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Bone metastases; Metastatic castration-resistant prostate cancer Metástasis óseas; Cáncer de próstata metastásico resistente a la castración Metàstasis òssies; Càncer de pròstata resistent a la castració metastàtic Purpose The paper aims to evaluate the efficacy and safety of 223Ra in patients who progressed after first-line androgen deprivation therapy. Patients and methods EXCAAPE (NCT03002220) was a multicentre, single-arm, open-label, non-controlled phase IIa trial in 52 patients with metastatic castration-resistant prostate cancer and asymptomatic bone metastases who have progressed on abiraterone acetate or enzalutamide, up to six doses of 223Ra (55 kBq/kg of body weight per month). The primary end-point was radiographic progression-free survival (rPFS). Secondary end-points included rPFS based on androgen receptor splice variant 7 (AR-V7) expression in circulating tumour cells (CTCs), overall survival, and safety. Results Median rPFS was 5.5 months (95% CI 5.3–5.5). Median rPFS of patients with AR-V7(−) CTCs was longer than that of patients with AR-V7(+) CTCs (5.5 versus 2.2 months, respectively; P = 0.056). Median overall survival was 14.8 months (95% CI 11.2–not reached) and was significantly greater for AR-V7(−) patients than for AR-V7(+) patients (14.8 months versus 3.5 months, respectively; P < 0.01). 223Ra was well tolerated; anaemia and thrombocytopenia were the most common grade 3/4 adverse events (5.8% and 11.5%, respectively). Conclusions 223Ra seems to be a reasonable treatment for patients with metastatic castration-resistant prostate cancer and asymptomatic bone metastases progressing on novel hormonal therapy and had an acceptable safety profile. The study was conceived and designed by Joan Carles in collaboration with Medica Scientia Innovation Research (MEDSIR). MEDSIR, as legal sponsor of the study, is responsible for compliance with all clinical and regulatory procedures and adherence to the study protocol. MEDSIR had a role in study design, collection, management, analysis, and interpretation of the data and writing of the report. Bayer Inc. funded the study and provided 223Ra. The funder of the study had no role in data collection, management, data analysis, data interpretation, writing of the report, or decision to submit the manuscript for publication. All authors had full access to the data used to prepare the manuscript and participated in writing, editing, and/or critically reviewing the manuscript. The manuscript was written with editorial support from a medical writer, funded by MEDSIR. The corresponding author had final responsibility for the decision to submit for publication.

Cancer patients can experience flares of pain, called breakthrough pain (BTcP), despite treatment with painkillers. Although BTcP can be excruciating, its intensity and other characteristics depend on several factors, including its treatment. However, even if treated, BTcP can impair quality of life for cancer patients. We assessed quality of life in 118 patients with advanced cancer and BTcP treated in 13 medical oncology departments across Spain. We treated BTcP with individualized therapy, taking into account both pain-related and patient-related factors. We also measured quality of life using a specific, widely-used questionnaire at the study visits: at onset of individualized pain therapy and after 3, 15 and 30 days’ treatment. At each visit, flare-up pain therapy was adjusted or maintained as necessary. Throughout the study, quality of life and sleep quality improved for all participants. Furthermore, there was a greater reduction in intensity, duration and frequency of BTcP. The most common treatments for flare-ups were low doses of rapid-onset opioids (fentanyl given by sublingual, buccal or nasal administration), which were much better tolerated than high-dose opioids. Overall, the study showed that quality of life in patients with advanced cancer and BTcP increased after individualized pain therapy, mainly with low doses of rapid-onset opioids.

The emerging role of BRAF and MEK tyrosine-kinase inhibitors has shown new opportunities of treatment for patients with advanced melanoma and BRAF mutations. Its use is associated with some toxicities, as pyrexia, that clinicians may not be familiarized with. We present the case of a patient diagnosed with stage IV melanoma BRAF Val600E mutated who was started on dabrafenib and trametinib and developed three severe episodes of fever, hypotension and acute phase reactants elevation during the first 3 months of therapy, in the absence of microbiological demonstration of infection. The episodes were initially managed as a septic shock with broad-spectrum antibiotics and vasoactive drugs, while treatment with dabrafenib and trametinib was withheld. After two subsequent dose reduction of dabrafenib, the patient did not experience new episodes of fever.

Eribulin is active and safe in heavily pre-treated metastatic breast cancer patients. Few safety data have been published in third line. We aimed to report the specific safety profile on third line beyond taxanes and anthracyclines in advanced breast cancer (ABC). A multicenter phase II, prospective study was conducted in anthracyclines and taxanes pre-treated HER2-negative ABC, programmed to receive eribulin as third-line chemotherapy. Adverse events (AEs) were assessed and classified according to CTCAE. In addition, efficacy, in terms of overall survival (OS) and progression-free survival (PFS), and the dynamics of circulating tumor cells (CTCs) during treatment were assessed. 59 patients fulfilled the criteria. All but one showed AEs with a cumulative number of 598 AEs. The most frequent grade 3/4 drug-related AEs were neutropenia (1.7%), febrile neutropenia (0.5%), leukopenia (0.5%), alopecia (0.5%), asthenia (0.3%), elevated gamma glutamyl transferase levels (0.2%), and respiratory tract infection (0.2%). Median PFS was 4 months (95% CI 3.1-5.9) and median OS was 13.6 months (11.8-not reached). The mean number of CTCs in peripheral blood was significantly reduced from baseline to cycle 2 (16.8 vs 5.4 CTCs; P < 0.001). Median OS was significantly longer in

