic value for OS in univariate analysis.The present study confirmed the known protein expression frequencies of HER family members in gastric cancer in a Greek population. Several associations were observed among the HER family members and between clinicopathological characteristics and HER family members. Further research is needed on their exact prognostic role, as well as their therapeutic targeting.

e18868Background: Cancer has multiple processes that increase thrombogenicity. Thrombosis is the 2nd cause of death in cancer patients. CAT is common, could delay anti-cancer therapy and increase c...