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The long-term clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) and a complete response (CR) to the tyrosine kinase inhibitor (TKI) sunitinib are poorly known. The characteristics of these patients could reveal previously undetected associations with clinical variables.This observational, retrospective study (ATILA) used data from a registry of patients with mRCC who had received first-line sunitinib and had achieved CR from 2007 to 2018 in Spain.Sixty-two patients with CR were included; 48 patients (77.4%) received sunitinib in monotherapy and 14 (22.6%) combined with or followed by local treatment. Median age was 58.5 years (range, 32-81). Most patients (79.0%) had clear cell histology and had undergone previous nephrectomy (90.3%). The majority (70.2%) had an intermediate IMDC prognosis, 23% favorable and 7.0% poor. The median time on treatment with sunitinib was 28.2 months (IQR, 16.7-41.0) and the median time to CR was 10.9 months (IQR, 7.2-19.3). After a median follow-up of 8 years (range, 3-13 years), the median PFS was not reached. The overall median duration of complete response was 64.1 months (IQR, 32.2-99.4). The tolerance and safety profile of sunitinib was consistent with previous reports.Durable CR to sunitinib was observed in patients regardless the prognosis group, metastasis site or histology type, with 75% of patients remaining in CR after 10 years.gov: NCT03916458.

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.

We aimed to compare the efficacy and safety of maintaining or withdrawing abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer who had experienced cancer progression to this treatment and were beginning a docetaxel-based therapy. Phase II, randomised, open-label study conducted in patients with metastatic castration-resistant prostate cancer who were asymptomatic or mildly symptomatic. After open-label treatment with AAP, patients who had experienced cancer progression to AAP were randomised to 75 mg/m2 of docetaxel plus AAP or to receive 75 mg/m2 of docetaxel plus 10 mg of prednisone orally daily. The primary outcome was the radiographic progression-free survival rate at 12 months as evaluated by the investigators in all randomised patients. A total of 148 patients were included in open-label treatment with AAP, and of them, 94 patients were randomised to receive either docetaxel plus AAP (intervention group; n = 47) or docetaxel plus prednisone (control group; n = 47). The 12-month radiographic progression-free survival rates did not differ between the intervention group (34.9%; 95% CI 20.7-49.2) and the control group (33.9%; 95% CI 19.5-48.3). There were no significant differences in the time to radiographic progression and the overall survival between the intervention and control groups. Grade 3-5 neutropenia with the combination of docetaxel plus prednisone and AA was more frequent than with docetaxel plus prednisone (59.6% versus 27.7%). Our results indicate that the therapeutic strategy of maintaining AAP added to docetaxel in chemotherapy-naïve patients who have experienced cancer progression to AAP treatment should not be further evaluated and should be avoided in clinical practice. NCT02036060 https://clinicaltrials.gov/ct2/show/NCT02036060.

To review current measures for renal cancer care and develop a comprehensive and updated list of measures for their practical use in Spain. The study was developed by Fundacion ECO, a Spanish foundation aiming to improve oncology quality of care. A systematic literature review was carried out to identify measures and knowledge gaps. A scientific committee composed of nine experts reviewed the literature findings and added measures. A preliminary list of 42 measures was evaluated with the Delphi method to gather feedback from 47 medical oncology experts in Spain. Experts scored the appropriateness of the measures and ranked their priority in two consecutive online surveys. The scientific committee reviewed the Delphi results and developed the measures. A technical group from Universidad Francisco de Vitoria conducted and oversaw the Delphi method. The Delphi method led to consensus on all 42 measures. The scientific committee used a prioritisation matrix to select 25 of these measures for evaluating quality of care in renal cancer. These measures regarded structure, process, and outcome and covered general management, diagnosis, treatment, follow-up, and evaluation of health outcomes. Easy-to-use index cards were developed for all 25 measures, including their definition, formula, acceptable level of attainment, and rationale. This manuscript aims to provide healthcare professionals with expert- and evidence-based measures that are useful for evaluating quality of care in renal cancer in Spain and cover all aspects and stages.

269 Background: In pts with advanced RCC, second-line treatment with LEN + EVE prolonged progression-free survival (PFS) compared with EVE alone. LEN + PEMBRO, also showed preliminary efficacious evidence in a phase 1/2 RCC study. Here, we describe the investigational study results of first-line LEN + PEMBRO or LEN + EVE versus SUN in pts with advanced RCC. Methods: Pts were randomized (1:1:1) to receive LEN 20 mg orally once daily + PEMBRO 200 mg IV every 3 weeks (wks); or LEN 18 mg + EVE 5 mg orally once daily; or SUN 50 mg orally once daily (4 wks on/2 wks off). Eligible pts had advanced RCC with no prior systemic therapy. Randomization was stratified by geographic region and MSKCC prognostic group. The primary endpoint was PFS by Independent Review Committee per RECIST v1.1. Secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. A sequential approach was used to test PFS first, then OS and ORR. PFS and OS were compared across arms by a stratified log-rank test; hazard ratios (HRs) were estimated by a stratified Cox regression model. Results: 1069 pts were randomized (Table). After a median follow-up of 27 months (data cutoff August 28, 2020), PFS was significantly improved with LEN + PEMBRO (median 24 months [mos]) vs SUN (median 9 mos; HR 0.39, 95% CI 0.32–0.49) and LEN + EVE (median 15 mos) vs SUN (HR 0.65, 95% CI 0.53–0.80). OS was significantly longer with LEN + PEMBRO vs SUN (HR 0.66, 95% CI 0.49–0.88), whereas OS with LEN + EVE vs SUN was not statistically different (HR 1.15, 95% CI 0.88–1.50). ORR was significantly greater with LEN + PEMBRO (ORR 71%; complete response [CR] 16%) vs SUN (ORR 36%; CR 4%; odds ratio 4.35, 95% CI 3.16–5.97) and LEN + EVE (ORR 54%; CR 10%) vs SUN (odds ratio 2.15, 95% CI 1.57–2.93). Grade ≥3 treatment-related adverse events occurred in 72% of pts in the LEN + PEMBRO arm and 73% of pts in the LEN + EVE arm compared with 59% of pts in the SUN arm. Conclusions: LEN + PEMBRO demonstrated significant improvements in PFS, OS and ORR vs SUN. LEN + EVE demonstrated significant improvements in PFS and ORR vs SUN. Safety was manageable and consistent with the known single-agent profiles. Clinical trial information: NCT02811861 . [Table: see text]

