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Background : Axitinib monotherapy obtained approval in pre-treated metastatic renal cell carcinoma (mRCC) patients and recently in combination with pembrolizumab or avelumab in the first-line setting. However, patient profiles that may obtain increased benefit from this drug and its combinations still need to be identified. Patients and Methods : Retrospective multicentre analysis describing clinical characteristics associated with axitinib long-responder (LR) population by comparing two extreme-response sub-groups (progression-free survival [PFS] ≥9 months versus disease progression/refractory patients [RP]). A multivariate logistic-regression model was used to analyse clinical factors. Efficacy and safety were also analysed. Results : In total, 157 patients who received axitinib in second or subsequent line were evaluated (91 LR and 66 RP). Older age at start of axitinib and haemoglobin levels > LLN were independent predictive factors for LR in multivariate analyses. In LR patients, median (m) PFS was 18.1 months, median overall survival (OS) was 36.0 months and objective response rate (ORR) was 45.5%. In 59 LR patients receiving axitinib in second-line, mPFS was 18.7 months, mOS was 44.8 months and ORR was 43.9%. mOS was significantly longer in second line compared to subsequent lines (44.8 versus 26.5 months; P=0.009). In LR versus RP, mPFS with sunitinib in first-line was correlated with mPFS with axitinib in second-line (27.2 versus 10.9 months P Conclusions : This study confirms the long-term benefits of axitinib in a selected population, helping clinicians to select the best sequential approach and patients who could obtain a greater benefit from axitinib. Microabstract Patients with metastatic renal cell carcinoma (mRCC) who may benefit most from axitinib still need to be identified. AXILONG study confirms long-term benefits in a selected population in which age at axitinib initiation and haemoglobin baseline levels were significantly associated although further validation may be required. First-line sunitinib outcomes were also correlated with prolonged response. These results might be helpful in real-life management of mRCC patients.

[EN] Purpose: To systematically review evidence regarding the association of multi-parametric biomarkers with clinical outcomes and their capacity to explain relevant subcompartments of gliomas. Materials and Methods: Scopus database was searched for original journal papers from January 1st, 2007 to February 20th , 2017 according to PRISMA. Four hundred forty-nine abstracts of papers were reviewed and scored independently by two out of six authors. Based on those papers we analyzed associations between biomarkers, subcompartments within the tumor lesion, and clinical outcomes. From all the articles analyzed, the twenty-seven papers with the highest scores were highlighted to represent the evidence about MR imaging biomarkers associated with clinical outcomes. Similarly, eighteen studies defining subcompartments within the tumor region were also highlighted to represent the evidence of MR imaging biomarkers. Their reports were critically appraised according to the QUADAS-2 criteria. Results: It has been demonstrated that multi-parametric biomarkers are prepared for surrogating diagnosis, grading, segmentation, overall survival, progression-free survival, recurrence, molecular profiling and response to treatment in gliomas. Quantifications and radiomics features obtained from morphological exams (T1, T2, FLAIR, T1c), PWI (including DSC and DCE), diffusion (DWI, DTI) and chemical shift imaging (CSI) are the preferred MR biomarkers associated to clinical outcomes. Subcompartments relative to the peritumoral region, invasion, infiltration, proliferation, mass effect and pseudo flush, relapse compartments, gross tumor volumes, and high-risk regions have been defined to characterize the heterogeneity. For the majority of pairwise cooccurrences, we found no evidence to assert that observed co-occurrences were significantly different from their expected co-occurrences (Binomial test with False Discovery Rate correction, alpha=0.05). The co-occurrence among terms in the studied papers was found to be driven by their individual prevalence and trends in the literature. Conclusion: Combinations of MR imaging biomarkers from morphological, PWI, DWI and CSI exams have demonstrated their capability to predict clinical outcomes in different management moments of gliomas. Whereas morphologic-derived compartments have been mostly studied during the last ten years, new multi-parametric MRI approaches have also been proposed to discover specific subcompartments of the tumors. MR biomarkers from those subcompartments show the local behavior within the heterogeneous tumor and may quantify the prognosis and response to treatment of gliomas., This work was supported by the Spanish Ministry for Investigation, Development and Innovation project with identification number DPI2016-80054-R.

