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Resumen Introduccion El papel de la quimioterapia adyuvante (QTAdy) en el tumor vesical musculo-invasivo sigue siendo controvertido actualmente. Objetivo Evaluar el efecto de la QTAdy en la supervivencia cancer especifica del tumor vesical musculo-invasivo tras cistectomia radical (CR). Material y metodos Analisis retrospectivo de 292 pacientes diagnosticados de tumor vesical urotelial tratados con CR entre 1986-2009 con estadio pT3-4pN0/+cM0, divididas en dos cohortes:185(63,4%) pacientes tratados con QTAdy y otra con 107(36,6%) sin QTAdy. Mediana de seguimiento de 40,5 meses (IQR 55-80,5). Analisis comparativo con test Chi cuadrado y t Student/ANOVA. Calculo de supervivencia con el metodo de Kaplan-Meier y test de long-rank. Analisis multivariante (regresion de Cox) para identificar variables predictoras independientes de mortalidad cancer especifica (MCE). Resultados El 42,8% de la serie presento afectacion ganglionar tras CR. Al finalizar el seguimiento, 22,9% estaban libres de tumor vesical y 54,8% habian fallecido por esa causa. La mediana de supervivencia cancer especifica fue de 30 meses. No se observaron diferencias significativas en supervivencia cancer especifica en funcion del tratamiento con QTAdy en pacientes pT3pN0 (p = 0,25) ni pT4pN0 (p = 0,29), pero si en pT3-4pN+ (p = 0,001). En el analisis multivariante se identificaron el estadio patologico (p = 0,0001) y el tratamiento con QTAdy (p = 0,007) como factores pronosticos independientes de MCE. La QTAdy redujo el riesgo de MCE (HR:0,59, IC95% 0,40-0,87, p = 0,007). Conclusiones El estadio pT y pN se identificaron como variables predictoras independientes de MCE tras CR. La administracion de QTAdy en nuestra serie se comporto como factor protector reduciendo el riesgo de MCE, aunque en el analisis por estadios, unicamente los pacientes pN+ se vieron beneficiados.

Introduction Currently, the role of adjuvant chemotherapy (ADJ) in muscle invasive bladder tumor (MIBC) remains controversial. Objective To evaluate the effect of ADJ on cancer specific survival (CSS) of MIBC after radical cystectomy (RC). Material and methods Retrospective analysis of 292 patients diagnosed with urothelial bladder tumor (BT) pT3-4pN0/+ cM0 stage, treated with RC between 1986-2009. Total cohort was divided in two groups: 185 (63.4%) patients treated with ADJ and 107 (36.6%) without ADJ. Median follow-up was 40.5 months (IQR 55–80.5). Comparative analysis was performed with Chi-square test and Student’s t test/ANOVA. Survival analysis was carried out with the Kaplan–Meier method and log-rank test. Multivariate analysis (Cox regression) was made to identify independent predictors of cancer-specific mortality (CSM). Results 42.8% of the series presented lymph node involvement after RC. At the end of follow-up, 22.9% were BC-free and 54.8% had died due to this cause. The median CSS was 30 months. No significant differences were observed in CSS regarding the treatment with ADJ in pT3pN0 (p = .25) or pT4pN0 (p = .29) patients, but it was significant in pT3-4pN+ (p = .001). Multivariate analysis showed pathological stage (p = .0001) and treatment with ADJ (p = .007) as independent prognostic factors for CSM. ADJ reduced the risk of CSM (HR:0.59,95%CI 0.40–0.87, p = .007). Conclusions pT and pN stages were identified as independent predictors of CSM after RC. The administration of ADJ in our series behaved as a protective factor reducing the risk of CSM, although only pN + patients were benefited in the stage analysis.