Objective: Our aim was to provide practical recommendations on the management of patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed after docetaxel plus androgen-deprivation therapy (ADT) or abiraterone plus ADT. Methods: Systematic literature review (SLR), nominal group meeting, and Delphi process. A panel of 12 experts was established who defined the scope, users, and sections of the document. We performed an SLR in order to assess the efficacy and safety of available drugs in patients with mCRPC. Abstracts from the American Society of Oncology and European Society for Medical Oncology meetings were also examined. The results were discussed during an expert meeting in which 14 recommendations were generated. The level of agreement with the recommendations was also tested by 13 additional experts following the Delphi process. Recommendations were voted by means of scores ranging from 0 (total disagreement) to 10 (total agreement). We defined agreement when at least 70% of the experts voted ⩾7. Next, we assigned a level of evidence and grade to the recommendation using the Oxford Centre for Evidence-based Medicine Levels of Evidence, following which the final document was drafted. Results: The literature search did not find any articles meeting the inclusion criteria. Finally, 13 out of 14 recommendations were accepted after two Delphi rounds (two were modified after the first round). They pertain to general and individual case-based treatment recommendations. Conclusions: In mCRPC patients who have progressed after docetaxel or abiraterone plus ADT in the metastatic hormone-sensitive prostate cancer setting, these recommendations may support treatment decision-making, due to the lack of evidence or other globally accepted sequencing algorithms.

Introduction Although increasing numbers of therapies with proven survival benefits have become available for metastatic castration-resistant prostate cancer (mCRPC), including radium-223, there is still a need for reliable biomarkers that provide information about clinically meaningful outcomes and treatment responses. Materials and Methods This study was a translational study that was conducted prospectively by the Spanish Oncology Genito-Urinary Group and included 45 patients with histologically confirmed mCRPC who were treated with radium-223. The primary response outcome was defined by a decline in circulating tumor cells (CTCs) of > 50% from baseline or a CTC count of ≤ 5 cells/7.5 mL at cycle 3 of radium-223. We also assessed response according to prostate-specific antigen and alkaline phosphatase levels. CTCs were evaluated as prognostic factor for treatment completion with radium-223 treatment. Kaplan-Meier estimates of survival were calculated for the global population and were correlated with biomarker response outcomes. Results Significantly, more patients with baseline CTC counts ≤ 5/7.5 mL, which are indicative of better prognoses, completed the 6 injections of therapy than those with CTC counts > 5 (16/22; 73% vs. 6/20; 30%, respectively; P = .012). The median overall survival was 16 months. Survival was significantly decreased in patients with baseline CTC counts > 5 cells/7.5 mL (7 months; P = .026) and baseline alkaline phosphatase levels ≥ 220 U/L (8 months; P = .028). Conclusions CTCs hold significant promise as a prognostic factor for survival and completing treatment prior to the initiation of bone-targeted radium-223 therapy. These findings may help to guide the use of radium-223 in patients with mCRPC.

Updated information published up to 2016 regarding major advances in renal cancer, bladder cancer, and prostate cancer is here presented. Based on an ever better understanding of the genetic and molecular alterations that govern the initial pathogenic mechanisms of tumor oncogenesis, an improvement in the characterization and treatment of urologic tumors has been achieved in the past year. According to the Cancer Genome Atlas (ATLAS) project, alterations in the MET pathway are characteristics of type 1 papillary renal cell carcinomas, and activation of NRF2-ARE pathway is associated with the biologically distinct type 2. While sunitinib and pazopanib continue to be the standard first-line treatment in metastatic renal cell carcinoma of clear cell histology, nivolumab and cabozantinib are now the agents of choice in the second-line setting. In relation to urothelial bladder carcinoma, new potential molecular targets such as FGFR3, PI3K/AKT, RTK/RAS, CDKN2A, ARIDIA, ERBB2 have been identified. Response to adjuvant cisplatin-based chemotherapy appears to be related to basal, luminal, and p53-like intrinsic subtypes. A phase II study with eribulin and a maintenance phase II trial with vinflunine have shown promising results. Similarly, the use of the check point inhibitors in advanced disease is likely to revolutionize the management of patients who have progressed after cisplatin-based chemotherapy. In prostate cancer, seven mutually exclusive molecular subtypes have been identified by the TCGA project. Chemotherapy has been consolidated as a key treatment for castration-sensitive metastatic prostate cancer, and abiraterone, enzalutamide, cabazitaxel, and radium-223 remain standard therapeutic options for men with metastatic castration-resistant prostate cancer. All this progress will undoubtedly contribute to the development of new treatments and therapeutic strategies that will improve the survival and quality of life of our patients.

The management of genitourinary cancer, including bladder, prostate, renal and testicular cancer, has evolved dramatically in recent years due to a better understanding of tumour genetic mutations, alterations in molecular pathways, and to the development of new kinds of drugs such as targeted therapies and immunotherapies. In the field of immunotherapy, new drugs focused on stimulating, enhancing and modulating the immune system to detect and destroy cancer, have been recently discovered. Research in oncology moves quickly and new data of great relevance for clinical practice are communicated every year. For this reason, a group of experts, focused exclusively on the treatment of genitourinary tumours and who get together every year in the BestGU conference to assess the latest progress in this field have summarized the most important advances in a single review, along with a critical assessment of whether these results should alter daily clinical practice.