[Background] Small cell lung cancer (SCLC) is one of the greatest therapeutic challenges of oncology. Potential associations between single nucleotide polymorphisms in heat shock protein β1 (HSPB1) and transforming growth factor β1 (TGFβ1) and survival have been investigated., [Methods] A prospective multicenter study of 94 patients with SCLC treated between 2013 and 2016 was conducted. Clinical, tumour-related, therapeutic, and genetic (9 SNPs of TGFβ1 gene and 5 of HSPB1 gene) variables were analyzed., [Results] The cohort included 77 men and 17 women with a median age of 61 years. Eighty percent presented with limited stage at diagnosis and received thoracic radiation with a median dose of 45 Gy (twice-daily radiation in 42%). Forty-seven percent received concurrent platinum-based chemotherapy and 57% received prophylactic cranial irradiation (PCI). Overall survival (OS) was 34% at 2 years and 16% at 3 years. In multivariate analysis, the rs4803455:CA genotype of the TGFβ1 gene showed a statistically significant association with lower disease-free survival (DFS; hazard ratio [HR] 3.13; confidence interval [CI] 1.19–8.17; p = 0.020) and higher local recurrence (HR 3.80; CI 1.37–10.5; p = 0.048), and a marginal association with lower OS (HR 1.94; CI 0.98–3.83; p = 0.057). A combined analysis showed that patients receiving PCI and carrying the rs4803455:CA genotype had statistically significant lower OS (p < 0.001) and DFS (p < 0.001) than patients receiving PCI and carrying the rs4803455:AA genotype., [Conclusions] Genetic analysis showed the CA genotype of TGFβ1 SNP rs4803455 was associated with worse prognosis in patients with SCLC and could be considered as a potential biomarker.

espanolIntroduccion: El objetivo de este estudio fue evaluar la percepcion de los oncologos sobre la adherencia al tratamiento con opioides para el dolor irruptivo oncologico (DIO) en la practica clinica real. El estudio tambien incluyo una evaluacion de otros aspectos del manejo del DIO, como las razones de la no adherencia, la adecuacion del tratamiento, o las posibles intervenciones necesarias para mejorar la adherencia. Metodos: Este estudio observacional multicentrico se realizo en 84 hospitales de toda Espana. Los oncologos fueron encuestados por medio de un cuestionario online sobre su manejo del dolor oncologico basal y del DIO, y su percepcion de la adherencia a los tratamientos. Resultados: Los oncologos (n = 97) indicaron que su primera opcion para el DIO fue el fentanilo (varias formulaciones), con alta tolerancia (> 76 % de los pacientes). La mayoria de los oncologos (96,8 %) evaluaron la adherencia en sus pacientes, pero solo el 69,1 % siempre prescribio medicamentos para prevenir los efectos adversos de los opioides, y solo el 74,2 % siempre titulo la dosis minima. La mayoria de los oncologos (51 %) percibieron que el 25-50 % de los pacientes no mostraban buena adherencia al tratamiento para DIO. La adherencia a los tratamientos de dolor basal fue alta, aunque muchos oncologos consideraron que los pacientes generalmente dejaban de tomar el medicamento cuando se sentian mejor. Las principales razones para la no adherencia fueron la sensacion de que el tratamiento era innecesario, la ineficacia percibida del tratamiento, la preocupacion por los posibles efectos adversos y la falta de apoyo familiar. Conclusiones: Los oncologos percibieron que la adherencia al tratamiento para el DIO puede mejorarse y recomendaron el tratamiento de los efectos adversos de la medicacion, una mejor educacion sobre el manejo del dolor a los pacientes y familiares, instrucciones escritas de prescripcion y simplificacion de los regimenes de medicamentos. EnglishObjectives: The objective of this study was to evaluate the perception of oncologists on adherence to opioid treatment for breakthrough cancer pain (BTcP) in current clinical practice. Our study also included an assessment of other aspects of the management of BTcP, such as the reasons for non-adherence, the adequacy of the treatment, or the possible interventions required to improve adherence. Methods: This observational, multicentric study was carried out in 84 hospitals throughout Spain. Oncologists were surveyed by means of an online questionnaire on their management of background cancer pain and BTcP, and their perception of adherence to the treatments. Results: Oncologists (N = 97) reported that their first choice for BTcP was fentanyl (various formulations), with high perceived tolerance (> 76 % of patients). Most oncologists (96.8 %) evaluated adherence in their patients but only 69. 1% always prescribed medication to prevent adverse effects of opioids and only 74.2 % always titrated the minimum dose. Most oncologists (51.0 %) perceived that 25-50 % of the patients did not adhere to the treatment for BTcP. Adherence to background pain treatments was high, although many oncologists considered that patients usually stopped taking the medication when feeling better. The main reported reasons for non-adherence were the self-perceived feeling that treatment was unnecessary, perceived inefficacy of the treatment, concerns about potential adverse effects, and lack of family support. Conclusions: Oncologists perceived that adherenceto BTcP treatment can be improved and recommended treatment of adverse effects, better education about pain management to patients and relatives, written prescription instructions, and simplification of drug regimens.