Objective: To assess whether the treatment with intermittent pneumatic compression plus multilayer bandages is not inferior to classical trimodal therapy with manual lymphatic drainage in the decongestive lymphedema treatment. Study Design: Randomized, non-inferiority, controlled study to compare the efficacy of three physical therapies’ regimens in the Decongestive Lymphatic Therapy. Participants: 194 lymphedema patients, stage II–III with excess volume > 10% were stratified within upper and lower limb and then randomized to one of the three treatment groups. Baseline characteristics were comparable between the groups. Intervention: all patients were prescribed 20 sessions of the following regimens: Group A (control group): manual lymphatic drainage + Intermittent Pneumatic Compression + Bandages; Group B: pneumatic lymphatic drainage + Intermittent Pneumatic Compression + Bandages; and Group C: only Intermittent Pneumatic Compression + Bandages. End-point: Percentage reduction in excess volume (PREV). Results: All patients improved after treatment. Global mean of PREV was 63.9%, without significant differences between the groups. The lower confidence interval of the mean difference in PREV between group B and group A, and between group C and group A were below 15%, thus meeting the non-inferiority criterion. Most frequent adverse events were discomfort and lymphangitis, without differences between groups. A greater baseline edema, an upper-limb lymphedema and a history of dermatolymphangitis were independent predictive factors of worse response in the multivariate analysis. Conclusions: Decongestive lymphatic therapy performed only with intermittent pneumatic compression plus bandages is not inferior to the traditional trimodal therapy with manual lymphatic drainage. This approach did not increase adverse events.

Background Standard treatment for glioblastoma is radiation with concomitant and adjuvant temozolomide for 6 cycles, although the optimal number of cycles of adjuvant temozolomide has long been a subject of debate. We performed a phase II randomized trial investigating whether extending adjuvant temozolomide for more than 6 cycles improved outcome. Methods Glioblastoma patients treated at 20 Spanish hospitals who had not progressed after 6 cycles of adjuvant temozolomide were centrally randomized to stop (control arm) or continue (experimental arm) temozolomide up to a total of 12 cycles at the same doses they were receiving in cycle 6. Patients were stratified by MGMT methylation and measurable disease. The primary endpoint was differences in 6-month progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS), and safety (Clinicaltrials.gov NCT02209948). Results From August 2014 to November 2018, 166 patients were screened, 7 of whom were ineligible. Seventy-nine patients were included in the stop arm and 80 in the experimental arm. All patients were included in the analyses of outcomes and of safety. There were no differences in 6-month PFS (control 55.7%; experimental 61.3%), PFS, or OS between arms. MGMT methylation and absence of measurable disease were independent factors of better outcome. Patients in the experimental arm had more lymphopenia (P Conclusions Continuing temozolomide after 6 adjuvant cycles is associated with greater toxicity but confers no additional benefit in 6-month PFS. Key Points 1. Extending adjuvant temozolomide to 12 cycles did not improve 6-month PFS. 2. Extending adjuvant temozolomide did not improve PFS or OS in any patient subset. 3. Extending adjuvant temozolomide was linked to increased toxicities.