Introduction and objectives Nodal prostate cancer recurrence is a challenging scenario. Current guidelines recommend the use of androgen deprivation therapy, tailored treatment or clinical trials. We studied the impact of Salvage lymph node dissection in selected patients. Material and methods We retrospectively reviewed records of 23 consecutive patients with prostate cancer and previous Radical prostatectomy or Radiotherapy who underwent SLND from December 2005 to November 2015. Results We found that in patients that showed biochemical response the introduction of ADT was delayed 14.9 months compared to patients that did not responded (2.8 months) p = 0.00026. Furthermore although statistical significance was not reached ( p = 0.072) PSA-DT could be a potential prognostic factor of radiological recurrence since patients with PSA-DT Conclusions Salvage lymph node dissection is a potential treatment that could delay ADT in selected patients.

Resumen Introduccion y objetivos La recidiva ganglionar en el cancer de prostata es un escenario terapeutico controvertido. Las guias clinicas recomiendan el uso de terapia hormonal, tratamiento «a la carta» o incluir en ensayos clinicos. Estudiamos en el presente estudio el impacto de la linfadenectomia de rescate en pacientes seleccionados. Material y metodos Revisamos retrospectivamente a 23 pacientes consecutivos con cancer de prostata tratados mediante prostatectomia radical o radioterapia externa, a quienes se les practico linfadenectomia de rescate desde diciembre del 2005 hasta noviembre del 2015. Se realizo analisis univariante y bivariante para evaluar la relacion entre factores de riesgo y respuesta a la linfadenectomia. Resultados Encontramos que en los pacientes con respuesta bioquimica; la hormonoterapia fue retrasada 14,9 meses comparandolo con los que no respondieron (2,8 meses), p = 0,00026. A pesar de que no se alcanzo la significacion estadistica (p = 0,072), el tiempo de duplicacion de PSA podria ser un factor pronostico de recidiva radiologica ya que los pacientes con tiempo de duplicacion Conclusiones La linfadenectomia de rescate es un tratamiento que puede retrasar el uso de hormonoterapia en pacientes seleccionados.

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.

The International Metastatic Renal-Cell Carcinoma Database Consortium prognostic classification for patients treated with first-line tyrosine kinase inhibitors did not include patients treated with pazopanib. A validation for this subset is presented in a nation-wide multicenter observational and externally monitored trial (SPAZO), which included 278 patients treated with first-line pazopanib.Patients with metastatic renal carcinoma (mRCC) treated with first-line pazopanib were not included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. SPAZO (NCT02282579) was a nation-wide retrospective observational study designed to assess the effectiveness and validate the IMDC prognostic model in patients treated with first-line pazopanib in clinical practice. Data of 278 patients, treated with first-line pazopanib for mRCC in 34 centres in Spain, were locally recorded and externally validated. Mean age was 66 years, there were 68.3% male, 93.5% clear-cell type, 74.8% nephrectomized, and 81.3% had ECOG 0-1. Metastatic sites were: lung 70.9%, lymph node 43.9%, bone 26.3%, soft tissue/skin 20.1%, liver 15.1%, CNS 7.2%, adrenal gland 6.5%, pleura/peritoneum 5.8%, pancreas 5%, and kidney 2.2%. After median follow-up of 23 months, 76.4% had discontinued pazopanib (57.2% due to progression), 47.9% had received second-line targeted therapy, and 48.9% had died. According to IMDC prognostic model, 19.4% had favourable risk (FR), 57.2% intermediate risk (IR), and 23.4% poor risk (PR). No unexpected toxicities were recorded. Response rate was 30.3% (FR: 44%, IR: 30% PR: 17.3%). Median progression-free survival (whole population) was 11 months (32 in FR, 11 in IR, 4 in PR). Median and 2-year overall survival (whole population) were 22 months and 48.1%, respectively (FR: not reached and 81.6%, IR: 22 and 48.7%, PR: 7 and 18.8%). These estimations and their 95% confidence intervals are fully consistent with the outcomes predicted by the IMDC prognostic model. Our results validate the IMDC model for first-line pazopanib in mRCC and confirm the effectiveness and safety of this treatment.

