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Background Abiraterone (Abi), enzalutamide (Enz) and docetaxel (Doc) are all approved first-line (1L) treatment options for mCRPC. However, the optimal treatment sequence has not been established yet. In the present analysis, we explored the outcomes of pts treated with 1L Doc or Abi/Enz in the prospective PROREPAIR-B cohort study (NCT03075735). Methods We assessed the impact of 1L treatment options (Doc vs Abi/Enz) on progression-free survival to 1L therapy (PFS) and overall survival (OS). Uni- (UV) and multivariable (MV) Cox-regression models were used. MV model covariates included age (≥75 years), local therapy, Gleason Score, visceral metastases, metastases at diagnosis, phosphatase alkaline (ALP) (≥ULN), lactate dehydrogenase (LDH) (≥ULN), haemoglobin (Hb) (≤LNL), albumin (≤LNL) and ECOG performance status. Results Of 419 pts enrolled in the study, 406 received 1L Doc (n = 188) or Abi/Enz (n = 218). Overall, pts receiving Doc were younger (p = 0.002), had higher rates of visceral metastases (17.6% vs 8.7%, p = 0.008), ALP (52.1% vs 40.4%, p = 0.018), LDH (48.1% vs 31.2%, p Conclusions Pts treated with 1L Doc had worse baseline prognostic features. Despite a longer PFS was observed in pts treated with 1L Abi/Enz vs Doc, no difference in OS was found between the treatment sequences. Similar results were observed in the elderly population. Biomarker-driven pts selection is needed to identify the optimal sequence. Clinical trial identification NCT03075735. Legal entity responsible for the study Centro Nacional de Investigaciones Oncologicas (CNIO). Funding Unrestricted grant from Fundacion Cris Contra el Cancer; three investigator awards from the Prostate Cancer Foundation (C.C.P. [2013], D.O. [2014], and E.C. [2017]); and three grants from Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III (No. PI13/01287 and PI16/01565 to D.O. and No. PI15/01471 to P.L.). During the conduct of this study, E.C., D.O., P.N., and L.M-P. were supported by grants from Ministerio de Economia, Industria y Competitividad (No. JCI-2014-19129 [E.C.], No. RYC-2015-18625 [D.O.], No. SVP-2013-067937 [P.N.], No. SVP-2014-068895 [L.M.]); D.O. was also funded by a Return fellowship from Fundacion Cientifica de la Asociacion Espanola Contra el Cancer, 2012-2015; N.R.L. and R.L., by grants from Instituto de Salud Carlos III (No. CM14-00200 to N.R.L. and No. CM17-00221 [R.L.]); and Y.C., by a grant from Ministerio de Educacion, Cultura y Deportes (No. FPU15/05126). C.C.P. was supported by a congressional-designated medical research program award (No. CMRP-PC131820). Disclosure C. Cattrini: Travel / Accommodation / Expenses: Novartis, Ipsen. N. Romero Laorden: Honoraria (self): MSD, Sanofi-Aventis, Astellas, Janssen-Cilag; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, PharmaMar; Research grant / Funding (institution): Bayer, Astellas, Janssen, Sanofi. E. Castro: Honoraria (self): Astellas Pharma, Janssen-Cilag, AstraZeneca, Bayer, Pfizer; Advisory / Consultancy: Bayer, Janssen-Cilag; Research grant / Funding (institution): Janssen-Cilag, AstraZeneca, Bayer; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, Astellas Pharma. I. Garcia-Carbonero: Advisory / Consultancy: Janssen Oncology, Astellas Pharma, Bayer, Sanofi; Travel / Accommodation / Expenses: Astellas Pharma, Janssen, Sanofi, Bayer. J.M. Piulats: Advisory / Consultancy: Janssen Oncology, Astellas Pharma, VCN Biosciences, Clovis Oncology, Roche, Genentech, Bristol-Myers Squibb, Merck Sharp & Dohme; Research grant / Funding (institution): Bristol-Myers Squibb, AstraZeneca, MedImmune, Merck Sharp & Dohme, Pfizer, EMD Serono, Incyte, Janssen Oncology; Travel / Accommodation / Expenses: Janssen Oncology, Roche, Bristol-Myers Squibb. J. Puente: Advisory / Consultancy: Pfizer, Astellas Pharma, Janssen-Cilag, Merck Sharp & Dohme, Bayer, Roche, Bristol-Myers