Abstract BACKGROUND IDH mutant gliomas are brain tumors with a high impact in quality of life and morbidity in the AYA (young adults and adolescents) population. It is a very heterogeneous disease with different treatment options and a new effective targeted therapy (vorasidenib) very well tolerated. More RWD is needed to advance faster in the best management of this population. METHODS A retrospective cohort study of all IDH mutant gliomas diagnosed from 2019 to 2023 in 21 Spanish centers, a total of 485 cases. This study includes data from a GEINO questionnaire (21 centers) and from the RETSINE (Spanish registry of CNS tumors). GEINO questionnaire includes 2021 WHO diagnosis, treatment strategy decision and how many remain in watch and wait (WW) strategy in 2024. RESULTS From 2019 to 2023, 485 cases of IDH mutant glioma were diagnosed in 21 centers, 67% astrocytomas (A) (326/485) and 33% oligodendrogliomas (O) (159/485). WW strategy was relatively frequent in low grade gliomas (LGG) 33% (75/226), and slightly more frequent in O grade 2 40% (41/103) than in A grade 2 28% (34/123). WW strategy was decided in only 3% of grade (gr) 3 IDH mutant gliomas (5/172). Despite this, with a very short follow-up, 24% (19/80) of WW population have ended up receiving treatment, radiotherapy (RT) or chemotherapy (CT). We have collected all data from 241 cases in RETSINE. Median age was 46 years old and 56% were male. Nearly half were glioma grade 2, 46% (67 A, 45 O), 32% grade 3 (49 A, 28 O) and 21% grade 4 (52). Complete resection was achieved in 35%, Karnofksy index (KPS) was superior to 80% in 70% and neurologic deficit at diagnosis was present in 35%. Almost 50% had epileptic seizures at diagnosis. Overall survival (OS) at 2 years is 94% (O gr2), 96% (O gr3), 91% (A gr2), 82% (A gr3) and 55% (A gr4) and progression-free survival at 2 years is 80% (O gr2), 91% (O gr3), 74% (A gr2), 51% (A gr3) and 27% (A gr4), with a median follow up of 1,8 years. Univariate analyses for OS in astrocytomas confirm the prognostic role of various factors: histologic grade 3-4 (HR 4.07; 1.56-10.6; p=0.004), KPS >80% (HR 0.19; 0.09-0.42; p<0.001); tumor size ≥ 6 cm (HR 2.53; 1.1-5.85; p=0.03) and previous neurologic deficit (HR 2.64; 1.27-5.49; p=0.01). WW population was enriched with complete resection and younger age (<40 years old). All detailed data of almost 600 patients or more will be presented at the congress, more centers will be included in this project. CONCLUSIONS RWD of IDH mutant gliomas in Spain demonstrates that WW is a strategy decision in 33% of LGG, 40% in oligodendrogliomas grade 2. Despite this, in short follow-up, 24% of these end up receiving RT and/or CT. RWD can help to better understanding the disease and optimize patient care strategies in the new era of IDH inhibitors. We should work on better quality data on registries, including quality of life parameters as capacity for work in this long-term disease with a high impact on morbidity.

Recent advances in molecular profiling, have reclassified medulloblastoma, an undifferentiated tumor of the posterior fossa, in at least four diseases, each one with differences in prognosis, epidemiology and sensibility to different treatments. The recommended management of a lesion with radiological characteristics suggestive of MB includes maximum safe resection followed by a post-surgical MR < 48 h, LCR cytology and MR of the neuroaxis. Prognostic factors, such as presence of a residual tumor volume > 1.5 cm2, presence of micro- or macroscopic dissemination, and age > 3 years as well as pathological (presence of anaplastic or large cell features) and molecular findings (group, 4, 3 or p53 SHH mutated subgroup) determine the risk of relapse and should guide adjuvant management. Although there is evidence that both high-risk patients and to a lesser degree, standard-risk patients benefit from adjuvant craneoespinal radiation followed by consolidation chemotherapy, tolerability is a concern in adult patients, leading invariably to dose reductions. Treatment after relapse is to be considered palliative and inclusion on clinical trials, focusing on the molecular alterations that define each subgroup, should be encouraged. Selected patients can benefit from surgical rescue or targeted radiation or high-dose chemotherapy followed by autologous self-transplant. Even in patients that are cured by chemorradiation presence of significant sequelae is common and patients must undergo lifelong follow-up.