Brain metastases of testicular germ cell tumor (TGCT) are a rare event. Prognostic is poor and there is not much evidence on optimal management of these patients. A review of case records of germ cell tumor patients within the Spanish Germ Cell Cancer Group data base from 1994 to 2012 was conducted. Thirty-three out of 6,200 cases (0.5 %). Nineteen patients (57 %) group 1: synchronous, 13 (40 %) group 2: metachronous and only one developed brain metastasis during cisplatin-based chemotherapy (excluded from the analysis). Median serum BHCG levels at initial diagnosis was higher in group 1, whereas elevated AFP serum levels were more common in group 2. Histology in the primary tumor: chorionic carcinoma for group 1 versus embryonal carcinoma for group 2. Mainly solitary brain metastasis in group 2 (54 versus 21 %, respectively). The median overall survival from the diagnosis of central nervous system involvement was 16 months for group 1 (CI 95 % 13.9-18) and 23 months (95 % CI 0-165) for group 2 (log rank p = 0.84). Long-term survivors were practically identical in the two groups (38.9 % group 1 versus 38.5 % group 2). Regardless of the timing of brain metastasis, those patients that achieved complete response to the treatment had better survival (log rank p 0.003). Although some distinctive clinical characteristics have been found between patients with synchronous versus metachronous brain metastasis from TGCT, the timing of brain metastasis did not seem to have prognostic influence, but due to the retrospective nature of the analysis and the results should be interpreted with caution.

J.A. Arranz Arija, B. Perez-Valderrama, J.L. Gonzalez-Larriba, A. Rodriguez Sanchez, I. Chirivella, A. Pinto, R.D. Garcia Marrero, G. Rubio, J.M. Jurado Garcia, P. Borrega, M. Lazaro Quintela, D.E. Castellano, C. Suarez Rodriguez, J.A. Meana Garcia, J.J. Lambea-Sorrosal, P. Gajate, M.J. Juan Fita, J.L. Puertas, R. Garcia Dominguez, J.C. Villa Guzman. Hospital General universitario Gregorio Maranon, Medical Oncology Service, Madrid, Spain; Hospitales Universitarios Virgen del Rocio, Medical Oncology Service, Seville, Spain; Hospital Clinico San Carlos, Medical Oncology Service, Madrid, Spain; Hospital Universitario de Leon, Medical Oncology Service, Leon, Spain; Hospital Clinico Universitario, Medical oncology Service, Valencia, Spain; Hospital Universitario La Paz, Medical Oncology Service, Madrid, Spain; Hospital Universitario de Canarias, Medical Oncology Service, Santa Cruz de Tenerife, Spain; Hospital Universitario Fundacion Jimenez Diaz, Medical Oncology Service, Madrid, Spain; Hospital Universitario San Cecilio, Medical Oncology Service, Granada, Spain; Hospital San Pedro de Alcantara, Medical Oncology Service, Caceres, Spain; Complexo Hospitalario Universitario de Vigo, Medical Oncology Service, Vigo, Spain; Hospital Universitario 12 de Octubre, Medical Oncology Service, Madrid, Spain; Hospital Universitari Vall d’Hebron, Medical Oncology Service, Barcelona, Spain; Hospital General Universitario de Alicante, Medical Oncology Service, Alicante, Spain; Hospital Universitario Lozano Blesa, Medical Oncology Service, Zaragoza, Spain; Hospital Universitario Quiron, Medical Oncology Service, Madrid, Spain; 17 Instituto Valenciano de Oncologia IVO, Medical Oncology Service, Valencia, Spain; Hospital Universitario Rio Hortega, Medical Oncology Service, Valladolid, Spain; Hospital Universitario de Salamanca, Medical Oncology Service, Salamanca, Spain; Hospital General Universitario de Ciudad Real, Medical Oncology Service, Ciudad Real, Spain