[Purpose] Germline mutations in DNA damage repair (DDR) genes are identified in a significant proportion of patients with metastatic prostate cancer, but the clinical implications of these genes remain unclear. This prospective multicenter cohort study evaluated the prevalence and effect of germline DDR (gDDR) mutations on metastatic castration-resistance prostate cancer (mCRPC) outcomes., [Patients and Methods] Unselected patients were enrolled at diagnosis of mCRPC and were screened for gDDR mutations in 107 genes. The primary aim was to assess the impact of ATM/BRCA1/BRCA2/PALB2 germline mutations on cause-specific survival (CSS) from diagnosis of mCRPC. Secondary aims included the association of gDDR subgroups with response outcomes for mCRPC treatments. Combined progression-free survival from the first systemic therapy (PFS) until progression on the second systemic therapy (PFS2) was also explored., [Results] We identified 68 carriers (16.2%) of 419 eligible patients, including 14 with BRCA2, eight with ATM, four with BRCA1, and none with PALB2 mutations. The study did not reach its primary end point, because the difference in CSS between ATM/BRCA1/BRCA2/PALB2 carriers and noncarriers was not statistically significant (23.3 v 33.2 months; P = .264). CSS was halved in germline BRCA2 (gBRCA2) carriers (17.4 v 33.2 months; P = .027), and gBRCA2 mutations were identified as an independent prognostic factor for CCS (hazard ratio [HR], 2.11; P = .033). Significant interactions between gBRCA2 status and treatment type (androgen signaling inhibitor v taxane therapy) were observed (CSS adjusted P = .014; PFS2 adjusted P = .005). CSS (24.0 v 17.0 months) and PFS2 (18.9 v 8.6 months) were greater in gBRCA2 carriers treated in first line with abiraterone or enzalutamide compared with taxanes. Clinical outcomes did not differ by treatment type in noncarriers., [Conclusion] gBRCA2 mutations have a deleterious impact on mCRPC outcomes that may be affected by the first line of treatment used. Determination of gBRCA2 status may be of assistance for the selection of the initial treatment in mCRPC. Nonetheless, confirmatory studies are required before these results can support a change in clinical practice., Supported by an unrestricted grant from Fundación Cris contra el cancer; three investigator awards from the Prostate Cancer Foundation (C.C.P. [2013], D.O. [2014], and E.C. [2017]); and three grants from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III (No. PI13/01287 and PI16/01565 to D.O. and No. PI15/01471 to P.L.). During the conduct of this study, E.C., D.O., P.N., and L.M.-P. were supported by grants from Ministerio de Economía, Industria y Competitividad (No. JCI-2014-19129 [E.C.], No. RYC-2015-18625 [D.O.], No. SVP-2013-067937 [P.N.], No. SVP-2014-068895 [L.M.]); D.O. was also funded by a Return fellowship from Fundación Científica de la Asociación Española Contra el Cancer, 2012-2015; N.R.L. and R.L., by grants from Instituto de Salud Carlos III (No. CM14-00200 to N.R.L. and No. CM17-00221 [R.L.]); and Y.C., by a grant from Ministerio de Educación, Cultura y Deportes (No. FPU15/05126). C.C.P. was supported by a congressional-designated medical research program award (No. CMRP-PC131820).

4577 Background: Cancer is recognized as a major risk factor for severe COVID19. However little is known about the impact of oncologic treatments in the evolution of the disease. On the other hand, the influence of SARS-CoV2 in cancer response remains to be established. We aim to determine both aspects in renal cancer patients receiving different therapeutic options. Methods: We designed a retrospective case-control study to compare the outcome of patients with advanced renal cancer who developed COVID19 under antiangiogenic treatment (cohort A [ChA]) vs immunotherapy (alone or in combination: cohort B [ChB]) vs matched controls (cohort C [ChC]). Controls were renal cancer patients who were not infected during the period of study. One control per case was selected regarding age, gender, kidney cancer histology and type of treatment. Results: From May 20 to Feb 21, 80 patients were recruited. We present the first 55 patients included (15 ChA, 16 ChB and 20 ChC, 4 patients were screening failure) from 13 centers in Spain. Median age was 62 (range 25 to 88) overall and 62 (range 44 to 88) in Ch A, 64,5 (range 42 to 83) in ChB and 61 (range 41 to 77) in ChC. 38 patients were male and 13 were female. Overall 45 cases were clear cell carcinoma (13 ChA, 14 ChB and 18 ChC), 4 papillary (1 ChA, 2 ChB and 1 ChC), 1 chromophobe (ChA) and 1 unclassified (ChC). Median number of prior lines of treatment was 2 (range 1 to 6) overall, (1 [range 1 to 4] in ChA, 2 [range 1 to 4] in ChB and 2 [range 1 to 6] in ChC). 25 patients required treatment interruptions (8 in ChA [32%], 14 in ChB [56%] and 3 [12%] in ChC). 9 patients were hospitalized (4 in Ch A, 5 in ChB and none in ChC) for a median of 10 days (range 4 to 16) overall (7 [range 4 to 14] in ChA and 12 [range 5 to 16] in ChB). No patient required ICU admission. Best tumor response was complete or partial (CR+PR) in 25 patients (5 [20%] in ChA, 9 [36%] in ChB and 11 [44%] in ChC). Clinical benefit (CR+PR+stable disease) was observed in 38 patients (11 [28,9%] in ChA, 10 [26,3%] in ChB and 17 [44,7%] in ChC). One patient in ChB died (due to COVID19). Updated results will be presented. Conclusions: Patients with renal cancer who developed COVID19 held treatment more frequently and presented lower clinical benefit rates than non infected cases. Patients receiving immunotherapy required more frequent dose interruptions and longer hospitalizations than cases on antiangiogenics. These results point to an impact of SARS-CoV2 in renal cancer outcome. Therapies administered to treat renal cancer, could play a role in the evolution of COVID19.

