e16096 Background: In the past 3 years new therapies, such as cabazitaxel (C): a novel taxane, enzulatamide (E): a new androgen receptor signaling inhibitor and abiraterone acetate (A): an inhibitor of androgen synthesis, have been developed in the treatment of post-docetaxel metastatic CRPC patients. This study assessed the clinical impact of these new drugs, comparing the outcomes of two historical cohorts of patients with mCRPC. Methods: We retrospectively reviewed the data of all patients with mCRPC treated by first line chemotherapy with docetaxel (D) at the Centre Léon Bérard. Based on the timing of the development of new drugs, we defined two cohorts based on two time periods depending on drugs available on the market: group 1: 2006-2009 corresponding to the period when only conventional drugs (D, mitoxantrone) were available; group 2: 2009-2012 corresponding to the period when new drugs like C, E, A could be used post docetaxel. Outcome evaluated was overall survival (OS). OS was defined as the time from date of D introduction to date of death or date of last follow-up for patients alive at last contact. Survival distributions were estimated by the Kaplan-Meier method and compared between groups using Log-Rank test. Results: One-hundred and thirty five patients were included: 66 patients in group 1 and 69 patients in group 2. Median age was 64 years in both groups. Karnofsky score was ≥ 80% for 67.7% of patients in group 1 and 81.8% in group 2. Gleason score was ≥ 9 for 38.7% and 31.4% of patients, respectively. In group 1, 47% of patients had visceral metastases when started on chemotherapy vs 40.6% in group 2. The weekly schedule of D (25mg/m2) was significantly more frequently used in group 1 than in group 2 (53% vs 15%, p<0.001). Median cumulative doses of D at first line treatment were significantly higher in group 2: 643 mg/m2 vs 454 mg/m2 (p<0.001). Median overall survival was 10.6 months (95% CI 7.8–15.7) in group 1 vs 32.5 months (95% CI 25–42.4) in group 2 (p<0·0001). Conclusions: This study reflects how the management of mCRPC patients has evolved over the last 7 years. Survival has improved especially through an earlier management, a more intensive schedule of D and the impact of these new drugs.

282 Background: Muscle invasive urothelial cancers are infrequent. Patients (pts) with metastatic disease have poor prognosis. Brain metastases (BM) are rare. The aim of this retrospective study is to analyse the characteristics, the treatment and the evolution of patients with BM treated in a single centre. Methods: Thirty pts with BM were identified among the 1591 pts with urothelial carcinoma seen at the Centre Léon Bérard, between 1994 and 2011. The study population was described, overall survival (OS) from diagnosis of BM was estimated by Kaplan-Meier method and prognostic factors were explored using a Cox model. Results: Twenty seven pts in our series were male. Median age at initial diagnosis was 60 years (range: 33.9-78.9 years). Twenty two pts had primary bladder tumours and 8 upper urinary tract tumours. Twenty four pts underwent surgery for their primary lesion, 2 received chemoradiotherapy and 4 did not receive any radical local treatment. Six pts had metastatic disease at initial presentation: 3 were operated on. Median delay between initial diagnosis and BM was 16.6 months (range: 0-56.4 months), 3 patients had BM at initial presentation. Median time between first metastases and BM was 10 months (range=0-52 months). Eleven patients developed BM as one of the first sites of metastases. BM were symptomatic in 28 pts: specific neurological symptoms (n=25), headaches (n=6), epilepsy (n=2). For the 2 other pts, they were discovered on a systematic brain MRI. Eighteen pts had cerebral metastases only, 5 pts had cerebellar metastases only, 6 had both; the last patient had cerebral, cerebellar and meningeal involvement. Half of the pts had only 1 brain lesion. Five pts were operated on: 4 received postoperative radiotherapy; 19 patients were given radiotherapy alone and 6 did not get any local therapy. In this series, median OS from diagnosis of BM was 3.4 months (IC95% [2.2-10.3]). Only the administration of chemotherapy after the diagnosis of BM was significantly associated with OS; probably because only fit enough patients were offered treatment. Conclusions: Prognosis of patients with urothelial carcinoma and BM is poor; however some patients have long survivals. Treatment is not codified as there is little data in the literature.