Aim: AXI is a vascular endothelial growth factor receptor tyrosin kinase inhibitor recently approved for the treatment of patients (pts) with RCC after failure of sunitinib or a cytokine. In a phase III study, AXI showed an improved progression free survival (PFS) compared to sorafenib after failure to one prior treatment. Methods: A retrospective data collection of pts treated under the Spanish compassionate use program was carried out. The objective of the study was to analyze the efficacy and safety of AXI in the real life setting. The study was approved by the regulatory authorities. Results: From September 2011 to March 2014, a total of 225 pts from 45 centers were included, 73.3% were male and the median age was 55 years (range 29-86). 80% had clear cell RCC and 88.4% had prior nephrectomy. 47.6% received AXI in 2nd line, 29.8% in 3rd line and 24.7% in 4th or subsequent line. The starting dose was 5 mg/12h in 97.3% of pts, 13.1% had at least one dose titration and 16.4% a dose reduction, mainly due to toxicity. At present, 30.8% of the pts continue on treatment with AXI. The response rate (RR) was 24% with 41.5% of disease stabilization (SD). Median PFS for all pts was 4.86 months (95%CI 3.92-5.81). Median PFS for pts that received AXI in 2nd, 3rd, or 4th or further line was 3.45, 5.03 and 5.49 months respectively (p= 0.383). Patients that achieved a response had a longer PFS than those who achieved only SD with a PFS of 12.32 and 7.00 months respectively (p = 0.009). PFS was also analyzed for several patient subgroups: Patient subgroup PFS (months) p value Clear cell vs. non-clear cell 4.93 vs. 3.88 0.098 Prior nephrectomy vs. no nephrectomy 5.03 vs. 2.69 0.106 Age 5.03 vs. 3.45 0.322 PS 0-1 vs. PS ≥2 5.68 vs. 2.56 No or mild renal impairment vs. moderate or severe renal impairment 4.60 vs. 4.90 0.484 Median overall survival (OS) for all pts was 9.63 months. 76.9% of pts developed at least one adverse event (AE). Most common AE were, all grades (grade 3-4): asthenia 52% (9.3%), diarrhea 30.6%(4.8%) and hypertension 30.1% (2.2%). Conclusions: The overall PFS is similar to the one reported in the phase III trial in patients previously treated with sunitinib. These data confirm the efficacy and safety of AXI in an unselected population. Disclosure: All authors have declared no conflicts of interest.

Aim: Heredofamilial cancer syndromes (HCS) need a multidisciplinary approach, since: 1) different organs and systems can be affected; and 2) different risk-reducing strategies, involving several medical and surgical specialists, should be provided. With this in mind, we implemented in 2010 a multidisciplinary heredofamilial cancer unit (HFCU) in our hospital. Methods: Retrospective analysis of the first 4 years the HFCUs activity. Results: A total of 1070 patients, from 927 different families were attended. 761 (71%) patients fulfilled international criteria for HCS. Genetic test results (GTR) were available for 323 patients at the time of analysis, with 115 cases (35.6%) of pathological mutations (MUT) detected. New mutation detection rate (first time diagnosis in a family) was 22%.The distribution according to pathology is summarized in the table. In patients with pathogenic mutations, risk reducing surgery (RRS) and /or follow up were offered according to international guidelines and patients' preferences: 34.8% patients went to RRS, while 65.2% only went to follow up. MUT / GTR (%) Breast & ovarian 84/231 (36.3) Lynch 14/36 (38.9) Poliposis 6/16 (37.5) Li Fraumeni 2/10 (20) Melanoma/pancreas 1/8 (12.5) Cowden 1/7 (14.3) MEN 3/6 (50) VHL 1/3 (33.3) Diffuse gastric 1/3 (33.3) NF1 1/2 (50) Gorlin 1/1 (100) TOTAL 115/323 (35.6) Conclusions: The implementation of an HFCU has provided a multidisciplinary assistance to a wide number of patients at risk in its first four years of activity. Patients were well pre-selected, as revealed by the high new mutation detection rate. However, further analysis must be done in order to evaluate the real impact of these interventions, to improve the different steps and timing of the genetic counseling process, and to receive the input from patients and their families Disclosure: All authors have declared no conflicts of interest.