5554 Background: The CARD trial proved that in mCPRC patients (pts), previously treated with docetaxel and an androgen-receptor signaling inhibitor (ARSi), cabazitaxel (CBZ) significantly improves progression-free (PFS) and Overall Survival (OS) compared with the alternative ARSi. Concurrently, the PROFOUND study showed the superiority of olaparib vs. ARSi in pts with similar prior treatment history and genetic alterations in Homologus Recombination DNA repair related genes (HRR). Methods: PROREPAIR-B (NCT03075735) is a prospective study which aimed to demonstrate the prognostic role of germline deleterious mutations in (g)HRR genes and the benefit of first (1L), second (2L) and subsequent therapy lines for mCRPC. Outcomes with 1-2L have been previously reported. Here we evaluated radiographic (r)-PFS, clinical (c)-PFS, and OS in PROREPAIR-B pts who meet CARD study eligibility criteria and who received CBZ and/or ARSi. Survival analysis were performed using Kaplan Meier method and Cox regression models. Results: 95 out of 419 mCRPC pts included in PROREPAIR-B meet CARD eligibility criteria and received CBZ (n=60) or ARSi (n=35) including 14 gHRR carriers, 8/6 treated with CBZ/ARSi, respectively. Visceral metastases were more frequent among pts treated with CBZ (p=0.01). ECOG 2, M1 at diagnosis, Abiraterone as 1st ARSi and prior radiographic PD (all p

e21662 Background: Immunotherapy of cancer has changed the paradigm of treatment of many tumours, specially non-small cell lung cancer (NSCLC). The use of immune-checkpoint inhibitors (ICI) is associated in some patients with the development of new immune-related adverse events (irAEs). Our aim was to study if there is any correlation between the appearence of irAEs and the efficacy of ICI. Methods: We collected data of 104 patients diagnosed of advanced NSCLC and treated with ICI in monotherapy at our institution between December 2015 and December 2019. Several variables as clinical, tumour-related and therapeutical were included and univariate and multivariate Cox regression analysis were performed. Results: Cohort of 84 men and 20 women, median age of 67 years and 86% with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 89% were active or ex-smokers and 11% had never smoked. 60% of patients had adenocarcinoma histology, 39% scamous and 1% had not otherwise specified (NOS) carcinoma histology. 3% of patients had III-B stage at the moment of start of immunotherapy, 37% M1a, 30% M1b and 30% M1c. 2 patients had driver mutations in EGFR gene. 41% of patients had unknown PDL1 status; 14% had no PDL1 expression, 14% low expression and 31% high expression. 78% of patients had progressed to prior line of treatment, while 22% were treatment-naive. irAEs occured in 65% of patients; 12% developed grade 3 to 4 toxicities. More frequent irAEs were fatigue (54%) and rash (27%). Significant statistical variables in univariate analysis were included in multivariate analysis by Cox regression. The appearence of any grade of iRAE was associated with improved progression-free survival (PFS) (median 17.9 months vs 5.1 months; HR 7.12; p = 0.008). Those patients who experimented any grade of irAE were more likely to achieve stabilization or response than those who suffered progression of disease (HR 13.00; p < 0.001; 95% CI [3.47-48.78]. The use of corticosteroids during treatment with ICI was not related to the benefit of treatment. Conclusions: Appearence of immune-related adverse effects during treatment with ICI was associated with better outcomes in our population. The use of corticosteroids during immunotherapy didn´t have any deleterious effect on the efficacy of treatment.

e21664 Background: Hyperprogressive disease (HPD) is a new pattern of progressión during immunotherapy and is described as an acceleration of tumor growth during treatment with immune checkpoint inhibitors (ICI). The rate of HPD in advanced solid tumors remains unknown, but it has been reported in 9% to 29% of patients in two recent series. Our aim was to study prognostic factors of HPD. Methods: We collected data of 104 patients diagnosed of advanced NSCLC and treated with ICI in monotherapy at our institution between December 2015 and December 2019. Several variables as clinical, tumour-related and therapeutical were included in the analysis. The variables were compared by chi-square and Fisher test, then we performed a multivariate logistic regression model to analyse the effects of the covariates, and finally we performed a Kaplan Meier survival analysis. We described HPD as disease progression at first evaluation with an increase in tumor growth rate exceeding 50%, according to Gustave Roussy criteria previously reported. Results: Cohort of 84 men and 20 women, median age of 67 years and 86% with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 89% were active or ex-smokers and 11% had never smoked. 60% of patients had adenocarcinoma histology, 39% scamous and 1% had not otherwise specified (NOS) carcinoma histology. 3% of patients had III-B stage at the moment of start of immunotherapy, 37% M1a, 30% M1b and 30% M1c. 2 patients had driver mutations in EGFR gene. 41% of patients had unknown PDL1 status; 14% had no PDL1 expression, 14% low expression and 31% high expression. 78% of patients had progressed to prior line of treatment, while 22% were treatment-naive. Nine of 104 patients (8.7%) in our population developed HPD during treatment with ICI. HPD occured within the first two months of treatment in all 9 patients, and was associated with worse overall survival in the multivariate analysis by Cox regression (12.6 vs 2.6 months; HR 13.94, p < 0.001). The presence of 2 or more metastatic sites was related to the development of HPD in the multivariate analysis (HR 8.59, p = 0.026). Conclusions: The incidence of HPD in our population is concordant with previous report about this topic. As previously described by Ferrara et al, HPD was significantly associated with a high number of metastatic sites before start treatment with ICI and correlated with poor outcomes in patients with advanced NSCLC.