e15009 Background: Muscle invasive urothelial cancers are infrequent. Patients (pts) with metastatic disease have poor prognosis. Brain metastases (BM) are rare. The aim of this retrospective study is to analyse the characteristics, the treatment and the evolution of patients with BM treated in a single centre. Methods: Thirty pts with BM were identified among the 1591 pts with urothelial carcinoma seen at the Centre Léon Bérard, between 1994 and 2011. The study population was described, overall survival (OS) from diagnosis of BM was estimated by Kaplan-Meier method and prognostic factors were explored using a Cox model. Results: Twenty seven pts in our series were male. Median age at initial diagnosis was 60 years (range: 33.9-78.9 years). Twenty two pts had primary bladder tumours and 8 upper urinary tract tumours. Twenty four pts underwent surgery for their primary lesion, 2 received chemoradiotherapy and 4 did not receive any radical local treatment. Six pts had metastatic disease at initial presentation: 3 were operated on. Median delay between initial diagnosis and BM was 16.6 months (range: 0-56.4 months), 3 patients had BM at initial presentation. Median time between first metastases and BM was 10 months (range=0-52 months). Eleven patients developed BM as one of the first sites of metastases. BM were symptomatic in 28 pts: specific neurological symptoms (n=25), headaches (n=6), epilepsy (n=2). For the 2 other pts, they were discovered on a systematic brain MRI. Eighteen pts had cerebral metastases only, 5 pts had cerebellar metastases only, 6 had both; the last patient had cerebral, cerebellar and meningeal involvement. Half of the pts had only 1 brain lesion. Five pts were operated on: 4 received postoperative radiotherapy; 19 patients were given radiotherapy alone and 6 did not get any local therapy. In this series, median OS from diagnosis of BM was 3.4 months (IC95% [2.2-10.3]). Only the administration of chemotherapy after the diagnosis of BM was significantly associated with OS; probably because only fit enough patients were offered treatment. Conclusions: Prognosis of patients with urothelial carcinoma and BM is poor; however some patients have long survivals. Treatment is not codified as there is little data in the literature.

20 Background: Metastatic castration-sensitive prostate cancer (mCSPC) primarily affects older men (OM). In this post-hoc analysis we investigated the safety and efficacy of abiraterone acetate + prednisone (AAP) in older (≥ 70 years) and younger (< 70 years) patients in PEACE-1. Methods: Men with de novo mCSPC were allocated to standard of care (SOC), SOC + AAP, SOC + radiotherapy (RXT), or SOC + AAP + RXT in this 2x2 design phase 3 trial. SOC was initially androgen deprivation therapy (ADT) alone, then from Oct 2015 onwards, the use of docetaxel (D) was authorized as part of SOC (at the investigator’s discretion until 2017, then, following the publication of LATITUDE and STAMPEDE trials, accrual was restricted to men receiving ADT+ D). Efficacy and safety in OM included in PEACE-1 were analyzed with the same methods used in the overall trial (Lancet 2022; 399: 1695-1707). Results: A total of 741 younger men (YM) (63%) and 431 OM (37%) were randomized. OM presented with more altered PS (ECOG 1-2) (36% vs 26% p=0.0003) and less frequent use of docetaxel (D) as part of SOC (66% vs 51% p<0.0001) than YM. Hypertension (56,5% vs 38,2%, p<0,001) and diabetes mellitus type 2 (15,5% vs 11%, p=0,029) were significantly more frequent in OM. Median time to AAP discontinuation was shorter (30.0 months [95%CI= 22.1; 35.4] vs 41.4 [95%CI= 31.5; 54.0] independently of D use and more frequently due to adverse events or death in the older than younger population. The benefit of AAP on radiographic progression-free survival (rPFS) tended to decrease with age in the overall population: (HR 0.65, 95%CI 0.42-1.01) in OM vs (HR 0.49, 95%CI 0.35-0.69) for YM. The same trend was observed on overall survival (OS): (HR 0.95, 95%CI 0.72-1.25) for OM vs (HR: 0.73, 95%CI 0.58-0.92) for YM. On the other hand, in men fit to receive the SOC composed of ADT+D, the rPFS benefit of AAP was comparable in OM (HR 0.55, 95%CI 0.29-1.04) and in YM (HR 0.5, 95%CI 0.33-0.78). The OS benefit of AAP was: (HR 0.80, 95%CI 0.53-1.2) and (HR 0.71, 95%CI 0.52-0.95) in OM and YM, respectively. Safety data show that severe adverse events (grade 3-5) were more frequent in OM receiving AAP in comparison with YM (69% vs 61%) while there was no difference between older and YM not receiving AAP (48% vs 47%). Conclusions: This post-hoc analysis of PEACE-1 suggests that, in the overall population, OM derive a lower benefit, both in terms of rPFS and OS, from adding AAP to SOC versus YM. This decreased benefit is likely due to more toxicity leading to more frequent and earlier drug discontinuation. Importantly, in OM fit enough to receive ADT+D, the benefit of adding AAP to SOC was comparable to YM. Clinical trial information: NCT01957436 .

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