Aim: We previously reported results from AGO-OVAR16 (NCT00866697), a randomized, double-blind, placebo-controlled phase 3 trial that evaluated the efficacy, safety, and tolerability of pazopanib maintenance therapy in patients without disease progression after first-line chemotherapy for AEOC (du Bois et al, ASCO 2013; abstract LBA5503). Patients in the pazopanib arm had longer progression-free survival (PFS) versus those in the placebo arm (HR = 0.766; 95% CI: 0.643, 0.911; P = .0021; medians 17.9 vs 12.3 months, respectively). The first interim analysis for overall survival (OS) after 190 deaths (20% of the study population) revealed no difference between arms (HR = 0.994; 95% CI: 0.747, 1.321). In this report we present updated results from the planned second interim OS analysis after 335 events (36% of the study population; 61% of events required for the final OS analysis, which will be performed after 551 events). Methods: Eligible patients had histologically confirmed AEOC, FIGO stage II-IV, and no evidence of disease progression after surgery and ≥ 5 cycles of platinum-taxane chemotherapy. Patients were randomized 1:1 to receive pazopanib 800 mg once daily or placebo for up to 24 months. The primary endpoint was PFS by RECIST. Secondary endpoints included OS, safety, and quality of life. Results: A total of 940 patients were randomized. At this second interim analysis of OS, 172 patients (36%) in the pazopanib arm and 163 patients (35%) in the placebo arm had died (HR = 1.076; 95% CI: 0.868, 1.333; P = .4985). The majority of deaths in each arm were attributed to the cancer under study. Additional subgroup analyses are ongoing and will be presented. Conclusions: Results from this updated OS analysis are consistent with the first interim analysis. Although maintenance therapy with pazopanib in AEOC significantly prolonged PFS in the overall study population, no difference in OS was observed in the planned second interim OS analysis. Disclosure: J.A. Arranz Arija: I have received honorarium for participating in advisory boards organized by GSK. I have received honorarium for participating as speaker in meetings organized by GSK. I do not have other economic relationships nor interest with GSK; N. Colombo: I have to declare participation in advisory boards; B.J. Monk: I have received honoraria for Advisory Boards. GSK supports research done at my institution and the payments do not go to me; T. Herzog: Consultant via advisory boards: Az, Roche, merk, morphotek No other as no speaker bureaus stock etc; C. Barrett and M. Jobanputra: I am employed by GlaxoSmithKline and hold GSK stock; Q. Wang: I'm a GSK employee and own GSK stocks. I do not have anything else to disclose; A. Du Bois: Consultant/advisor for Roche, Pharmamar, Amgen, and MSD Honoraria received from Roche, Johnson & Johnson, Pharmamar and MSD. All other authors have declared no conflicts of interest.

Aim: Cabazitaxel (C), a novel taxane developed to overcome docetaxel (D) resistance, showed an overall survival improvement after D in mCRPC in a three-weekly dose schedule. We aimed to evaluate efficacy and safety of a weekly C/prednisone (P) schedule in "unfit" mCRPC patients previously treated with D. Methods: Unfit pts (ECOG 2, dose reduction due to febrile neutropenia during treatment with D or radiation therapy affecting more than 25% of bone marrow reserve) with mCRPC progressing after D treatment with adequate bone marrow, liver and kidney functions were included. C 10 mg/m2 was administered on days 1, 8, 15 and 22 of 5-week cycles with P (5 mg b.i.d.). Radiological and PSA responses were evaluated according to the PCWG2 (Scher H, 2008) criteria and toxicity according NCI-CTC AE. Results: To date 69 pts have been enrolled and data are available for 54. Median age was 73 y (range 54-83); 59% pts had ECOG 2, 83% had bone, 19% liver and 9% lung metastases. 50% had Gleason > 7. Twenty three pts (43%) achieved ≥50% PSA response and 19 (35.2%) ≥80% PSA response. Response was evaluable in 28 pts. PR was observed in 1 pt (3.6%) and SD in 18 pts (64.3%). Median PSA PFS was 5.9 months. Median overall survival was 8.3 months. Most frequent toxicities of all grades as percentage of pts were: anemia (44.4%), asthenia (22.2%), thrombocytopenia (27.8%), leukopenia (18.5%), diarrhea (11.1%), nauseas (11.1%), neutropenia (5.6%), peripheral neuropathy (5.6%), and anorexia (3.7%). Grade 3-4: thrombocytopenia (20.4%), anemia (7.5%), leucopenia (3.8%), neutropenia (1.9%), asthenia (1.9%), diarrhea (1.9%), anorexia (1.9%), and peripheral neuropathy (1.9%). No grade IV diarrhea nor febrile neutropenia was observed. Conclusions: Administration of weekly C (10 mg/m2) plus P to unfit pts seems efficacious and safe with no grade 4 neutropenia, diarrhea or febrile neutropenia reported. Funding: Sanofi. 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.