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...

247 Background: Germline DDR have been identified in up to 12% of mCRPC patients. Initial results from various retrospective series have reported discordant impact in clinical outcomes associated to these gDDR following conventional treatments. PROREPAIR-B (Castro et al ESMO 2017) is the first prospective study to address this question. In this planned sub-analysis, we report mCRPC treatment outcomes associated to taxanes. Methods: PROREPAIR-B (NCT03075735) is a prospective multicentre observational cohort study. Patients diagnosed with mCRPC, with unknown mutational status at study entry and who were going to start a first-line treatment for mCRPC were eligible. For this sub-analysis patients who received docetaxel or cabazitaxel as first-taxane were selected. The endpoints of this sub-analysis included to assess the impact of BRCA1, BRCA2, ATM and PALB2 and other gDDR on cause-specific survival (CSS), progression free survival (PFS), time to PSA progression (bPFS) and response to the first administered taxane as 1st or 2nd line therapy. Results: 326 (12 BRCA2, 8 ATM and 1 BRCA1 mutation carrier [gMUT]) out of 419 patients were eligible for this analysis. Diagnostic characteristic included Stage IV 51%, G8-10 60%. At the time of taxane initiation median PSA was 30.1 ng/mL, 84%, 48% and 11% of patients had bone, nodal and visceral metastases. CSS from first-taxane were not significantly different between gMUT and non-carriers (NC) (16.9 vs 23.2 m, p > 0.05). However, in BRCA2 carriers was significantly shorter than in NC (13.1 vs 23.3 m, p = 0.026). Despite a trend to higher PSA response rates in gMUT compared to NC (n = 288, 63% vs 42%, p = 0.07, BRCA2 55%, p > 0.05), PFS were not significantly different between both groups (7.2 vs 7.8 m, p > 0.05), with a trend to shorter survival in BRCA2 carriers (4.5 vs 7.4 m, P = 0.11). Conclusions: These results suggest that DDR mutation carriers respond to taxanes with similar time to progression compared to NC, with the exception of BRCA2 carriers, who despite to the initial response to taxanes, presented worse survival outcomes. This highlights the need for close monitoring and novel therapies in this population. Clinical trial information: NCT03075735.

623 Background: Treatment of mRC is not affected by gender, studying possible differences in a real-world study, could increase the knowledge of toxicity and possible prognostic factors. Methods: SPAZO2 (NCT03091465) was a retrospective real-world study to analyze the effectiveness of 1st-line pazopanib and subsequent therapies in mRC. Data from 530 pt treated outside CT were collected in 50 spanish centers, and externally monitored. Ineligibility criteria: ECOG > 1, pure nonclear-cell, Hgb < 9 g/dl, renal failure, severe cardiovascular disease, chronic liver disease, or recent neoplasia Results: 530 pt were included, 67.2% men (M), mean age was 66.2 years (26-92). There were no significant differences (M vs W) in the age > 75 (24.7 vs 24.1%), clear cell carcinoma (77.2 vs 79.9%), nephrectomy (72.5 vs 68.4%), IMDC (favourable: 15.2 vs 12.1%, intermediate: 59.3 vs 64.4%, poor: 25.6 vs 23.6%), metastases (lymph nodes: 46.1 vs 43.1%, lung: 69,7 vs 67,2 %, liver: 16 vs 20.1%, bone: 27 vs 24.1%, skin/soft tissues: 1.1 vs 3,4% and CNS: 4,8% vs 6.3%). Discontinuation due to toxicity or comorbidities was 12.4 vs 9.8%. There were no differences in the second lines received (57.9 vs 56.9%), neither response, PFS and OS (table). Median follow up was 39 mo. The gender has no prognostic value when adjusted for the prognostic groups of IMDC (HR of PFS 0.96, CI 95% 0.78-1.2, HR of OS: 0.92, CI 95% 0.72-1.14). Only diarrhea and elevation of uric acid were higher in the men group. Conclusions: Pazopanib was safe and effective in both groups with similar outcome. Women had less diarrhea and less increased uric acid. There were not differences in OS or PFS. In IMDC subgroup analysis, there is a trend towards a better evolution or PFS in the poor prognosis women subgroup. Clinical trial information: NCT03091465. [Table: see text]