Background Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by a heterogeneous and abnormal vascularity. Subtypes of vascular habitats within the tumor and edema can be distinguished: high angiogenic tumor (HAT), low angiogenic tumor (LAT), infiltrated peripheral edema (IPE), and vasogenic peripheral edema (VPE). Purpose To validate the association between hemodynamic markers from vascular habitats and overall survival (OS) in glioblastoma patients, considering the intercenter variability of acquisition protocols. Study Type Multicenter retrospective study. Population In all, 184 glioblastoma patients from seven European centers participating in the NCT03439332 clinical study. Field Strength/Sequence 1.5T (for 54 patients) or 3.0T (for 130 patients). Pregadolinium and postgadolinium-based contrast agent-enhanced T1-weighted MRI, T2- and FLAIR T2-weighted, and dynamic susceptibility contrast (DSC) T2* perfusion. Assessment We analyzed preoperative MRIs to establish the association between the maximum relative cerebral blood volume (rCBVmax) at each habitat with OS. Moreover, the stratification capabilities of the markers to divide patients into 'vascular' groups were tested. The variability in the markers between individual centers was also assessed. Statistical Tests Uniparametric Cox regression; Kaplan–Meier test; Mann–Whitney test. Results The rCBVmax derived from the HAT, LAT, and IPE habitats were significantly associated with patient OS (P < 0.05; hazard ratio [HR]: 1.05, 1.11, 1.28, respectively). Moreover, these markers can stratify patients into 'moderate-' and 'high-vascular' groups (P < 0.05). The Mann–Whitney test did not find significant differences among most of the centers in markers (HAT: P = 0.02–0.685; LAT: P = 0.010–0.769; IPE: P = 0.093–0.939; VPE: P = 0.016–1.000). Data Conclusion The rCBVmax calculated in HAT, LAT, and IPE habitats have been validated as clinically relevant prognostic biomarkers for glioblastoma patients in the pretreatment stage. This study demonstrates the robustness of the hemodynamic tissue signature (HTS) habitats to assess the GBM vascular heterogeneity and their association with patient prognosis independently of intercenter variability. Level of Evidence: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1478–1486.

[Background]: The cell cycle checkpoint G1/S, dependent on cyclin-dependent kinase (CDK) 4 amplification/overexpression and retinoblastoma phosphorylation, is altered in most anaplastic oligodendrogliomas (AOs). [Objective]: We aimed to evaluate the efficacy of palbociclib, an oral inhibitor of CDK4/6 with proven efficacy in breast cancer, in patients with AO. The primary endpoint was progression-free survival at 6 months. [Patients and Methods]: We conducted a multicenter, open-label, phase II trial evaluating the efficacy and safety of palbociclib in patients with AO who progressed on radiotherapy and chemotherapy with histologically and molecularly confirmed grade 3 oligodendroglioma and conserved retinoblastoma protein (pRb) expression by immunohistochemistry. Patients were treated with palbociclib (125 mg/day) for 3/1 weeks on/off. [Results]: Overall, 34 patients were enrolled across 10 hospitals in the Spanish Group of Neuro-Oncology (GEINO) study. The study was stopped early owing to the lack of efficacy, with 74% of evaluable patients progressing within 6 months, which was insufficient to consider palbociclib as an active drug in this population. Within the median follow-up of 12 months, the median progression-free survival was 2.8 months [95% confidence interval (CI) 2.6–3.1] and the median overall survival was 32.1 months (95% CI 5.1–59.2). There were no partial or complete responses; only 13 patients (38%) achieved stable disease as the best response. Palbociclib was well tolerated, with neutropenia (grade 3 or higher: 58.8%) and thrombocytopenia (grade 3 or higher: 14.7%) as the most common adverse events (AEs). Both AEs had no significant impact. [Conclusion]: Despite the good tolerance, palbociclib monotherapy did not show favorable efficacy against recurrent AO., Palbociclib was provided by Pfizer under a cooperative research agreement with the Spanish Group for Research in NeuroOncology (GEINO). Funding research was supported by Pfzer under the Investigator-Initiated Research Award, number WI174842.

Background: The ever-growing complexity of cancer-associated thrombosis (CAT), with new antineoplastic drugs and anticoagulants, distinctive characteristics, and decisions with low levels of evidence, justifies this registry. Method: TESEO is a prospective registry promoted by the Spanish Society of Medical Oncology to which 34 centers contribute cases. It seeks to provide an epidemiological description of CAT in Spain. Results: Participants (N=939) with CAT diagnosed between July 2018 and December 2019 were recruited. Most subjects had advanced colon (21.4%), non-small cell lung (19.2%), and breast (11.1%) cancers, treated with dual-agent chemotherapy (28.4%), monochemotherapy (14.4%), or immune checkpoint inhibitors (3.6%). Half (51%) were unsuspected events, albeit only 57.1% were truly asymptomatic. Pulmonary embolism (PE) was recorded in 571 (58.3%); in 120/571 (21.0%), there was a concurrent deep venous thromboembolism (VTE). Most initially received low molecular weight heparin (89.7%). Suspected and unsuspected VTE had an OS rate of 9.9 (95% CI, 7.3-non-computable) and 14.4 months (95% CI, 12.6-non-computable) (p=0.00038). Six-month survival was 80.9%, 55.9%, and 55.5% for unsuspected PE, unsuspected PE admitted for another reason, and suspected PE, respectively (p