Ra223 is a life-prolonging alpha-emitter bone targeted therapy for mCRPC patients with bone metastases. However, evidence on biomarkers that may help us in patient selection are lacking. Total ALP (tALP) appeared to be a potential marker of Ra223 effect in early studies (Sartor, Ann Oncol, 2017). Other bone-related markers, as bone-specific ALP (BALP), have demonstrated its prognostic value in mCRPC patients with bone metastases (Fizazi K, Eur Urol, 2015; Lara PN, J Natl Cancer Inst, 2014).

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.

Abstract BACKGROUND Standard treatment of glioblastoma (GBM) is focal radiation with concomitant and adjuvant temozolomide (TMZ) for 6 cycles. The GEINO-14-01 trial (NCT02209948) investigated the role of extending adjuvant TMZ to 12 cycles in a randomized multicenter study. MATERIAL AND METHODS Between Aug/2014 and Nov/2018, 166 patients (p) were screened and 159 randomized to extend (80p) or not (79p) TMZ treatment to 12 cycles after proving stable disease in the MRI performed before inclusion. The trial was stratified by MGMT status and presence or absence of residual disease (defined as a residual enhancement larger than 1cm on the MRI). The primary endpoint was differences in 6monthsPFS, secondary endpoints were differences in PFS, OS, toxicity, between arms and per stratification factors. RESULTS Median age was 60.4 (range 29–83), 97p (61%) were methylated and 83 p (52.2%) were reported with residual disease. Median (m) PFS was 7.9 months (95%CI: 6.1–9.8) and mOS: 20.9 (95%CI: 17.6–24.1). A methylated status was a factor of better PFS (HR=0.29, 95% CI 0.46–0.95; p=0.029) and better OS (HR= 0.43: 95% CI 0.28–0.66; p=0.000) as well as the absence of residual disease (PFS: HR = 0.84: 95% CI =0.71–1.01; p=0.068; OS: HR=0.77, 95%CI 0.63–0.96; p=0.019). We didn’t find any difference in PFS (HR=1.02, 95%CI 0.85–1.21; p=0.82), or OS (HR=0.90; 0.73–1.11; p=0.34) on extending treatment with temozolomide longer than 6 cycles. CONCLUSION There is no benefit of continuing TMZ treatment for more than 6 cycles in the adjuvant treatment of glioblastoma. Final data will be presented at the congress. Supported by a Grant of the ISCIII: PI13/01751

Abstract Background Glioblastoma (GB) is the most common malignant CNS tumor. Incidence ingreases with age, peaking between 69 and 84 yers, and half of patients diagnosed have > 65 years. The question about how to treat these patients remains object of controversy. The purpose of this survey was to know the treatment recommendations for BG in academic Spanish hospitals. Methods In 2018, surveys were e-mailed to all members of GEINO (Spanish Group for Neurooncology Reseach). The survey contained specific questions on the routine clinical practice regarding treatment recommendations for elderly patients with GB and anaplastic astrocytoma in different clinical situations: depending on ECOG, morbility, MGMT promoter methylation, age intervals (between 65-70 y, 70-80 y, >80 y). Response options were: a) Stupp regimen, b) Perry regimen, c) Radiation or TMZ depending on MGMT status and d) supportive care. Participants were also asked if they used MGMT status to select patients for Stupp or Perry regimen. Results Twenty-six neuro-oncoligist from twenty-six hospitals completed the survey. Mean of hospital beds of the institutions were 833.19 (range 150-1500). Mean of hospital veds of the instituions were 833,19 (range 150-1500). Median number of new cases treated per year were 31 (range 8-80). In patients with ECOG 0-1 and between 65 and 70 years old, 80.8 % of participants would recommend treatment with Stupp regiment. For patients with ECOG 0-1 and between 70-80; 46.2 % recommenden Perry regimen in methylated (M) and unmethylated (UM) patients; 38.5 % recommended Stupp regimen in both. For with ECOG 0-1 and > 80 % yo, 46,2 % recommend Perry regimen in both M and UM; 3.8 % Stupp regimen; 15,4 % radiation or TMZ according to MGMT status. In patients with anaplastic astrocytoma aged 70-80 y, 46,2 % would recommend Perry regimen and 42,3 % Stupp regimen. Table: 411P . Most recommend treatment Percentage of responders Glioblastoma, age 70-80 (PS 0-1, minor comorbility) Perry Stupp 46.2 % 38.5 % Glioblastoma, age >80 (PS 0-1, mior comorbility Perry 46.2 % Glioblastoma, age 65-70 (PS 0-1, minor comorbility) Stupp 80.8 % Glioblastoma, no MGMT methylation 70-80 >80 65-70 Stupp Perry Stupp 50 % 34.6 % 68.5 % Glioblastoma >65, PS > 2 Stupp 36.8 % Anaplastic astrocytoma 70-80 yo Perry 30.8 % Anaplastic astrocytoma >80 Perry 34.6 % Anaplastic astrocytoma 65-70 Stupp 53.8 % Conclusions Our research demonstrates there is no uniform approach to the management of elderly patient with glioblastoma among academic neuro-oncologist. Legal entity responsible for the study GEINO (Grupo Espanol de Investigacion en Neurooncologia). Funding Has not received any funding. Disclosure M. Vaz Salgado: Advisory / Consultancy, Travel / Accommodation / Expenses: Pharmamar; Advisory / Consultancy: Lilly, Eisai y Celgene; Research grant / Funding (self): Pfizer. M. Vieito Villar: Travel / Accommodation / Expenses: Roche. R. Luque: Honoraria (self), Travel / Accommodation / Expenses: Janssen-Cilag; Honoraria (self), Travel / Accommodation / Expenses: Sanofi Aventis; Honoraria (self), Travel / Accommodation / Expenses: Astellas Medivation; Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Travel / Accommodation / Expenses: Bristol Mayers Squibb; Honoraria (self), Travel / Accommodation / Expenses: EUSA Pharma. 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.