The purpose of this study was to investigate the efficacy and safety of combination chemotherapy using estramustine and vinorelbine in chemotherapy-naive patients with hormone-resistant prostate cancer (HRPC). The patients (n = 54) received oral estramustine 840 mg/day on Days 1 to 14 and IV vinorelbine 25 mg/m2 on Days 1 and 8 of every 3 wk cycle. The median number of cycles per patient was 9 (range, 1 to 27). Fifty-three patients were evaluable for toxicity and survival and 52 for prostate specific antigen (PSA) response. Median age was 68 (range, 46–80). PSA sustained decrease >50% was seen in 52% of patients (95% CI: 38–66%). A complete response was seen in 3 and a partial response in 12 of 25 patients with measurable disease, for an overall objective response of 60% (95% CI: 41–79%). Improvement in performance status was observed in 30 out of 43 evaluable for clinical benefit response. The median duration of response was 7 mo and median time to progression was 6 mo. The median survival time was 15 mo. The most common adverse event was mild gastrointestinal toxicity. In general, toxicity G3–4 was low: granulocytopenia Grade 3–4 (8%), thrombocytopenia Grade 3 (6%), and anemia Grade 3 (13%). Other Grade 3 toxicities included deep vein thrombosis (4%), hepatic (2%), cardiac ischemia (2%), fatigue (6%), and sensory neuropathy (2%). There were 2 treatment-related deaths (4%). We conclude that vinorelbine and estramustine as used in this trial is an efficacious and well-tolerated therapeutic regimen in the management of HRPC.

In this multicenter phase II study the efficacy and safety of the alternating schedule of irinotecan (CPT-11) with bolus 5-fluorouracil (5-FU) and leucovorin (LV) were assessed as first-line chemotherapy in patients with metastatic colorectal cancer (CRC). Enrolled in the study were 43 patients with advanced CRC. They received CPT-11 350 mg/m2 i.v. on day 1, alternating with LV 20 mg/m2 i.v. and 5-FU 425 mg/m2 i.v. daily for five consecutive days, on days 22–26 (Mayo Clinic regimen). One cycle consisted of 6 weeks. A total of 179 cycles were administered with a median of four per patient (range one to nine). Efficacy was analyzed on an intention-to-treat basis. The overall objective response rate was 30% (95% CI 16–44), with four complete responses and nine partial responses, whereas 20 patients (4%) showed stable disease. The median time to disease progression was 9.0 months and median survival was 18.5 months. Grade 3/4 diarrhea was mainly related to CPT-11 rather than to 5-FU (9.3% vs 4.7% of patients), whereas grade 3/4 neutropenia was higher during 5-FU administration (16.3% vs 7.0% of patients). The alternating schedule of CPT-11 with 5 days bolus of 5-FU and low-dose LV showed a clinical benefit in terms of tumor growth control as first-line treatment of patients with metastatic CRC. The overall safety data confirmed this alternating combination as a well-tolerated treatment.

e602 Background: The clinical experience with CBZ in mCRPC patients (pts) has enriched notably since its approval for clinical use, but there is still a lack of well-defined prognostic/predictive factors to better characterize the profile of pts that could achieve the best therapeutic benefit. Analysis of the final expanded cohort and mature long-term follow-up are presented. Methods: Medical records from mCRPC pts progressing during or after docetaxel and treated with CBZ at 21 centres in Spain were reviewed retrospectively. Baseline characteristics, overall survival (OS), radiographic progression-free survival (rPFS), and toxicity were collected. Univariate and multivariate analysis of a variety of factors predicting OS were conducted. Results: 187 consecutive pts (median age 69) with intermediate-poor prognostic baseline characteristics (Table 1) received a median of 6 cycles (range 2-59) of CBZ. Median OS from first CBZ cycle was 15.3 [CI: 11.7; 18.0] months (mo) and median clinical and/or rPFS was 7.9 mo [CI: 6.8; 10.3]. Gleason score (GS) < 8 (vs ≥ 8), time under first-line androgen deprivation therapy (ADT) ( > 16.1 (median) vs < 16.1 mo) and the number of chemotherapy lines before CBZ did not significantly influence OS. Median follow-up was 9.5 mo. Febrile neutropenia occurred in 4 pts and 1 pt had neutropenic infection. Main nonhematologic grade ≥ 3 toxicities were asthenia (2.7%) and diarrhea (1.6%). Alopecia, nails disorders and peripheral neuropathy were uncommon. Conclusions: CBZ administered in the daily clinical practice is associated with consistent OS, similar to that observed in pivotal clinical trials. GS, median time under first-line ADT and number of chemotherapy lines before CBZ did not influence clinical benefit. CBZ has an acceptable safety profile. Funding: Sanofi [Table: see text]