A systematic review was conducted to identify real world studies reporting outcomes after first-line pazopanib in patients with metastatic renal cell carcinoma. Studies had to be observational and report survival data in terms of progression-free survival and overall survival in order to conduct meta-analysis techniques. These real-world data were compared to those obtained in the phase II and III randomized controlled trials of pazopanib. Real world evidence showed that the clinical and safety outcomes were consistent with those observed in the clinical trials despite the inclusion of unselected patients with a wide spectrum of prognostic features and comorbidities. Similarly to the results of the pivotal studies, good prognosis patients had the most benefit from pazopanib. Further investigation is needed to complement evidence from clinical trials, in particular focused on patient-centered outcomes.

Càncer de bufeta; Cistectomia; Quimioteràpia Cáncer de vejiga; Cistectomía; Quimioterapia Bladder cancer; Cystectomy; Chemotherapy The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical–pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin–gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents.

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. 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 lack of progression of the 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), all p had ECOG≤1 and 86.2% were without DXM treatment. MGMT status: Met: 97 (61%) UnMet:62 (39%). RD yes: 83 (52.2%) and no: 76 (47.8%). At the time of the abstract report 3 patients are still on treatment or control without a documented progression and 5 patients have not been yet 6m in the study: 31 patients (19.5) are still free of progression and 60 patients (37.7%) are still alive. Median (m) PFS has been reached: 7.9 months (95%CI: 6.1-9.8) as well as 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. Toxicity data and final results are expected for the congress. Conclusions There is no benefit of continuing TMZ treatment for more than 6 cycles in the adjuvant treatment of glioblastoma. Met status and absence of RD are factors of better SLP after adjuvant treatment. Supported by a Grant of the ISCIII: PI13/01751. Clinical trial identification NCT02209948. Legal entity responsible for the study GEINO (Grupo Espanol de Investigacion en Neurooncologia). Funding Supported by a Grant of the ISCIII. Disclosure M.A.V. Salgado: Advisory / Consultancy: Lilly; Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: pharmamar; Advisory / Consultancy: eisai; Advisory / Consultancy: Celgene. All other authors have declared no conflicts of interest.