Squibb, AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Ipsen, Eisai, EUSA Pharma, Sanofi; Speaker Bureau / Expert testimony: Pierre Fabre, Celgene, Kiowa, Novartis, Lilly; Research grant / Funding (institution): Astellas Pharma, Pfizer; Research grant / Funding (institution): Pfizer, Roche, Janssen-Cilag. B. P. Valderrama: Honoraria (self): Pierre Fabre, Astellas Pharma, Novartis, Bristol-Myers Squibb, Ipsen; Advisory / Consultancy: Astellas Pharma, Novartis, Pfizer, Pierre Fabre, Bayer, Sanofi, Bristol-Myers Squibb, Roche, Ipsen; Travel / Accommodation / Expenses: Janssen-Cilag, Bristol-Myers Squibb. E. Gonzalez Billalabeitia: Travel / Accommodation / Expenses: Bristol-Myers Squibb, Pfizer, Janssen-Cilag, Astellas Pharma, Sanofi. R. Morales Barrera: Honoraria (self): MSD, Sanofi, AstraZeneca, Asofarma, Johnson and Johnson, Roche/Genentech; Advisory / Consultancy: MSD, Sanofi, AstraZeneca, Asofarma, Johnson and Johnson, Roche/Genentech; Speaker Bureau / Expert testimony: MSD. Sanofi, AstraZeneca, Asofarma, Johnson and Johnson; Research grant / Funding (institution): AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, INC, Astellas Pharma., AstraZeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim Espana, S.A., Bristol-Myers Squibb Intern; Travel / Accommodation / Expenses: MSD, Roche/Genentech, Lilly, Clovis Oncology, Bayer, Johnson and Johnson, Astellas Pharma, AstraZeneca. R. Lozano Mejorada: Honoraria (self): Roche, Janssen-Cilag, Bayer; Research grant / Funding (institution): Bayer, Janssen-Cilag; Travel / Accommodation / Expenses: Roche, Janssen-Cilag, Astellas Pharma. R. Luque: Honoraria (self), Travel / Accommodation / Expenses: Janssen-Cilag, Sanofi Aventis, Astellas Medivation, Roche, Novartis, Pfizer, Bristol-Myers Squibb, EUSA Pharma. E. Martinez Ortega: Honoraria (self), Travel / Accommodation / Expenses: Sanofi Aventis, Roche, Pfizer Bristol Mayers Squibb, EUSA Pharma and IPSEN. J.A. Arranz Arija: Honoraria (self): Novartis MSD Oncology Janssen-Cilag EUSA Pharma Astellas Pharma Bristol-Myers Squibb; Advisory / Consultancy: Pfizer Astellas Pharma Janssen-Cilag Novartis Bayer Ipsen MSD Oncology Bristol-Myers Squibb EUSA Pharma; Research grant / Funding (institution): Novartis Pierre Fabre Bristol-Myers Squibb; Travel / Accommodation / Expenses: Bristol-Myers Squibb Janssen-Cilag MSD Oncology Pfizer. E. Gallardo Diaz: Honoraria (self): Astellas Pharma, Roche, Bristol-Myers Squibb, Novartis; Advisory / Consultancy: Pfizer, Bayer Schering Pharma, Janssen Oncology, Astellas Pharma, Roche, Bristol-Myers Squibb, Sanofi, Ipsen, Eisai, Rovi, Daiichi Sankyo, EUSA Pharma; Speaker Bureau / Expert testimony: Rovi, LEO Pharma, Menarini, Bristol-Myers Squibb, Ipsen, Astellas Pharma, Roche, Daiichi Sankyo; Travel / Accommodation / Expenses: Pfizer, Astellas Pharma, Pierre Fabre, Bayer Schering Pharma, Bristol-Myers Squibb, Eisai, Janssen, Roche. E. Almagro Casado: Speaker Bureau / Expert testimony: MSD; Travel / Accommodation / Expenses: Bristol-Myers Squibb. M.J. Mendez Vidal: Advisory / Consultancy: Janssen-Cilag, Pfizer, Astellas Pharma, Sanofi, Bayer, Bristol-Myers Squibb, Novartis, Roche; Travel / Accommodation / Expenses: Janssen-Cilag, Pfizer, Astellas Pharma, Bristol-Myers Squibb. D. Olmos Hidalgo: Speaker Bureau / Expert testimony: Astellas, Bayer, Janssen, Sanofi; Advisory / Consultancy: Astellas, AstraZeneca, Bayer, Genentech, Janssen, Clovis; Research grant / Funding (institution): Astellas, AstraZeneca, Bayer, Genentech/Roche, Janssen (Incl.Aragon), Medivation/Pfizer, Tokai, MSD, GSK; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Ipsen. D. Lorente: Honoraria (self): Janssen-Cilag, Bayer, Astellas Pharma, Sanofi; Advisory / Consultancy: Janssen-Cilag, Bayer, Sanofi; Travel / Accommodation / Expenses: Sanofi, Astellas, Janssen-Cilag, Celgene. All other authors have declared no conflicts of interest.