Càncer; Immunoteràpia; Ronyó Cáncer; Inmunoterapia; Riñón Cancer; Immunotherapy; Kidney In this article, we review de state of the art on the management of renal cell carcinoma (RCC) and provide recommendations on diagnosis and treatment. Recent advances in molecular biology have allowed the subclassification of renal tumours into different histologic variants and may help to identify future prognostic and predictive factors. For patients with localized disease, surgery is the treatment of choice with nephron-sparing surgery recommended when feasible. No adjuvant therapy has demonstrated a clear benefit in overall survival. Considering the whole population of patients with advanced disease, the combination of axitinib with either pembrolizumab or avelumab increase response rate and progression-free survival, compared to sunitinib, but a longer overall survival has only been demonstrated so far with the pembrolizumab combo. For patients with IMDC intermediate and poor prognosis, nephrectomy should not be considered mandatory. In this subpopulation, the combination of ipilimumab and nivolumab has also demonstrated a superior response rate and overall survival vs. sunitinib. In patients progressing to one or two antiangiogenic tyrosine-kinase inhibitors, both nivolumab and cabozantinib in monotherapy have shown benefit in overall survival compared to everolimus. Although no clear sequence can be recommended, medical oncologists and patients should be aware of the recent advances and new strategies that improve survival and quality of life in patients with metastatic RCC.

Background To describe the patterns of second-line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel treatment in a Spanish population, to identify the factors associated with those patterns, and to compare the efficacy and safety of the treatments most frequently administered. Methods Observational, prospective study conducted in patients with histologically or cytologically confirmed prostate adenocarcinoma; documented metastatic castration-resistant disease; progression after first-line, docetaxel-based chemotherapy with or without other agents. Results Of the 150 patients recruited into the study, 100 patients were prescribed abiraterone acetate plus prednisone (AAP), 44 patients received cabazitaxel plus prednisone (CP), and 6 patients received other treatments. Age (odds ratio [OR] 1.06, 95% [confidence interval] CI 1.01 to 1.11) and not elevated lactate dehydrogenase (LDH) levels (OR 0.33, 95% CI 0.14 to 0.76) were independently associated with the administration of AAP. Treatment with AAP was associated with significantly longer clinical/radiographic progression-free survival (hazard ratio [HR] 0.57, 95% CI 0.38 to 0.85) and overall survival (OS; HR 0.40, 95% CI 0.21 to 0.76) compared to CP, while no significant differences between the treatments were found regarding biochemical progression-free survival (PFS; HR 0.78 [95% CI 0.49 to 1.24]). However, in a post-hoc Cox regression analysis adjusted for potential confounders there were not differences between AAP and CP in any of the time-to-event outcomes, including overall survival. We observed no new safety signals related to either regimen. Conclusion Second-line AAP for patients with mCRPC is the most common treatment strategy after progression with a docetaxel-based regimen. When controlling for potential confounders, patients receiving this treatment showed no differences in PFS and OS in comparison to those receiving CP, although these latter results should be confirmed in randomized controlled trials., This study was funded by Janssen Cilag S.A. Janssen-Cilag S.A. was involved in the design of the study, interpretation of data, and in writing the manuscript. Quality control and statistical analyses were performed by a contract research organization that was funded by Janssen-Cilag S.A.

4502 Background: LEN + PEMBRO improved PFS, OS and ORR vs SUN in the first-line treatment of pts with aRCC; LEN + EVE improved PFS and ORR vs SUN (Motzer R et al. NEJM. 2021). We report results of a secondary objective of the CLEAR trial comparing the impact of LEN + PEMBRO or EVE vs SUN, on HRQoL. Methods: Pts (N=1069) were randomized (1:1:1) to receive LEN 20 mg PO QD + PEMBRO 200 mg IV Q3W; LEN 18 mg + EVE 5 mg PO QD; or SUN 50 mg PO QD (4 wks on/2 wks off). HRQoL was assessed per FKSI-DRS, EORTC QLQ-C30, and EuroQoL EQ-5D-3L, at baseline, on day 1 of subsequent 3 wk cycles starting with cycle 2, and at the off-treatment visit. HRQoL analyses (unless otherwise noted) were based on data from randomized pts with any HRQoL data who received ≥1 dose of study treatment. No adjustments for multiple testing or estimation were used; P-values and CIs are nominal and descriptive. Results: For comparisons of LEN + PEMBRO vs SUN, overall changes from baseline at mean follow-up (wk 46) favored LEN + PEMBRO with significant differences between treatments for physical functioning (least squares mean difference [LS MD] [95% CI]: 3.0 [0.5, 5.5]) and fatigue (−2.8 [−5.5, −0.1]), dyspnea (−2.8 [−5.3, −0.3]), and constipation (−2.2 [−4.2, −0.2]). LS MD of the FKSI-DRS total score was 0.2 (−0.4, 0.7). For comparisons of LEN + EVE vs SUN, overall changes from baseline at wk 46 favored SUN with significant differences in overall HRQoL (−2.8 [−5.1, −0.5] assessed by the EORTC QLQ-C30 GHS/QoL scale) and pain (2.8 [0.1, 5.5]), appetite loss (4.2 [1.3, 7.1]), and diarrhea (5.3 [2.6, 7.9]). LS MD of the FKSI-DRS total score was −0.4 (−1.0, 0.2). 14 of 18 scales for both LEN + PEMBRO and LEN + EVE vs SUN had no significant differences in LS MD comparisons. The LEN + PEMBRO arm is favored over SUN for the median time to first deterioration (TTD) for physical functioning, dyspnea, appetite loss and EQ-5D VAS (Table). 15 of 19 scales for both LEN + PEMBRO and LEN + EVE vs SUN had no significant differences in TTD comparisons. Conclusions: Compared with SUN, pts in LEN + PEMBRO group had similar or better symptoms and HRQoL. Clinical trial information: NCT02811861. [Table: see text]

4511 Background: Savolitinib is a potent and selective MET inhibitor with activity in MET-driven papillary renal cancer (PRC). Durvalumab is a PD-L1 inhibitor which has been tested in combination with savolitinib in metastatic PRC with response rates of 29% (12/41). Here we describe the efficacy of this combination in MET-driven metastatic PRC. Methods: This single arm phase I/II trial explored durvalumab (1500mg Q4W) and savolitinib (600mg OD) together in metastatic PRC, with a 4wk savolitinib run in. Biomarker analysis results were compared with responses to treatment as planned in the protocol. The analysis presented here focuses on those patients with MET DNA alterations (central analysis:chromosome 7 gain/MET or HGF amplification/MET kinase domain mutations). Confirmed response rate (RR) (RECIST v1.1), progression-free survival (PFS), tolerability (CTCAE v4.03) and overall survival (OS) were analysed. Results: 42 patients were enrolled in the metastatic papillary cohort, of which 41 patients received treatment. The median follow up was 26.8 months. The confirmed RR was 29% (12/41) and median PFS was 4.9 months (95% CI 2.5-10.0). 14/41 (34%) of these patients had MET-driven disease. 71% (10/14) of MET-driven patients had not previously received systemic therapy and 7% (1/14) were PD-L1 positive. IMDC good, intermediate, and poor risk disease occurred in 36% (5/14), 57% (8/14), and 7% (1/14) of MET-driven patients respectively. Confirmed RR in MET-driven patients was 57% (8/14) with duration of response at 9.4 months (95% CI 3.9-Not reached [NR]). Median PFS and OS in MET-driven patients were 10.5 months (95% CI 2.9-15.7) and 27.4 months (95% CI 7.3-NR) respectively. No new safety signals were seen. Conclusions: The combination of savolitinib and durvalumab has clinical activity in MET-driven PRC. A randomised phase III study is planned based upon these data. Clinical trial information: NCT02819596.