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

We report preliminarily results of an international retrospective study (NCT03439332) analyzing the prognostic value of the early assessment of vascular architecture of glioblastoma (GBM). The initial cohort included 300 pts treated at 7 European hospitals. Multiparametric images were processed by Oncohabitats (www.oncohabitats.upv.es) to obtain the cerebral blood volume (CBV) and cerebral blood flow (CBF) from 4 automatically delimited regions of interest (ROIs): high angiogenic tumor (HAT), low angiogenic tumor (LAT), infiltrating peripherial edema (IPE), and vasogenic peripherial edema (VPE). Uniparametric Cox regression models and Kaplan-Meier analysis were developed to test prognostic and stratification capabilities of each biomarker. 115 pre-surgical MRIs passed quality controls and were included in the analysis. Median follow up was 12.9 months (m) (IQR: 9.2-17.6). 73 pts (63.5%) were male. 54 pts (47%) underwent total resection; 84 pts (73%) received adjuvant temozolomide. Median OS was 13.6 m (95%CI:12.1-15.2). Cox regression analysis yielded a significant correlation between OS and maximum rCBV and rCBF in HAT and LAT (Table), independent of the extent of resection. Median OS by Kaplan-Meier analysis in patients with high and low vascularity is shown in the Table. Our preliminarily results shows that patients with lower vascularity (rCBV or rCBF) in vascular habitats inside enhancing tumor region (HAT and LAT) is associated with higher OS, and could improve patient stratification. Our results are consistent with our pilot study [1], Validation in large multicentric studies is underway. COX REGRESSION ANALYSISKAPLAN-MEIER STRATIFICATION ANALYSISCOX REGRESSION ANALYSISKAPLAN-MEIER STRATIFICATION ANALYSISHAZARD RATIO95% CONFIDENCE INTERVALP-VALUE*NUMBER OF PATIENTSMEDIAN SURVIVAL (months)P-VALUErCBV máximumHigh Angiogenic Tumor10.339[1.09- 1.14]0.0202*[29 86][16.66 12.78]0.004***Low Angiogenic Tumor10.485[1.17- 1.31]0.0262*[29 86][17.10 12.78]0.002***Infiltrating Peripheral Edema0.9835[1.30- 1.71]0.1208[29 86][14.60 12.91]0.119Vasogenic Peripheral Edema0.7942[1.14- 1.63]0.6046[29 86][15.23 12.91]0.220rCBF máximumHigh Angiogenic Tumor0.9997[1.02- 1.03]0.1077[47 68][14.93 11.65]0.009**Low Angiogenic Tumor10.411[1.21- 1.40]0.0384*[29 86][15.56 12.75]0.016*InfiltratingPeripheral Edema0.8923[1.35- 2.04]0.2589[29 86][15.23 12.83]0.394Vasogenic Peripheral Edema0.6846[1.11- 1.81]0.7447[29 86][14.60 12.96]0.508Table: Results of Cox-regression and Kaplan-Meier analysis. (P VALUE*: False discovery rate corrected.)[1]: https://doi.org/10.1148/radiol.2017170845 Citation Format: María del Mar Álvarez-Torres, Fuensanta Bellvís–Bataller, Javier Juan–Albarracín, Elies Fuster–Garcia, David Lorente Estellés, Gaspar Reynes, Fernando Aparici-Robles, Carlos Botella, Jose Muñoz-Langa, Raquel Faubel, Sabina Asensio-Cuesta, Germán Adrían García–Ferrando, Cristina Auger, Alex Rovira, Jose Pineda, Jaime Font de Mora, Enrique Mollà-Olmos, Antonio José Revert-Ventura, Luaba Tshibanda, Didier Martin, Girolamo Crisi, Kyrre Eeg Emblem, Paulina Due-Tonnessen, Torstein R Meling, Juan M García-Gómez. Preliminarily results of the Oncohabitats Study: A multicentre validation of overall survival (OS) estimation of patients with glioblastoma (GBM) using vascular biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4258.

2038 Background: The pRB-dependent cell cycle checkpoint is altered in the vast majority of anaplastic oligodendrogliomas (AO), either by homozygous deletion or by hypermethylation of CDKN2A and/or CDKN2B, or by amplification and/or overexpression of CDK4. Palbociclib is an oral inhibitor of CDK4 and 6 that has already been shown to be highly active in breast cancer. Methods: We conducted a multicenter, open-label, phase II trial evaluating efficacy and safety of Palbociclib in patients with AO that progressed to radiotherapy and more than one chemotherapy regimen containing Temozolomide and/or Lomustine. Inclusion criteria included: histologically and molecularly confirmed grade III oligodendroglioma (WHO 2016 classification, IDH1/2 mutation and 1p/19 codeletion were mandatory), recurrence after radiotherapy and 1 or 2 chemotherapy regimens and conserved RB protein expression by immunohistochemistry (IHC). Patients were treated with Palbociclib 125 mg/daily 3 weeks on/1off. The primary objective of the study was progression-free survival at 6 months (6M-PFS). Results: Between October 2015 and September 2018, 34 patients were enrolled across ten hospitals. The study was stopped early secondary to lack of efficacy, with 74% of evaluable patients progressing within 6 months. Number of patients alive and free from progression at 6 months after the enrollment was 9 (26%) out of the first 34 patients, below the minimum number required (18 out of 40) to consider Palbociclib as an active drug in this population. With a median follow-up of 11.2 months, the median PFS was 3 months (95% CI: 2.5-3.5 months). Median overall survival (OS) was 23.1 months (95% CI: 17.2-25 months). There were no partial or complete responses and only 11 patients (32%) achieved stable disease as best response. Palbociclib was well tolerated with neutropenia (Grade 3 or 4: 40%) and thrombocytopenia (Grade 3 or 4: 15%) as the most common adverse effects (AEs). Both AEs had no significant impact since there were no episodes of febrile neutropenia or bleeding. Conclusions: Despite the good tolerance and drug exposure, Palbociclib monotherapy did not show favorable activity in recurrent AO. Clinical trial information: NCT02530320.