Background Cabazitaxel is used in the treatment of metastatic prostate cancer. It is not a substrate of P-glycoprotein, which is involved in cellular detoxification of chemotherapeutic agents and in the expulsion of drugs at blood-brain barrier. Our objectives are to test Cabazitaxel in vitro in malignant neural cell lines such as glioblastoma, anaplastic glioma and neuroblastoma, and to find any predictor of response that allows us to select potential responder patients in glioblastoma multiforme and other neural tumors. Methods Cell lines A172 (glioblastoma, p53 wild type), LN229 (glioblastoma, p53 mutated), SF268 (anaplastic glioma, p53 mutated) and SK-N-SH (neuroblastoma, p53 wild type) were cultured in 48-well plates and increasing doses of Cabazitaxel were tested (0.1, 0.5, 1, 5, 10, 25, 50, 100μM). After 48hours of treatment, the proliferation values were studied by spectrophotometric assays. Also, gene expression studies of the MMR complex (miss-match repair) were performed by RT-qPCR for the primers of MLH1, MSH2, MSH3, MSH6, PMS2 genes. We also analyzed the expression of CD133 marker by RT-qPCR assays. A PCR study with Bisulfite kit was carried out to detect the promoter methylation of MGMT. Results IC50 values at 48hours were 13.76μm in SF268, 6.77μm in SK-N-SH, 2.88μm in LN 229 and 1.34 in A172. The expression values of MMR complex proteins were significantly higher in line A172 (relative value 1), followed by line LN229 (0.25) and negative in lines SK-N-SH and SF268. The methylation of MGMT promoter was positive in lines A172 and LN229. Finally, the expression of CD133 was higher in A172 (0.6), followed by LN229 (0.4), SK-N-SH (0.2) and SF268 (0). Pearson correlation coefficient for the relationship between CD133 expression and IC50 values is -0.96. Conclusions 1. Glioblastoma, anaplastic glioma and neuroblastoma cell lines have a high sensitivity to Cabazitaxel in vitro. 2. Cell lines with MGMT methylation and MMR expression (A172 and LN 229) are the most sensitive. Of them, line A172 presents a p53 wild type, and therefore, a greater sensitivity to Cabazitaxel. 3. The expression of CD133 correlates inversely with the values of IC50 to Cabazitaxel, and may also be a predictor of response. Legal entity responsible for the study UGR. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Aim: Cabazitaxel (Cab) is a novel tubulin-binding taxane active in preclinical models against docetaxel-sensitive and resistant tumors. Cab is approved for the treatment of metastatic castration resistant prostate cancer (mCRPC) after docetaxel failure; however, its activity against other cancers remains unexplored. SOGUG 2011-04 is a phase II clinical trial designed to explore the efficacy of Cab in advanced genitourinary TCC after progression to a platinum-based regime. As part of this trial, a pharmacogenetic study to identify single-nucleotide polymorphisms (SNPs) predictive of Cab toxicity and response was conducted. Methods: DNA was extracted from blood samples from 45 patients in this trial. Nine key SNPs in genes involved in the pharmacokinetic and pharmacodynamic pathways of Cab (CYP3A4 rs35599367; CYP3A5 rs776746; CYP2C8 rs11572080 and rs1113129 ABCB1 rs1045642, rs1128503 and rs2032582; TUBB1 rs6070697 and rs463312) were genotyped using standard techniques. Logistic regression was used to study toxicity and response, and Cox regression to analyze progression free survival (PFS) and overall survival (OS), using an additive genetic model. Preliminary results are presented. Results: CYP3A5 rs776746 (splicing defect) protected against gastrointestinal (GI) toxicity (OR = 0.06, 95%CI = 0.007-0.63, P = 0.018) and was associated with reduced PFS (HR = 4.4, 95%CI = 1.6-11.7, P = 0.0032). Adjusting for patient prognosis, according to Bellmunt's classification, did not change the results. Furthermore ABCB1 rs1128503, rs1045642 and rs2032582 were associated with the total number of Grade 3-4 toxicity events (P values of 0.009, 0.041, and 0.043, respectively, multivariable analysis). TUBB1 Q43P missense polymorphism was associated with reduced OS (P = 0.0023) although only three patients carried this variant. Conclusions: Polymorphisms in CYP3A5 may define a subset of patients with decreased Cab activity resulting in less GI adverse events and shorter PFS. Additionally, variation in ABCB1 may be associated with the severity of Cab toxicity. These results need to be validated in larger and independent series but suggest potential markers for Cab treatment optimization. * This study has been supported by an unrestricted educational grant of Sanofi-Aventis to the Spanish GU Oncology Group (SOGUG) Disclosure: I. Duran: has participated in compensated Advisory Boards for Sanofi-Aventis; M. Climent: has participated in compensated Advisory Boards for Sanofi-Aventis. All other authors have declared no conflicts of interest.