220 Background: The ECO Foundation (Excellence and Quality in Oncology) proposes to establish a set of healthcare quality measures (including indicators and standards) for the diagnosis, treatment and follow-up of renal cancer in Spain which all healthcare professionals involved can assume, being suitable for implementation in the continuous improvement process of our healthcare system. Methods: a) International literature review on the quality of healthcare in renal cancer; b) multidisciplinary driving group (9 oncologists with expertise in renal cancer plus 2 methodologists) to identify and choose possible quality measures to be applied in Spain; c) global evaluation of the relevance of these measures through experts’ consensus (Delphi modified by a stratified state panel, n = 55 oncologists specialized in renal cancer); d) selection of definitive measures, according to their feasibility and efficiency (information provided/effort in obtaining it) using a quantitative online priority grid; e) standard wording of the chosen measures: definition, indicator, sources of information, exclusions, clarifications, categorization and acceptable standard. Results: The nominal group proposed 43 quality measures for the Delphi panel. Consensus agreement rate = 84.5% (47/55). The professional consensus was reached on 40 measures (4 structural, 33 in healthcare procedures and 3 in clinical results). Therefore, there is a high level of consensus (93%) among Spanish oncologists who specialize in renal cancer on the content of the healthcare quality measures in the management of renal cancer. The final measures were chosen using a high confidence level (95%) in the unanimity of the experts (oncologists in the driving group) for prioritization depending on the feasibility and efficiency in the healthcare system. Finally, 25 measures were chosen (2 structural, 20 in procedures and 3 in results). Conclusions: The level of consensus and prioritization of measures achieved, will most likely translate in a widespread acceptance and viability for implementation in the National Health System. This could provide a valuable tool for quality assessment and equality in the care of renal cancer patients in Spain.

5060 Background: Immunotherapy (IO)-based combinations have replaced tyrosine kinase inhibitors (TKI) as standard upfront treatment of metastatic RCC pts. Selection of 2L treatment after progression to novel combinations in 1st-line (1L) is mostly based on retrospective series or subgroups analysis of randomized trials. We aim to evaluate the activity and safety of sunitinib in advanced RCC after progression on an IO-based 1L approach. Methods: This is a prospective, non-randomized, open-label and multicenter phase II study. Pts with ECOG 0-2 and locally advanced or metastatic RCC after treatment in 1L with a prior PD-1 and/or PD-L1 and/or CTLA-4 inhibitor were included. Sunitinib was administered at 50 mg/day on a 4/2 schedule until disease progression. Primary endpoint was overall response rate (ORR) by RECIST v 1.1 criteria. Results: Twenty pts were enrolled in the study. Median age was 66 yo, 70% had intermediate prognosis by Heng's scale, and 88% ECOG 1. 45% of pts received atezolizumab, 30% pembrolizumab, 20% nivolumab and 15% ipilimumab-based regimens as 1L. ORR to 1L treatment was 45%. Median time from end of 1L to sunitinib onset date was 1.1 months (0.3-22.1). Two (10%) pts had partial response with sunitinib and 11 (55%) stable disease for a total disease control rate of 65%. With a median follow-up of 8.8 months, median PFS was 6.8 months (0.0-13.9) and median OS 13.6 months (10.5-16.6). Median duration of treatment was 4 months (0.9-16-2). Most common treatment-related adverse events, all grades, were asthenia (55%), dysgeusia (35%), diarrhea (30%), hypertension (30%), mucosal inflammation (25%), palmar-plantar erythrodysesthesia (25%), anemia (20%), neutropenia (20%) and nausea (15%); grade 3 were asthenia (15%), hypertension (10%) and neutropenia (10%). Conclusions: To our knowledge, the INMUNOSUN trial is the first study to evaluate prospectively the activity of a single agent TKI in a pure 2L setting of metastatic RCC pts treated with an IO-based approach upfront. ORR and PFS with sunitinib seem lower than expected when used as a 1L. Consistency in toxicity profile was observed. Clinical trial information: NCT03066427 .

Recent data suggested that plasma Ghrelin O-Acyl Transferase enzyme (GOAT) levels could represent a new diagnostic biomarker for prostate cancer (PCa). In this study, we aimed to explore the diagnostic and prognostic/aggressiveness capacity of GOAT in urine, as well as to interrogate its putative pathophysiological role in PCa. We analysed urine/plasma levels of GOAT in a cohort of 993 patients. In vitro (i.e., cell-proliferation) and in vivo (tumor-growth in a xenograft-model) approaches were performed in response to the modulation of GOAT expression/activity in PCa cells. Our results demonstrate that plasma and urine GOAT levels were significantly elevated in PCa patients compared to controls. Remarkably, GOAT significantly outperformed PSA in the diagnosis of PCa and significant PCa in patients with PSA levels ranging from 3 to 10 ng/mL (the so-called PSA grey-zone). Additionally, urine GOAT levels were associated to clinical (e.g., Gleason-score, PSA levels) and molecular (e.g., CDK2/CDK6/CDKN2A expression) aggressiveness parameters. Indeed, GOAT overexpression increased, while its silencing/blockade decreased cell-proliferation in PCa cells. Moreover, xenograft tumors derived from GOAT-overexpressing PCa (DU145) cells were significantly higher than those derived from the mock-overexpressing cells. Altogether, our results demonstrate that GOAT could be used as a diagnostic and aggressiveness marker in urine and a therapeutic target in PCa.