PurposeWe retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients.Patients and methodsWe compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy.ResultsOS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13weeks for the NA group and 4.2weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12weeks and the shortest by patients who started radiotherapy within 4weeks (12.3 vs 6.6months) (P=0.05). OS was 6.6months for patients who started radiotherapy before the optimal cutoff of 6.43weeks and 19.1months for those who started after this time (P=0.005). Patients who completed radiotherapy had longer OS than those who did not, in all 215 patients and in the NA and NoNA groups (P=0.000). In several multivariate analyses, completing radiotherapy was a universally favorable prognostic factor, while neoadjuvant therapy was never identified as a negative prognostic factor.ConclusionIn our series of unresected patients receiving neoadjuvant treatment, in spite of the delay in starting radiotherapy, OS was not inferior to that of a similar group of patients with no delay in starting radiotherapy.

Glioblastoma (GB) is the most common brain malignancy and accounts for over 50% of all high-grade gliomas. Radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ) chemotherapy is the current standard of care for patients with newly diagnosed GB up to age 70. Recently, a new standard of care has been adopted for elderly patients (≥ 65 years) based on short course of RT and TMZ. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent GB is not well defined, and decision-making is usually based on prior strategies as well as several clinical and radiological factors. The presence of neurologic deficits and seizures can significantly impact quality of life.

We assessed agreement among neurosurgeons on surgical approaches to individual glioblastoma patients and between their approach and those recommended by the topographical staging system described by Shinoda.

BACKGROUND: RANO criteria were applied to evaluate differences in response between the 2 arms: TMZ or TMZ + BEV in a randomized study. We evaluate here the RANO sub-criterion (PI) to evaluate response. METHODS: Between December 2009 and April 2013, p with unresectable GBM, PS < 3 and MMS ≥25 were randomly assigned to receive eitherTMZ (200 mg/m2, days 1–5,for 2 28-day cycles), followed by standard TMZ with concomitant radiotherapy (60Gy) and then adjuvant TMZ for 6 cycles (TMZ Arm), or the same regimen but with the addition of BEV (10mg/kg /15 days) during pre-radiotherapy and concomitant treatment (BEV Arm). The primary endpoint was response according to RANO criteria after the 2 pre-radiotherapy cycles. The study was powered to detect a 30% difference between arms. A centralized revision of MRI's blinded to clinical status of p is ongoing. (ClinicalTrials.gov NCT01102595). RESULTS:103 p were registered and 93 randomized – 45 to the TMZ Arm and 48 to the BEV Arm. All p who received at least one dose of treatment were included in the analysis. Overall response rate (ORR) was evaluated after the 2-pre-radiotherapy cycles. Patients completed pre-radiotherapy treatment in 48.9% (TMZ Arm) vs 66.7% (BEV Arm), p = 0.08. Response was not evaluable in 3p (TMZ arm) and 5p (BEV arm) because of previous toxicity or refuse to continue. ORR by RANO criteria for evaluable p was: Arm TMZ: PR 3 (7.1%) SD 8 (19%) PD 31 (73.8%)., Arm B: PR 11 (25.6%) SD 17 (39.5%) 15 (34.9%) P = 0.001. Response by individual RANO sub criterion (Arm TMZ% vs Arm BEV%).1- MRI IP: PR (8.3 vs 26.2), SD (22.2 vs 42.8), P (69.4 vs 31) (P = 0.003), 2-Neurological status: SD (54.8 vs 79.5), No SD (45.2 vs 20.5) (P = 0.014), 3-Dexametasone dose: stable (60.5 vs 51.2), increase (28.9 vs 4.7), reduction (10.5 vs 44.2) (P < 0.001). CONCLUSION: ORR was significantly higher in the BEV Arm for both for general RANO criteria as for each individual criterion (MRI, clinical stability and dexametasone doses.