Primary tumor location was pancreas in 13 pts (25.5%), lung in 11 pts (21.6%), small or large intestine in 8 pts (15.7%), appendix in 5 pts (9.8%), and other locations in 14 pts (27.5%). Results: Thirty-two pts had low grade (Ki67 20%). 49% (25) of the pts were metastatic at diagnosis. Octreoscan was positive in 15 pts with well-differentiated tumors (low and intermediate grade) and in 3 with poorly differentiated tumors (high grade). Resection of the tumor was possible in 24 pts (75%) with low-grade, three (42.9%) with intermediate and 2 (16.7%) with high grade tumors (Chi squared test, p = 0.002). All high grade NETs were treated with chemotherapy (CT) with cisplatin-etoposide. Only 8 low grade tumors and 5 intermediate grade tumors were treated with CT. Eighteen pts with low grade, 4 with intermediate and 1 with high grade tumor were treated with somatostatin analogues. Median survival was 31.36 months for pts with low grade tumors, 21 months for those with intermediate grade and 14.63 months for high grade tumors, with statistically significant differences (Chi square test, p = 0.002). Conclusion: Grade of differentiation, defined by the expression of cell proliferation marker Ki 67 protein, determines differences in the therapeutic strategy of NETs. Our results coincide with the literature regarding the significant correlation among grade of differentiation and survival in pts with NETs. It is established as the main prognostic factor that also modifies the therapeutic approach.

Background: Bevacizumab has efficacy in first-line treatment of advanced colorectal cancer. The overall response with Bevacizumab is low in some studies. Not know the ideal method of assessing response to therapy with bevacizumab. Metabolic imaging of tumor viability with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and simultaneous anatomic localization provided by low-dose non-enhanced computed tomography (CT), can be obtained in a combined modality FDG-PET/CT scan. The purpose of this study was to evaluate the possible contribution of FDG-PET/ CT as a surrogate marker to evaluate treatment response in patients with metastatic colorectal cancer (mCRC) who had been treated with bevacizumab and standard chemotherapy. Methods: Retrospective analysis of 28 patients with advanced colorectal cancer who had been treated in the Hospital Universitario Virgen de las Nieves in Granada. Analyses included all patients who initiated bevacizumab in combination with either first-line oxaliplatin or irinotecan based regimens. FDG-PET/CT scans were performed before the start of the treatment and after six cycles of therapy. Results were compared to concurrent contrast-enhanced CT. Response to treatment was determined according to RECIST size criteria obtained from data from thin (3-5mm) slice CT, and changes in uptake of 18F-FDG uptake on PET. Results: A total of 28 patients were evaluated. Overall, 22 patients had favorable response to treatment, and only 6 had progression of disease. Complete response (CR) was evident on FDG-PET in 6/28 (21,4%) patients whereas only 5 were deemed CR by CT and partial response (PR) in 15/28 (64,3%) with both techniques. Similarly, only 1/ 28 (3,6%) lesion appeared stable by FDG-PET and CT criteria. Progression of disease (PT) was evident on FDG-PET in 6/28 (21,4%) patients whereas only 5 were deemed PT by CT. There was a strong correlation between metabolic response (changes in SUV) and objective response (r = 0.81, P