Background Radium‐223 dichloride (radium‐223) is approved for patients with castration‐resistant prostate cancer (CRPC), symptomatic bone metastases, and no visceral disease using a dosing regimen of 6 injections (55 kBq/kg intravenously; 1 injection every 4 weeks). Early results from international, open‐label, phase 1/2 study NCT01934790 showed that re‐treatment with radium‐223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from 2‐year follow‐up of the radium‐223 re‐treatment study. Methods Patients with CRPC and bone metastases who completed 6 initial radium‐223 injections with no disease progression in bone and later progressed were eligible for radium‐223 re‐treatment (up to 6 additional radium‐223 injections), provided that hematologic parameters were adequate and chemotherapy had not been administered after the initial course of radium‐223. Concomitant cytotoxic agents were not allowed during re‐treatment but were allowed at the investigator's discretion during follow‐up; other concomitant agents for prostate cancer (including abiraterone acetate or enzalutamide) were allowed at investigator's discretion. The primary objective was safety. Exploratory objectives included time to radiographic bone progression, radiographic progression‐free survival (rPFS), time to total alkaline phosphatase (tALP), and prostate‐specific antigen (PSA) progression, overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE‐free survival, all calculated from re‐treatment start. Evaluation of safety and exploratory efficacy objectives included active 2‐year follow‐up. Safety results from active follow‐up and updated efficacy are reported. Results Overall, 44 patients were re‐treated with radium‐223; 29 (66%) completed all 6 injections, and 34 (77%) entered 2‐year active follow‐up, during which no new safety concerns and no serious drug‐related adverse events were noted. rPFS events (progression or death) occurred in 19 (43%) of 44 patients; median rPFS was 9.9 months. Radiographic bone progression occurred in 5 (11%) of 44 patients. Median OS was 24.4 months. Median times to first SSE and SSE‐free survival were 16.7 and 12.8 months, respectively. Median time to tALP progression was not reached; median time to PSA progression was 2.2 months. Conclusions Re‐treatment with radium‐223 in this selected patient population was well tolerated, led to minimal hematologic toxicity, and provided continued disease control in bone at 2‐year follow‐up.

619 Background: There is a strong rationale for investigating MET and PD-L1 inhibition in metastatic papillary renal cancer (PRC). We previously reported response rates (RR) and progression free survival (PFS) for savolitinib (MET inhibitor) and durvalumab (PD-L1 inhibitor) together. Here we report overall survival (OS) data available 12 months after the last patient was enrolled. Methods: This single arm phase I/II trial explores durvalumab (1500mg Q4W) and savolitinib (600mg OD) together in PRC, with a 4wk savolitinib run in. Treatment naïve or previously treated patients with metastatic PRC were included. Confirmed RR (RECIST v1.1), PFS, tolerability (CTCAE v4.03) and overall survival (OS) were analysed. MET and PD-L1 biomarkers were explored (NCT02819596). Results: 42 patients were enrolled with 41 receiving at least one dose of study treatment. Safety and efficacy analyses were performed on these 41 patients. The median follow up was 14.3 months. IMDC good, intermediate and poor risk disease occurred in 29%, 63%, and 7% of patients respectively. Overall confirmed RR was 27% while median PFS was 4.9 months (95% CI: 2.5 – 12.0 months). Median OS was 12.3 months (95% CI: 5.8 – 21.3 months). Confirmed RR and median OS in the previously untreated cohort (N=27) were 33% and 12.3 months (95% CI: 4.7 – not reached (NR) months) respectively. Treatment related Grade 3/4 toxicity occurred in 34% of patients. No new safety signals were seen. PD-L1 and MET expression were not associated with higher RR (25% and 40% respectively) or longer OS. Conclusions: The combination of savolitinib and durvalumab has clinical activity in PRC and outcomes were not enhanced in biomarker positive cancers. Clinical trial information: NCT02819596.

488 Background: UTUC is rarer than bladder UC and typically responds poorly to standard chemotherapy. Analysis of 220 biomarker-evaluable atezo-treated patients (pts) in phase II/III trials suggested worse outcomes in UT vs lower tract UC [Galsky, ESMO 2018]. We explored clinical outcomes in pts with UTUC (renal pelvis or ureter) treated with atezo in the SAUL study. Methods: The single-arm SAUL study (NCT02928406) [Sternberg, Eur Urol 2019] enrolled a broader pt population, including pts with poor clinical characteristics and/or immune-mediated conditions, more representative of real-world practice than typically enrolled in randomized phase III immunotherapy trials. Pts with urinary tract carcinoma received atezo 1200 mg q3w until disease progression/unacceptable toxicity. Baseline characteristics, safety and efficacy were analyzed in subgroups of pts with UTUC (subdivided into renal pelvis or ureter UC) vs bladder UC. Results: Baseline characteristics in the 4 subgroups were generally similar, except for a numerically lower proportion of pts with 0 prior lines of therapy for metastatic disease in the UTUC vs bladder UC subgroup (30% vs 41%). Treatment exposure, safety and efficacy are shown below. Conclusions: These exploratory analyses of SAUL showed very similar efficacy and safety in UT vs bladder UC. This provides reassurance that atezo is active and has an acceptable safety profile in pts with UTUC, who are generally expected to have worse outcomes than bladder UC pts. Clinical trial information: NCT02928406 . [Table: see text]