Summary Purpose To evaluate the efficacy and toxicity of primary chemotherapy with the schedule E400P in the treatment of patients with early stage II (IIa and IIb) and advanced seminoma of good prognosis according to the international classification (IGCCCG) Patients and methods Sixty-four patients were included E400P consisted of cisplatin 25 mg/m2/day and etoposide 100 mg/m2/day for four days, every three weeks Royal Marsden stages were IIab 53% and IIc–IV. 47% Twenty-three percent had high BHCG levels, twenty-seven percent had LDH > 2 × N Sixty-two patients were of good prognosis according to the Medical Research Council classification Results Response rate was 98% (69% complete remission, 29% residual disease). After a median follow-up of 34 months, treatment failure was seen in 7 patients (11%) Neutropenia (32%) was the most relevant grade 3–4 toxicity Other important grade 3–4 side effects were found in less than 5% Three year time to treatment failure (TTF) was 89% (95% confidence intervals (CI) 80%–97%) for all patients, 91% (95% CI, 80%–99%) for stages IIa–b, and 87% (95% CI, 74%–99%) for stages IIc–IV Three-year overall survival (OS) was 97% (95% CI 93%–99%) for all patients and 95% (95% CI 85%–99%) for stages IIa–b Conclusions E400P was a very active and safe regimen in good-prognosis advanced seminoma, with low toxicity rates. Definitive comparisons of this regimen with radiotherapy in stages IIa–b or with the more standard E500P or BEP, could be of interest

Background Study results demonstrated that IFN augments BEV activity and improves median PFS in pts with mRCC. Thus, combination BEV + IFN is a standard first-line treatment option for mRCC. Combining BEV with the mTOR inhibitor EVE may be an efficacious and well-tolerated treatment option. The open-label, phase II RECORD-2 trial compared first-line EVE + BEV and IFN + BEV in mRCC. Patients and methods: Therapy-naive pts with clear cell mRCC and prior nephrectomy were randomized 1:1 to BEV 10 mg/kg IV every 2 weeks with either EVE 10 mg oral daily or IFN (9 MIU SC 3 times/week, if tolerated). Tumour assessments were every 12 weeks. Primary objective was treatment effect on progression-free survival (PFS) per central review based on an estimate of the chance of a subsequent phase III trial success (50% threshold for phase II success). Results In EVE + BEV (n = 182) and IFN + BEV (n = 183) arms, median age was 60/60 years, 76/72% of pts were men, MSKCC risk was favourable/intermediate/poor in 36/57/7% and 36/57/7% of pts, and 43/46% of pts had >2 organs involved, respectively. For EVE + BEV and IFN + BEV, median treatment duration was 8.5/8.3 months, respectively; 23/26% of pts discontinued due to AEs. In EVE + BEV and IFN + BEV arms, median PFS by central review was 9.3/10.0 months (HRIFN/EVE, 0.91; 95% CI, 0.69-1.19; P =0.485), respectively; probability of subsequent phase III success was 5.1%. Results of central and local PFS analysis were consistent. Objective response rate was 27/28% in EVE + BEV and IFN + BEV arms, respectively. Median overall survival (OS) was not reached in the EVE + BEV arm and was 25.9 months (95% CI: 21.1, 30.2) in the IFN + BEV arm. Most frequent AEs (%) were stomatitis (63), proteinuria (49), diarrhoea (39), hypertension (38), and epistaxis (35) in EVE + BEV arm and decreased appetite (45), fatigue (41), proteinuria (37), and pyrexia (35) in IFN + BEV arm. Conclusions In RECORD-2, PFS and tolerability were similar for first-line EVE + BEV and IFN + BEV. Final OS analysis will occur after 2-year follow-up. Disclosure A. Ravaud: Alain Ravaud is a member of global, European, and/or French boards on urological tumors for Pfizer, Novartis, GlaxoSmithKline, Bayer-Schering, and Dendreon, and has received institutional grant support from Pfizer, Novartis, and Roche. O. Anak: Ozlem Anak is an employee of Novartis Pharma AG. D. Pelov: Diana Pelov is an employee of Novartis Pharmaceuticals Corporation. A. Louveau: Anne-Laure Louveau is an employee of Novartis Pharma S.A.S. T. M-H: Tay M-H is a speaker for an advisory board for Novartis Pharmaceuticals Corporation. B. Melichar: Bohuslav Melichar has received honoraria from Novartis and Roche and served on an advisory board for Roche. All other authors have declared no conflicts of interest.