2001 Background: The GEINO-14-01 trial (NCT02209948) investigated the role of extending temozolomide (TMZ) for 6 cycles after the standard 6 cycles to improve 6m-PFS, SLP and OS in newly diagnosed glioblastoma (GBM) patients (p). Methods: Between 08/2014 and 11/2018, 166 p were screened and 159 randomized to extend (80p) or not (79p) TMZ treatment for 6 cycles after proving stable disease in the MRI performed before inclusion. Centralized review of histology and determination of MGMT status, if not previously available, were performed before randomizing patients. Two criteria of stratification were used: MGMT status and presence/absence of residual disease on the basal MRI (defined as a residual enhancement larger than 1cm in one). The primary endpoint was differences in 6mPFS, secondary endpoints were differences in PFS, OS, toxicity, between arms and per stratification factors. Results: Median age was 60.3 (range 29-83), 97p (61%) were methylated, basal MRI showed residual disease in 57p (35.8%). After a median follow up of 14.0 months, with 121 p(76.1%) already progressed and 81p (50.9%) already dead, median PFS is presented. Median (m) PFS is 8.0 months (95%CI: 5.7-10.2). There is no difference in mPFS between arms (adjusted HR = 0.98, 95% CI: 0.82-1.18, P = 0.907). Methylated tumors had longer mPFS (HR=0.57, 95% CI: 0.39-0.83, P=0.004) irrespectively to the study treatment. Conclusions: There is not apparent benefit of continuing TMZ treatment for more than 6 cycles. Data will be actualized for the congress.Supported by a Grant of the ISCIII: PI13/01751. Clinical trial information: NCT02209948.

TPS503 Background: Perioperative treatment of muscle-invasive bladder carcinoma (MIBC) remains cisplatin-based chemotherapy, but recent evidences suggest that immune checkpoint inhibitors could be incorporated in this setting. Durvalumab is a PD-L1 blocking antibody active in advanced urothelial carcinoma pretreated with platinum-containing chemotherapy and currently under evaluation in first-line, both as monotherapy and in combination with tremelimumab. Olaparib is a PARP inhibitor especially important in tumors with deficiencies in DNA repair mechanisms. Preliminary results from combination trials suggest that these drugs could have synergistic effect dependent on an immunogenic modulation related with STING pathway, and an increase of neoantigens. Unexpected toxicities have not been described. Methods: Design: Open label phase II single arm clinical trial. Primary Objective: To assess the impact of neoadjuvant treatment with durvalumab plus olaparib in the molecular profile of MIBC. Secondary Objectives: Efficacy (Radiological and pathological responses); Safety. Exploratory objective: To identify predictive and prognostic biomarkers. Key correlative studies: Independent central pathologist for histological review and assessment of immunohistochemistry for PD1, PD-L1 and PD-L2; Genomic characterization (WES) and Expression assessment (RNAseq) of the tumors pre and post treatment; Assessment of soluble biomarkers and their evolution during the treatment: flow cytometry for immune cells; immunoassays for cytokines; HLA genotyping. Treatment: Durvalumab 1500 mg iv Q4W & Olaparib 150 mg bid orally during 6 to a maximum of 8 weeks pre-cystectomy. Recruitment: 29 patients. Collaborating institutions: 10 (members of Spanish Oncology Genitourinary Group). Key Inclusion Criteria: Subjects with histological confirmation of T2-T4a MIBC aimed for cystectomy without neoadjuvant chemotherapy; Available samples for correlative studies; Adequate medullary, renal and hepatic function. Key Exclusion Criteria: Use of immunosuppressive medication; Documented autoimmune disorders. Clinical trial information: NCT03534492.