95 Background: Abiraterone acetate (AA) improves OS and rPFS in first line mCRPC patients (pts). After AA progression D is commonly used as standard second line therapy. However, the value of maintaining AA in combination with D despite progression has not been tested beyond small exploratory studies (Tagawa ST, Eur Urol 2016) ABIDO is a randomized-phase II trial that evaluates efficacy and safety of D + AA vs D after first-line AA progression in mCRPC. Methods: Asymptomatic or minimally symptomatic mCRPC pts with no visceral metastases, ECOG PS 0-1, and adequate organ functions were included. The study has two stages: In stage I pts receive AA (1000 mg/d + prednisone (P) 10 mg qd) until radiological or unequivocal clinical progression. In stage II pts were randomized to D 75 mg/m2 q3wk in combination with AA 1000 mg/d (arm A) or without AA (arm B) The primary endpoint was rPFS and the secondary endpoints radiological response (RR), OS, PSA-response, PSA-PFS and safety. Results: 88 pts were randomized, (46 arm A, 42 Arm B). Median age was 69 y/o, 43% had ECOG 0 and 91%/11%/5% had bone, liver and lung metastases. Median rPFS was 11.4 months (m) in arm A vs 10.5 m in ARM B; 12-m rPFS was 43% vs 45%; Median PSA PFS was 6.2 vs 5.5 m and median OS was 17.3 vs 16.9 m. Twenty four pts (52%) in arm A and 19 (46%) in arm B achieve ≥50% PSA response. RR was achieved in 15% vs 7% of pts and disease control rate in 74% in both arms. No statistically significant differences were found in efficacy parameters. Half of pts received 10 cycles of D (median 7 and 8). D median dose intensity was 86% and 90% for each arm and 91% for AA. Eleven pts discontinued treatment due to non-hematological toxicity, 5 in arm A and 6 in arm B. Most frequent G3-4 toxicities per arm (A/B) were: neutropenia (57%/29%; P=0.027), febrile neutropenia (17%/10%), diarrhea (9%/7%), and asthenia (11%/10%). Conclusions: ABIDO trial was unable to demonstrate the significant clinical benefit of maintenance AA approach + D after AA first-line therapy. No differences were observed in RR, PSA PFS, rPFS and OS. In AA + D cohort, more frequent and severe hematological toxicity (neutropenia and febrile neutropenia) were reported. Clinical trial information: NCT02036060.

The conflict of interest declaration was published incorrectly in the original version.

[Abstract] Background: Several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. Patients and methods: Multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)≥22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset). Objectives were to compare baseline clinical factors in both populations and to correlate tumor expression of selected signaling pathways components with sunitinib PFS. Results: 123 patients were analyzed (97 LR, 26 PR). In the LR cohort, overall response rate was 79% and median duration of best response was 30 months. Median PFS and overall survival were 43.2 (95% confidence intervals[CI]:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At baseline PR patients had a significantly lower proportion of nephrectomies, higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time to and higher presence of metastases, and increased Fuhrman grade. Higher levels of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated populations significantly (AUC[ROC]=0.704; cut-off=34.85). Increased levels of hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged survival. No statistical significant associations between hsa-miR-23b or hsa-miR-27b and the expression of c-Met were found. Conclusions: Certain mRCC patients treated with sunitinib achieve extremely long-term responses. Favorable baseline hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p could be potentially used as biomarkers of sunitinib response. PPfizer; SOGUG-2011-05 Ministerio de Economía, Industria y Competitividad; SAF2015-66015-R Ministerio de Economía, Industria y Competitividad; ISCIII-RETIC RD12/0036/0009 Ministerio de Economía, Industria y Competitividad; PIE 15/00076

Bone metastases occur in 50% of patients with renal cell carcinoma, approximately 15% of these occur in the spine. In patients with disseminated disease with osseous metastases in vertebral bodies without options for curative treatment, cement injection in the vertebrae can be a useful tool in the management of pathologic fractures by allowing stabilization of the spine and ameliorating pain. A potential contraindication to this procedure is posterior vertebral wall involvement due to increased risk of cement leakage into the epidural space. In some of these cases, embolization with PVA particles and/or surgery is necessary. We present a case of lumbar spine metastases from renal cell carcinoma, with posterior wall involvement, that was treated by endovascular embolization using Onyx polymer. To the best of our knowledge, embolization of this kind of lesion, using this embolic agent, has not been previously reported.

5071Background: Germline mutations in BRCA2 have been identified in 3-5% of mCRPC patients. PROREPAIR-B (Castro et al ESMO 2017) is the first prospective study to report a worse survival from mCRPC...

178 Background: Radium-223 (Ra-223) treatment (tx) is indicated for patients (pts) with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases (mets) (6 × 55 kBq/kg IV injections [inj]; 1 inj q4wk). Early results of an international, open-label, phase 1/2 study (NCT01934790) showed that re-treating pts with Ra-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from a 2-year follow-up. Methods: Pts with CRPC and bone mets who completed 6 initial Ra-223 inj with no disease progression in bone and later progressed were eligible for Ra-223 re-tx (6 additional Ra-223 inj), provided that hematologic parameters were adequate. No concomitant cytotoxic agents were allowed; other concomitant agents (eg, abiraterone, enzalutamide) were allowed at investigator discretion. The primary objective was safety. Exploratory objectives were time to radiographic bone progression, radiographic progression-free survival (rPFS), overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-tx start. Pts will be followed for safety up to 7 years after last Ra-223 dose; an active 2-year follow-up evaluated exploratory objectives. Safety results from the active follow-up period and updated efficacy are reported. Results: 44 pts were re-treated with Ra-223; 29 (66%) completed all 6 inj (median number inj = 6). 34 (77%) of 44 pts entered active follow-up, during which no new safety concerns were noted. One new primary malignancy was reported (basal cell carcinoma). There were no serious drug-related adverse events. 19 (43%) of 44 pts had an rPFS event (radiographic progression or death); median rPFS was 9.9 months. Only 5 (11%) of 44 pts had radiographic bone progression; median time to radiographic bone progression was not reached. Median OS was 24.4 months. Median time to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Conclusions: Re-treating with Ra-223 was well tolerated in this select pt population, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up. Clinical trial information: NCT01934790.

Background: The impact of such recommendations after their implementation of guidelines has not usually been evaluated. Herein, we assessed the impact and compliance with the Spanish Oncology Genitourinary Group (SOGUG) Guidelines for toxicity management of targeted therapies in metastatic renal cell carcinoma (mRCC) in daily clinical practice. Methods: Data on 407 mRCC patients who initiated first-line targeted therapy during the year before and the year after publication and implementation of the SOGUG guideline program were available from 34 Spanish Hospitals. Adherence to SOGUG Guidelines was assessed in every cycle. Results: Adverse event (AE) management was consistent with the Guidelines as a whole for 28.7 % out of 966 post-implementation cycles compared with 23.1 % out of 892 pre-implementation cycles (p = 0.006). Analysis of adherence by AE in non-compliant cycles showed significant changes in appropriate management of hypertension (33 % pre-implementation vs. 44.5 % post-implementation cycles; p < 0.0001), diarrhea (74.0 % vs. 80.5 %; p = 0.011) and dyslipemia (25.0 % vs. 44.6 %; p < 0.001). Conclusions: Slight but significant improvements in AE management were detected following the implementation of SOGUG recommendations. However, room for improvement in the management of AEs due to targeted agents still remains and could be the focus for further programs in this direction., This study was funded by Pfizer, S.L.U. Medical writing assistance was provided by Esther Tapia, PhD and was founded by Pfizer. The authors gratefully say thanks to Ma Luz Samaniego for his help with the statistical analyses.