Background ACT for IBC is controversial and supported by underpowered randomized trials. Additional information from metanalysis or longitudinal studies can help to better define its role. Patients and methods From 1988 to 2011, patients (p) with IBC after C have been included in a risk-adapted institutional policy. After being informed of their particular risk of relapse, status of the art and toxicity of ACT, p with extravesical or N+ disease were recommended ACT although some of them chose follow-up. The opposite occurred with pT2N0 p. C and ACT cohorts were prospectively followed according to the standard clinical practice. ACT was associated with a reduction in the risk of relapse and death versus C, in patients with extravesical extension or N+ (JCO 29: 2011 suppl; abstr 4613). We present here the results of toxicity, progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS) comparing MVAC vs PG in the cohort of p who received ACT. Results 527 have been included, 331 C and 196 ACT: 90 MVAC x3, 90 CDDP-Gem x4, 16 Carbo-Gem x4 (106 PG). All PG were indicated after year 2000. Median follow-up was 86 m. MVAC vs PG were well balanced in sex (males 92% vs 86%), G3 (97% vs 96%), surgical complications (28% vs 26%), and %p who received full planned ACT (44% vs 52%). There were statistically significant differences in mean age (61 vs 67 y), non-papillary histology (71 vs 87%), and AJCC 2010 stage (T2N0/T3-4aN0/N + : 23%/30%/47% vs 10%/37%/53%). There were no toxic deaths. Main differences in G3-4 toxicities were anemia (11 vs 18%) neutropenia (42 vs 30%), trombopenia (5 vs 15%), emesis (12 vs 7%), and mucositis (8 vs 4%). There were no significant differences between MVAC and PG in crude PFS, OS or CSS. Table shows the Hazard Ratio (HR) of relapse and death stratified by pathological stage and adjusted by most relevant covariates in a multivariate Cox model (* p PFS CSS OS MVAC vs C Unadjusted 1.2 1.1 1 Multivariate pII Multivariate pIII Multivariate pIV 1 0.7 0.7 0.7 0.7 0.7 0.3 * 0.2 0.3 * PG vs C Unadjusted 1.4 1.1 1 Multivariate pII Multivariate pIII Multivariate pIV 2.2 2.7 2.3 0.4 * 0.4* 0.4 * 0.4 * 0.4* 0.3 * PG vs MVAC Unadjusted 1.1 1 1 Multivariate pII Multivariate pIII Multivariate pIV 1.6 1.6 1.7 0.7 0.8 0.9 1.2 0.9 0.8 Conclusion In our series of IBC, comparison of MVACx3 vs PGx4 as ACT showed some differences in toxicity, but we could not find significant differences in efficacy between both schedules. Disclosure All authors have declared no conflicts of interest.