267 Background: Optimal sequencing of new androgen-receptor targeted agents (ART) abiraterone and enzalutamide with docetaxel (DOC) and cabazitaxel (CABA) is unknown. In this large retrospective cohort of mCRPC patients (pts) treated with CABA after docetaxel (DOC), we evaluated the impact of 3 different sequences: DOC → CABA (group 1, n = 267) Or DOC → ART → CABA (group 2, n = 183) Or DOC → CABA → ART (group 3, n = 124). Methods: Records of 574 consecutive mCRPC patients were retrospectively collected in 44 centres in 6 European countries (France, Spain, UK, Greece, Poland, Turkey) from August 2012 to July 2016. Disease history and clinical characteristics at initiation of DOC therapy and outcomes were collected. Factors influencing OS were evaluated using multivariate stepwise logistic regression. Results: At DOC initiation, median age was 67 years, 83% of pts were ECOG 0-1, 45.1% had pain and 10.8% had visceral metastases. Median number of DOC cycles was 7 (6 in group 2, 7 in groups 1 and 3). Median number of CABA cycles was 6 (6 in groups 1 and 2, 7 in group 3). Median duration of ART treatment was 5.9 and 4.4 mths in groups 2 and 3, retrospectively. Median OS from first DOC cycle were 30.1, 37.1 and 40.1 mths in groups 1, 2 and 3, respectively. Factors influencing OS are summarized in the table below. Conclusions: Results of this retrospective cohort suggest that patients receiving DOC → CAB → ART show the greatest OS. High baseline PSA, short response to first-ADT and clinical progression of pts are major prognostic factors of OS at DOC initiation. The window of opportunity for chemotherapy should not be missed. [Table: see text]

751 Background: In the VELOUR trial, adding Z to FOLFIRI improves OS, PFS and RR in mCRC pts progressing after oxaliplatin ±biologic agents. The ASQoP trial (NCT01571284) was designed to gather safety and QoL data from mCRC in real-life setting. We report data collected by the Spanish investigators. Methods: ASQoP is single-arm, open-label trial evaluating safety and QoL of Z in mCRC pts as 2nd line. Eligible pts received Z (4mg/kg) q2wks on day 1/cycle, followed by FOLFIRI (dosing was at physician’s discretion) until disease progression, unacceptable toxicity, death, or investigator/pt decision. The EQ-5D was used for utility index (UI) measure and the EORTC QLQ-C30 as generic cancer instrument. QoL population consisted of pts completing the questionnaire at baseline and ≥1 assessment post-baseline and received ≥1 part of 1 dose of study treatment. Results: The safety population comprised 77 pts with ≥1 completed cycle of treatment. Grade (G)3/4 AEs were reported in 72.7% of pts (vs 83.5% in VELOUR), being G3 most commonly reported. There was no G4 hypertension, stomatitis, or proteinuria. G4 Diarrhea was found in 1.3% of pts. Mean baseline UI was 0.7 (95% CI, 0.63-0.78) in 51 pts, and remained relatively stable at cycles 3 (n=39) and 7 (n=24), with a mean (±SD) change from baseline of 0.03 (±0.26) and -0.06 (±0.35), respectively. Mean baseline global health status score was 63.1 (95% CI, 55.8-70.4) in 54 pts, and remained stable up to cycle 9 with a mean (±SD) change from baseline of 4.17 (±38). Conclusions: Thisanalysis has identified no new safety signals and suggests an acceptable toxicity profile with a relatively stable UI and QoL in Spanish mCRC pts in the real-life setting. [Table: see text]

e12504Background: Since metastatic breast cancer (MBC) is incurable, main goals of chemotherapy (CT) are the recovery and maintenance of patient health-related quality of life (HRQOL), the reduction of symptoms related with the disease and prolonging life. In this context, time to definitive deterioration (TDD) has been proposed as a modality of longitudinal HRQOL analysis for cancer patients. To date, few studies have focused in the analysis of TDD in patients with MBC treated with 2nd-line CT in a context of normal medical practice. Methods: A prospective observational study performed in 87 MBC patients (100 patients recruited; 50% of total planned) who initiated 2nd-line monoCT in 30 Spanish hospitals. Using the EORTC-QLQ-C30 questionnaire, the breast module QLQ-BR23 and the CT-induced peripheral neuropathy (CIPN) module, HRQOL was assessed at the beginning of CT and every three months thereafter until disease progression and/or treatment (TX) discontinuation. TDD was considered when HRQOL decrease 5% ...

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]

Cancer pain should be controlled in most patients, however this is not always achieved. These guidelines describe the classification, evaluation and treatment of chronic cancer pain in accordance with the WHO treatment strategy of pain stages: mild, moderate and severe. For treatment during the third stage, we cover titration and rotation of opioids, as well as their side effects and prevention. Also described is neuropathic pain and refractory pain, coadjuvant treatments and non pharmacological analgesic treatments. Finally, treatment of breakthrough pain is defined.

New advances in the diagnosis and treatment of cancer and the increased incidence and prevalence of this disease have led to an increase in the number and duration of visits in Medical Oncology in the last few years. Based on the functions of a medical oncologist and the time recommended for each work activity established by the Spanish Society of Medical Oncology (SEOM), we carried out a pilot study on the three most frequent neoplasias in our country [breast cancer (BC), lung cancer (LC) and colorectal cancer (CRC)], in order to determine the real time each patient requires from a physician and thus establish a recommendation on the number of medical oncologists necessary. Using the actual itinerary of the first 20 patients of 2009 in each of the three neoplasias seen at the Medical Oncology Service of the Virgen de Valme University Hospital, we measured the number of visits, the antineoplastic treatments received, the number of hospital admissions and average length of stay. During the years following the study, these data were estimated based on the natural history of each neoplasia. During the first year, the average time spent by the medical oncologist was 235, 390 and 265 min on each outpatient with BC, LC and CRC, respectively. In hospitalisation, the average oncologist/patient minutes were 40, 360 and 118 for BC, LC and CRC, respectively. Finally, the time spent on each visit or day of hospitalisation was that recommended by the SEOM, achieving an ultimate ratio of 1 oncologist for every 83 first visits.