Today the use of adjuvant treatment of breast cancer is unquestionable in the management of this disease. Both chemotherapy and hormonal therapy have proved to be beneficial, not only with respect to the reduction of the risk of recurrence, but also with respect to mortality. However, in elderly patients, this therapeutic approach is occasionally the subject of controversy, due to the undervaluing of the tumoral disease with respect to the multiple pathology frequently present in these patients. This study analyses a retrospective series of 100 patients more than 70 years old with breast cancer who underwent radical surgery between 1990 and 1998, with an extension study without evidence of metastasis and a minimum follow-up of 2 years. As occurs in the population of this age, in our series 77% of the patients presented with concomitant disease under medical treatment, and although the majority received adjuvant treatment with tamoxifen, the principal cause of death in this series was the breast cancer that had been diagnosed.

e16536 Background: AA improves OS and rPFS in asymptomatic/minimally symptomatic mCRPC patients. D is currently one of the standard treatments after progression to AA. However, the value of maintaining AA along with D despite progression to AA has not been tested. ABIDO trial aims to evaluate efficacy and safety of AA + D maintenance after disease progression to first line AA in mCRPC. Clinicopathologic features associated with rPFS during first line AA are presented. Methods: ABIDO trial is a randomized, phase II, open-label study with two stages. In stage I pts receive AA (1000 mg + prednisone (P) 10 mg qd) until progressive disease. In the stage II pts will be randomized to receive three-weekly D 75 mg/m2plus P 10 mg/d with (arm A) or without (arm B) AA 1000 mg/d. Pts had no visceral metastases, ECOG PS 0-1, and adequate organ functions. Clinicopathological predictors for rPFS to first line AA were estimated using the Kaplan-Meier method and independent associations were evaluated using Cox regression models. Results: 143 pts were included. Analyzed variables were: median age was 70y, 60% of pts had ECOG 0, 84% bone metastases (18% > 4), 42% BPI score 2-3, 53% Gleason > = 8, 30% PSA > 80 ng/mL, 38% node involvement and 11% had at least one lymph node > = 3 cm; 53% of pts achieved 4 weeks PSA reduction > 50%.Median rPFS was 18 months. Univariate analysis identified as significant variables: PSA, BPI, Gleason, node involvement, 4 weeks PSA reduction > 50%, and total volume of lymph node metastasis. On multivariate analysis, BPI (0-1 vs 2-3) (hazard ratio [HR] 1.81; p = 0.039), Gleason ( < 8 vs > = 8) (HR 2.51; p = 0.005), node involvement (no nodes, nodes < 3 cm and at least 1 node > = 3 cm (HR 2.8; p = 0.001 and 3.57; p = 0.009) and PSA reduction > 50% (HR 3.06; p < 0.001) were independently associated with rPFS. Median rPFS was superior in pts with 3 or more good prognostic factors (14m vs not reached; p < 0.001). Conclusions: BPI, Gleason, node involvement and 4-week PSA response were identified as independent prognostic factors for rPFS in first line AA treated patients. Clinical trial information: NCT02036060.

227 Background: Recently treatment options for mCRPC have increased considerably. It remains unclear if there is any predictive factor to recognize which patients (pts) could obtain the most benefit in second line (2L) mCRPC. Recent data have been published addressing long-term predictive factors in a retrospective cohort in 2L1. We aim to reproduce it in this prospective study. Methods: The CAPRO study is a prospective multicenter national observational descriptive study. The primary endpoint was to describe the management in 2L mCRPC pts after DOC in routine clinical practice. To characterize which factors are associated with a better response in 2L mCRPC, we performed a multivariant analysis in the subgroup of pts with a long-term response (long-term responders (LTR): pts receiving abiraterone acetate + prednisone (AA) or Cabazitaxel (CB) for > 12 mo). Results: 150 patients were recruited (Jul 2013-Jan 2015). We identified 36 LTR (29/100 with AA: (29%) and 7/44 (15.9 %) with CB as 2L. No statistical differences in the number of LTR treated with AA vs CB (p = 0.095) were observed. LTR group (before starting 2L): median age 77.2 (51-87) median PSA 56.7 ng/dL (5.3-2627 ng/dL), alkaline phosphatase 92.5 IU/L (44-630 IU/L) and LDH 221.5 IU/L (147-445 IU/L). At median follow-up of 7.8 mo (IQR 4.2- 12.8), median PFS (clinical and/or radiological) was significantly longer in LTR AA group (not yet reached) vs LTR CB group 18.14 [95% CI 12.67-23.6]; HR 0·29 [95% CI 0,092 – 0,918; p = 0.025]. In a multivariate analysis two factors were significantly associated with LTR in 2L mCRPC: Gleason score < 7 (OR: 0.22 95% CI 0.065-0.745, p = 0.015) and normal LDH ( < 250 IU/L) (OR: 0.235, 95% CI 0.093-0.595, p = 0.002). No differences in safety profile between LTR vs non LTR of AA group and CB group were found. Conclusions: In this final subgroup analysis we observed Gleason score < 7 and LDH < 250 IU/L are predictors of long term response in 2L mCRPC. Median PFS in LTR treated with AA was significantly longer than LTR treated with CB. These findings need to be validated in further larger prospective studies.

[Abstract] 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/m(2) 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/m(2), 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.

Re-activation of the hepatitis B virus is very unusual, but has been described as a complication of chemotherapy. Most reported cases are related to haematological malignancies and, occasionally, to solid tumours.

e16080Background: Normal and pathological angiogenesis is under the control of various developmental genetic programs, including Notch and Hedgehog pathways. More recently, miRNAs have emerged as k...