There is a current unmet medical need for treatment of leptomeningeal metastases (LMD). To analyze the efficacy and safety of systemic temozolomide (TMZ) for first-line treatment of patients with LMD associated with solid tumors, a phase II, non-randomized, multicenter, prospective study was conducted. The planned duration of treatment was a maximum of six cycles (24 weeks) or until unacceptable toxicity was reported. One cycle of oral TMZ (100 mg/m(2) daily) consisted of one week on treatment/one week off treatment for four weeks. The study was stopped early because of poor accrual. Nineteen patients (median age 51(33-72); 32 % male) were enrolled. The LMD source was breast cancer (53 %) and non-small-cell lung cancer (37 %). Previous treatment was chemotherapy (100 %), surgery 74 %, radiotherapy 79 %, and hormone therapy 42 %. The average last dose of TMZ received by patients was 171 mg and only one patient required dose reduction. Three of 19 patients (15.8 %) had clinical benefit and 16 of 19 patients (84.2 %) progressed. Of the two patients completing the study (six cycles, 24 weeks), one had a partial response and the other stable disease. Median survival was 43 days (95 % CI 28.7-57.3); there were 18 deaths. Median TTP was 28 days (95 % CI 14-42). The most common adverse event was vomiting (52.6 %); nine patients (47.4 %) reported at least one serious adverse event but only one episode of thrombocytopenia was drug related. Median Karnofsky score remained at or above 70 % throughout the study, and was 75 % at the end of the study. First-line TMZ was well tolerated, and did not adversely affect the quality of life of patients with LMD. Future studies are needed to verify the efficacy results of this pilot trial.

Many studies have reported the benefits of Decongestive treatment in patients with breast-cancer-related lymphedema (BCRL) but few have study what are the predictive factors of response.We performed a prospective, multicenter controlled cohort study of 171 patients with BCRL to identify independent predictive factors of response to decongestive treatment (CDT). Demographic data and clinical and lymphedema characteristics were collected prospectively. The end point was the "percentage reduction in excess volume (PREV)." Volumes were measured prior and at the end of CDT. Factors associated with response (PREV) were tested in univariate and multivariate analyses using linear regression techniques.Median age was 60.4 years (range 32-84); mean lymphedema chronicity 4 years [95% confidence interval (95% CI): 3.1-5.0]; mean baseline excess volume (EV) was 936 mL (95% CI: 846-1026), and mean percentage EV was 35.3% (95% CI: 32.0-38.7); compliance to bandages was good in 81.3% of patients. PREV was 71.7% (95% CI: 65.2-78.2). After univariate screening, 11 variables were found to be associated with PREV but only 4 variables were independent predictive factors of response to CDT in the multivariate analysis: Venous insufficiency, percentage of EV (the higher the EV, the lower the reduction with CDT); compliance to bandages (a good compliance improved PREV in 25%), and treatment in autumn (better results than during the rest of the year).This study shows that compliance to bandages during CDT is one of the most important predictors of response. Moreover, data support the idea that more severe lymphedemas have a worse response to treatment, and it should be recommended in early stages. The association between the season of treatment and response was also very strong, so weather conditions are an additional factor that must be taken into account in further studies.

Docetaxel and erlotinib are used as second-line treatment of advanced non-small-cell lung cancer. With the aim of assessing whether sequential administration of both could avoid possible negative interactions and optimize the benefit obtained, a clinical trial was designed. Outcomes showed improved progression-free survival and disease control rates compared with erlotinib alone, proving the absence of antagonism between them on this basis. Introduction: The purpose of this study was to assess whether an intercalated dosing schedule of erlotinib and docetaxel could avoid possible negative interactions and optimize the benefit obtained as second-line therapy in non-small-cell lung cancer (NSCLC) patients. Patients and Methods: A phase II randomized clinical trial was designed for advanced NSCLC patients in whom previous chemotherapy treatment had failed. The experimental arm with 33 patients consisted of erlotinib 150 mg/d orally, intermittent administration on days 2 to 16 every 21 days, combined with docetaxel 75 mg/m(2) every 21 days; the control arm with 35 patients consisted of erlotinib 150 mg/d orally, administered continuously. The study's primary end point was the proportion of patients who remained progression-free at 6 months in the 2 arms. Results: The proportion of patients who remained progression-free at 6 months was of 5 patients (15%) in the intercalated arm and 3 patients (9%) in the erlotinib monotherapy arm respectively. Median progression-free survival (PFS) was 3.0 versus 2.1 months (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.39-1.06; P = .086). Median overall survival (OS) was 7.5 and 5.2 months (HR, 0.70; 95% CI, 0.41-1.19; P = .19). Disease control rates were 51.7% and 36.4%, respectively. No new safety signals were observed. Conclusion: Erlotinib and docetaxel with intermittent administration of erlotinib improved PFS, OS, and disease control rates compared with erlotinib alone. All of our results indicated that an intercalated dosing schedule of erlotinib and docetaxel could be more efficient than erlotinib treatment alone. Therefore, further studies should be developed in a larger number of patients. This study has shown the absence of antagonism between docetaxel and erlotinib when given in an intercalated fashion.