Anti-angiogenic therapy benefits many patients with advanced renal cell carcinoma (RCC), but there is still a need for predictive markers that help in selecting the best therapy for individual patients. MicroRNAs (miRNAs) regulate cancer cell behavior and may be attractive biomarkers for prognosis and prediction of response. Forty-four patients with RCC were recruited into this observational prospective study conducted in nine Spanish institutions. Peripheral blood samples were taken before initiation of therapy and 14 days later in patients receiving first-line therapy with sunitinib for advanced RCC. miRNA expression in peripheral blood was assessed using microarrays and L2 boosting was applied to filtered miRNA expression data. Several models predicting poor and prolonged response to sunitinib were constructed and evaluated by binary logistic regression. Blood samples from 38 patients and 287 miRNAs were evaluated. Twenty-eight miRNAs of the 287 were related to poor response and 23 of the 287 were related to prolonged response to sunitinib treatment. Predictive models identified populations with differences in the established end points. In the poor response group, median time to progression was 3.5 months and the overall survival was 8.5, whereas in the prolonged response group these values were 24 and 29.5 months, respectively. Ontology analyses pointed out to cancer-related pathways, such angiogenesis and apoptosis. miRNA expression signatures, measured in peripheral blood, may stratify patients with advanced RCC according to their response to first-line therapy with sunitinib, improving diagnostic accuracy. After proper validation, these signatures could be used to tailor therapy in this setting.

590 Background: Polymorphisms in cytochrome P450 2D6 gene affect the plasma concentration of tamoxifen active metabolites (endoxifen). Some drugs are known to be CYP2D6 inhibitors. We aim to determine the relationship between CYP2D6*4 polymorphisms, concomitant CYP2D6 inhibitors use and clinical outcomes of breast cancer patients receiving adjuvant tamoxifen (TAM). Patients and Methods: CYP2D6*4 (1934 G>A+1) genotype was determinated from DNA of blood samples using PCR-RFLP technique and Taqman Allelic Discrimination Assay in a series of 84 breast cancer patients receiving adjuvant TAM. CYP2D6 inhibitors were recorded. Chi-square test and logistic regression models were used to determinate association between genotype, use of concomitant CYP2D6 inhibitors and disease relapse rate. Results: In our 84 patients series mean age was 51.5y. (33–71). 14.8% were stage I, 58.0% stage II and 27.2% stage III. 61.4% were nodes positive and 98.7% tumors had positive hormonal receptors. We observed disease recurrence in 36.9% of cases. The mean following-up was 5.5 y. Genotype frequency was: wt/wt (57.1%), wt/*4 (40.5%) and *4/*4 (2.4%). 50% (18 of 36) of patients with the wt/*4 + *4/*4 genotypes had disease relapse compared with 27% (13 of 48) with wt/wt genotype (P= 0.041). Only 6 patients received concomitants CYP2D6 inhibitors, mainly antidepressants, all of them with the wt/*4 genotype. 50% presented disease relapse. Clinical pathological variables were evaluated and significant relation was found between stage and disease relapse by univariate analysis (P= 0.001). We investigated whether CYP2D6*4 genotype and stage to diagnosis could influence in disease relapse. For these analyses we use as reference group the genotype wt/wt. We observed that combined genotype wt/*4 + *4/*4 was more strongly associated with disease recurrence than wt/wt genotype (adjusted hazard ratio [HR], 2.82, 95% confidence interval [CI] 1.0- 7.9) P= 0.049. Conclusions: Breast cancer patients with the CYP2D6 *4/*4 or wt/*4 genotype could have lower benefit of TAM adjuvant treatment and tend to have a higher risk of disease relapse. Pre-treatment CYP2D6 genotype determination from blood sample could predicts TAM clinical outcomes and help to oncologist in treatment decision. No significant financial relationships to disclose.

779 Background: The combination of E and T has demonstrated clinical objective response rates (ORR) up to 81% as neoadjuvant therapy for operable BC. Dose-dense chemotherapy may achieve superior cl...

736 Background: Dose-dense chemotherapy may achieve superior clinical outcomes over conventionally administered chemotherapy in BC. The primary objective of this study was to evaluate the RR of biweekly T plus E in LABC (stage III). Secondary objectives were to determine pathological response rate, safety profile and the correlation between the expression of molecular markers (MM) and response. Methods: Patients with histologically or cytologically confirmed LABC, age ≥ 18 years, ECOG PS ≤ 2 and adequate bone marrow, hepatic, renal and cardiac functions were eligible. Prior chemotherapy, hormonal therapy or radiotherapy was not allowed. Patients with invasive bilateral BC were excluded. Treatment: E (75 mg/m2) and T (75 mg/m2) iv, every 14 days with G-CSF support for 6 cycles. Surgery was recommended 3–6 weeks after completion of chemotherapy. The expression of MM, such as ER, PR, HER-2 was assessed and correlated with clinical and pathological responses. Results: To date, 48 patients have been included. ...