5074Background: Radium-223 (Ra-223) treatment (tx) with 6 injections (inj) given at 4-week intervals is indicated for patients (pts) with castration-resistant prostate cancer (CRPC) and symptomatic...

5058Background: Abiraterone acetate (AA) improves OS and rPFS in asymptomatic/minimally symptomatic mCRPC patients (pts) who are chemotherapy (CT) naive through CYP17 inhibition. Upon progression t...

Treatment options for metastatic renal cell carcinoma (mRCC) have evolved very rapidly, as reflected by the approval of the many drugs that have shown efficacy in phase III studies. Approved drugs include tyrosine kinase inhibitors (TKI) such as sunitinib, sorafenib and pazopanib, vascular endothelial growth factor inhibitors such as bevacizumab, and mammalian target of rapamycin (mTOR) inhibitors such as temsirolimus and everolimus. These biological agents have toxicity profiles that differ from those accompanying current chemotherapeutic agents, but their novelty leads to a lack of exhaustive clinical data regarding related adverse events (AEs), whose symptoms may overlap with those of the chronic illnesses of patients with mRCC such as hypertension, hyperglycemia, and pneumonitis. Hypertension, hypothyroidism, hand–foot syndrome, and fatigue are AEs frequently associated with TKIs; whereas immunosuppression, stomatitis, metabolic alterations, and non-infectious pneumonitis are AEs of mTOR inhibitors. Recommendations for treating these adverse events in patients with mRCC are usually the same as those for the general population. Mild to moderate toxicities may be managed with supportive and pharmacologic interventions, but higher-grade toxicities usually require external specialist consultation, dose reductions, and treatment interruption or discontinuation. Some groups of patients with mRCC, such as frail, elderly patients, and patients with renal or liver dysfunction, require special management of AEs.

229 Background: Novel agents, such as abiraterone (A), cabazitaxel (CZ), and enzalutamide are currently available for the treatment of docetaxel (D)-treated metastatic castration resistant prostate cancer (mCRPC). The sequencing approach following D progression is still unknown. We now explore which factors are driving sequencing decisions in routine clinical practice in Spain. Methods: A prospective multicenter national observational descriptive study collecting data of 2nd line (L) treatments in mCRPC patients to analyze responses and progression to 1stL D. Results: 149 patients have been recruited from July 2013 to January 2015. Median age was 72 (48-89). Median D cycles was 6 (1-24), and median dose: 75 mg/m2 (30-75). 24 patients (16%) required dose reduction. The reasons for D ending were treatment completion (40%, n = 60), toxicity (15.3%, n = 23), progression (radiological, biochemical, clinical; 42%, n = 63), or others (2.7%, n = 4). 67% (n = 100) of the patients received A, 25% (n = 44) CZ, and 8% (n = 5) other treatments as 2ndL. From those who completed or progressed to D (n = 123), 2ndL initiation was mainly determined by two progression criteria (2C; biological and radiological), followed by one progression criteria (1C). This was independent of the 2ndL treatment chosen, and it was observed in similar ratios in both A (2C: 50%, n = 39; 1C: 37.2%, n = 29) and CZ (2C: 62.5%, n = 25; 1C: 27.5%, n = 11). Nevertheless, A was predominantly given when patients progressed after D ending, whereas CZ was mostly given when progressing during D (Table 1). Conclusions: A is the 2ndL treatment of choice in routine clinical practice in Spain, independent of the type and time of progression. CZ is preferentially used in patients progressing during D treatment. [Table: see text]

e15537 Background: No standard regimen exists for second line treatment of mTCC patients. Taxanes have shown some activity in this setting. Cbz, is a novel semi-synthetic taxane never tested before...

e16022 Background: Docetaxel (D) is the standard treatment for symptomatic or aggressive mCRPC. Abiraterone acetate (AA) in combination with prednisone improves OS and rPFS in mCRPC chemotherapy (CT) naive patients (pts) with asymptomatic or minimally symptomatic disease (Ryan CJ, 2013; ZYTIGA Janssen Biotech, Inc., 2012). This study aims to evaluate efficacy and safety of AA maintenance in combination with D after disease progression to first line AA in mCRPC. Methods: This is a randomized, phase II, open-label study conducted in CT naive mCRPC pts progressing after AA treatment. Pts with confirmed histologically or cytologically adenocarcinoma of the prostate, metastatic disease other than visceral, progression to previous castration, ECOG PS 0-1, testosterone < 50 ng/dL and adequate, hematologic, hepatic, and renal function were included to receive AA treatment (1000 mg qd plus prednisone 10 mg qd) until disease progression determined by PSCWG2 criteria. In a second stage pts will be randomized to rece...

TPS5073 Background: Enzalutamide (E) is a newly authorized drug for metastatic CRPC. E inhibits binding of androgens to androgen receptors, nuclear translocation of activated receptors and DNA tran...

TPS4584 Background: Metastatic or locally advanced squamous penile carcinoma (MLASPC) is an infrequent disease, with extremely bad prognosis. Platinum based chemotherapy is the most active treatmen...

e16051 Background: Ra improves survival in bone symptomatic mCRPC pts. Response assessment to Ra is difficult because of low PSA responses and pts are monitored through alkaline phosphatase (ALP) and clinically. CTCs count is a well-known predictive and prognostic biomarker in mCRPC. The aim of the study was to assess CTCs as a predictive biomarker for response to Ra therapy. Methods: Blood samples were collected from 46 pts with mCRPC treated with Ra at 8 hospitals in Spain between February and October 2014. Samples were obtained at baseline, at cycle 3 and at progression and were centrally analyzed using the CellSearch System. Statistic analysis was done with SAS v9.3 program. CTCs outcome at cycle 3 was defined as: response: decrease > 50% in relation to baseline or ≤ 5 CTCs; progression: increase > 50% or > 5 CTCs; and stabilization: absence of either response or progression. Results: We collected samples at baseline, cycle 3 and progression from 42, 32 and 18 pts respectively (see table). Pts charact...

4525 Background: Treatment of mTCC progressing to cisplatin is an unmet need. Prognostic factors (PF) for worse overall survival (OS) are ECOG >0, Hb