Neutropenia induced by chemotherapy (CT) is an infection risk factor associated to greater morbidity/mortality and dose-limiting toxicity that on many occasions requires a reduction of the dose of cytostatics or a delay in the administration of treatment. This may have a negative effect on the patient's quality of life and even diminish the efficacy of the treatment, especially when the intention is to cure or prolong survival. Management of treatment or prophylaxis of grade 3–4 neutropenia and febrile neutropenia with myeloid growth factors (CSF) varies very much in clinical practice, both in the time of starting treatment and the types of patients it is given to. The need to generalise and facilitate practice based on clinical evidence has led the Spanish Society of Medical Oncology (SEOM) to prepare clinical practice guidelines on the use of myeloid growth factors.

e17545 Background: CDDP+NVBO as induction and concomitant regimen with RT has shown good efficacy outcomes and safety profile (Krzakowski, J Thor Oncol. 2008). The objective of this study was to evaluate the effectiveness and toxicities of the combination of CDDP and NVBO given at full doses concomitantly with RT in LA-NSCLC. Methods: Between February 2010 and May 2011, 26 chemo-naive patients (p) with histologically confirmed stage IIIA/IIIB unresectable LA NSCLC were treated. Treatment consisted of 4 cycles (cy) of NVBO 60 mg/m2 on days 1 and 8 and CDDP 80 mg/m2 every 3 weeks plus RT 66 Gy starting on day 1, cy 2. A standard Fleming two stage design is being used. The sample size is calculated with a power of 90% and a two-sided type 1 error allowance of 5%. Stage 1 included 25 pts, with subsequent expansion to a total of 45. Results: Patient’s characteristics were: Median age, 59 years (range 48-71); males, 92%; smokers, 60%; adenocarcinoma, 28% / squamous, 64%; stage IIIA, 54% / IIIB, 46%. 21 p completed the 4 cy treatment as per protocol. We analyzed 92 cy. Hematological toxicities (% cy): grade (g) 3/4 neutropenia, 42.3%; g3 anemia, 3.3%; g3 thrombocytopenia, 2.2%; febrile neutropenia, 1 p. Non-hematological toxicities (% cy): g3 oesophagitis, 6.5%; g4 diarrhea, 1.1%. 21 p were evaluable for response. 1 CR (4.8%), 17 PR (81%) and 1 SD (4.5%) were reported. ORR 85.8%. Survival analysis has not been performed due to short follow-up. Conclusions: The findings of this interim analysis confirm the previously reported outcomes of efficacy and safety with NVBO plus CDDP when administered concurrently with RT in stage IIIA/IIIB p. The trial has met the criteria for continuation into stage 2.

e18036 Background: Patients (p) with advanced NSCLC have few treatment options after progressing to 1st-line platinum doublet chemotherapy (PDC). Several preclinical and phase I studies have suggested that sequential administration of erlotinib (E) and docetaxel could avoid possible negative interactions and optimize the benefit obtained against NSCLC. This randomized phase II was designed to address the clinical benefit obtained with the use of sequential administration of docetaxel and intermittent E. Methods: 70 p with advanced NSCLC progressing to previous PDC for advanced disease were randomized (1:1): Group A (n = 34): Docetaxel 75 mg/m2 day 1 and intermittent E (day 2-16), up to 4 cycles, followed by E in monotherapyGroup B (n = 36): E in monotherapy. Treatment was administered until unacceptable toxicity or progression. Primary endpoint: rate of p free of progression at 6 months; secondary endpoints: progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety. The st...

20607 Background: The purpose of this prospective, multicenter study was to develop a model to predict hematopoietic response (HR) to epoetin alfa (EA) in anemic patients with solid tumors receivin...