I. Duran1, C. Hagen2, J.A. Arranz Arija3, M. Apellaniz4, B. Pérez-Valderrama1, N. Sala Gonzalez5, N. Lainez6, X. Garcia Del Muro7, E. Nogueron8, M. Climent9, P. Maroto10, A. Font11, J. Garcia-Donas12, E. Gallardo13, P. Lopez Criado14, A. Gonzalez Del Alba15, M.I. Saez16, S. Vazquez17, R. Luque18, C. Rodriguez-Antona4 Departamento de Oncologia, Hospital Universitario Virgen del Rocio, Seville, SPAIN Translational Research, Spanish Oncology Genitourinary Group, Madrid, SPAIN Servicio de Oncologia Medica, Hospital General Univ. Gregorio Marañon, Madrid, SPAIN Human Genetic, Spanish National Cancer Research Center, Madrid, SPAIN Medical Oncology, ICO Josep Trueta, Girona, SPAIN Medical Oncology, Complejo Hospitalario de Navarra, Pamplona, SPAIN Medical Oncology, Institut Catal, L’Hospitalet de Llobregat, SPAIN Dept. of Medical Oncology, Complejo Hospitalario Universitario de Albacete, Albacete, SPAIN Medical Oncology, Instituto Valenciano de Oncologia, Valencia, SPAIN Dept. of Medical Oncology, Hospital de la Sta. Creu i St. Pau, Barcelona, SPAIN Medical Oncology, Catalan Institute of Oncology ICO Badalona Hospital Germans Trias i Pujol, Medical Oncology, Badalona, SPAIN Madrid, Hospital Madrid Norte San Chinarro Centro Integral Oncologico Clara Campal, Madrid, SPAIN Oncologia Medica, Hospital de Sabadell Corporacis Parc Tauli, Sabadell, SPAIN Medical Oncology, MD Anderson Madrid, Madrid, SPAIN Medical Oncology, Hospital Universitario Son Espases, Palma de Mallorca, SPAIN Medical Oncology, Hospital Universitario Virgen de la Victoria, Malaga, SPAIN Oncoloxia Médica, Hospital Universitario Lucus Augusti de Lugo, Lugo, SPAIN Medical Oncology Unit, Hospital Universitario Virgen de las Nieves, Granada, SPAIN

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.

Aim: We compared treatment with TMZ versus TMZ + BEV prior to and concomitant with radiotherapy in unresectable GBM p. The potential prognostic role of MGMT methylation was examined in p with available tissue and/or serum samples.

Background: Based on the TROPIC study results, cabazitaxel was approved for the management of metastatic castration-resistant prostate cancer (mCRPC) progressing on or after docetaxel. Methods: This multi-centre program provided early access to cabazitaxel to patients with mCRPC before its commercialization. Safety data from 153 Spanish patients receiving cabazitaxel 25 mg/m2 i.v. Q3W, plus oral prednisone/prednisolone 10 mg daily, are reported. Results: Median age of patients was 70 years (26.8% ≥ 75 years), 94.1 and 26.8% had bone and visceral metastasis, respectively. Most had an Eastern Cooperative Oncology Group ≤ 1 (88.9%) and had received a median of 8.0 cycles of last docetaxel treatment. The median of cabazitaxel cycles and cumulative dose were 6.0 (Interquartile range [IQR]: 4.0; 8.0) and 148.9 (IQR: 98.2; 201.4) mg/m2, respectively. Adverse events (AEs) possibly related to cabazitaxel occurred in 143 (93.5%) patients. The most frequent grade ≥ 3 AEs were neutropenia (n = 25, 16.3%) and asthenia (n = 17, 11.1%). Febrile neutropenia and grade ≥ 3 diarrhea occurred in 5.2% of the patients each. There were five (3.3%) possibly treatment-related deaths, mainly infection-related. G-CSFs were used in 114 (74.5%) patients, generally as prophylaxis (n = 107; 69.9%). Grade ≥ 3 peripheral neuropathy and nail disorders were uncommon. Conclusions: Cabazitaxel administration, in a real-world setting, is tolerated by Spanish patients with mCRPC, and the AEs are manageable.