Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol.
Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival.
We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0-2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544).
Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86-107) in the abiraterone trial and 72 months (61-74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8-86·9) in the abiraterone group versus 45·7 months (41·6-52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53-0·73]; p<0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9-81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3-59·0) in the standard of care group (HR 0·65 [0·55-0·77]; p<0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83-1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3-5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial).
Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years.
Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.
Attard G
，Murphy L
，Clarke NW
，Sachdeva A
，Jones C
，Hoyle A
，Cross W
，Jones RJ
，Parker CC
，Gillessen S
，Cook A
，Brawley C
，Gilson C
，Rush H
，Abdel-Aty H
，Amos CL
，Murphy C
，Chowdhury S
，Malik Z
，Russell JM
，Parkar N
，Pugh C
，Diaz-Montana C
，Pezaro C
，Grant W
，Saxby H
，Pedley I
，O'Sullivan JM
，Birtle A
，Gale J
，Srihari N
，Thomas C
，Tanguay J
，Wagstaff J
，Das P
，Gray E
，Alzouebi M
，Parikh O
，Robinson A
，Montazeri AH
，Wylie J
，Zarkar A
，Cathomas R
，Brown MD
，Jain Y
，Dearnaley DP
，Mason MD
，Gilbert D
，Langley RE
，Millman R
，Matheson D
，Sydes MR
，Brown LC
，Parmar MKB
，James ND
，STAMPEDE investigators
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Real-World Treatment Patterns in Patients With Metastatic Castration-Resistant Prostate Cancer in Greece: The PROSPECT Study.
Real-world data on management of metastatic castration resistant prostate cancer (mCRPC) with novel therapies is sparse. The aim of this study was to capture real-world management strategies in patients with mCRPC who initiated first line (1L) systemic therapy with chemotherapy or novel hormonal agents (NHAs) in Greece and describe the therapeutic sequencing strategy among patients who advanced to 2L and 3L treatment.
In this noninterventional, multicentre, retrospective study (PROSPECT), a medical chart review of 149 patients with mCRPC who initiated 1L systemic therapy with chemotherapy or NHAs in 7 major anticancer hospital clinics, from public, academic, and private sectors in Greece was conducted. All endpoints were descriptively analysed. Kaplan-Meier was used for time-to-event outcomes.
At 1L (N = 149), most (78.5%) patients received NHAs; enzalutamide (52.3%), and abiraterone (26.2%). At 2L (N = 68), most (72.1%) patients received chemotherapy, most frequently docetaxel (50.0% of all patients). At 3L (N = 32), 56.3% and 31.3% of patients received chemotherapy and NHAs, respectively. Regarding treatment sequencing from 1L→2L (N = 68), most patients (55.9%) advanced from NHA→chemotherapy. Regarding treatment sequencing from 1L→2L→3L (N = 32), 34.4% advanced from NHAs→chemotherapy→chemotherapy and 31.3% from NHAs→chemotherapy→NHA. Estimated median times spent on treatment at 1L, 2L, and 3L were 9.8, 4.4, and 3.7 months, respectively.
Most patients were treated with 1L NHAs, in accordance to established guidelines (which suggest both NHA and chemo as preferred 1st line options). There appeared to be a longer time on treatment of NHAs at 1L than chemotherapy, suggesting an unmet need for treatment optimisation/recommendations for 2L and 3L treatment in mCRPC.
Liontos M
，Bournakis E
，Bournakis A
，Kostouros E
，Zolota V
，Papatheodoridi AP
，Karalis K
，Kyriazoglou A
，Zakopoulou R
，Vasili E
，Tzovaras A
，Dimitriadis I
，Emmanouil G
，Mauri D
，Christodoulou C
，Tsiatas M
，Zagouri F
，Bamias A
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Docetaxel Versus Androgen-Receptor Signaling Inhibitors (ARSI) as Second-Line Therapy After Failure of First-Line Alternative ARSI for the Elderly ≥ 75 Years Old With Metastatic Castration-Resistant Prostate Cancer (mCRPC): A SPARTACUSS-Meet-URO 26 Real-W
Androgen receptor signalling inhibitors (ARSIs) abiraterone acetate (AA) enzalutamide (Enza), are currently the standard first-line (L1) treatments for metastatic castration-resistant prostate cancer (mCRPC), and docetaxel (D) is reserved as second-line (L2) after ARSI failure. Nonetheless, D use in men ≥ 75 years old is restricted owing to treatment toxicities and patient comorbidities, and a L2 alternative ARSI is frequently used. We aimed to evaluate real-life survival and toxicity outcomes of these elderly patients after failure of L1 ARSI treatment.
We retrospectively evaluated efficacy and safety in a real-world international cohort of consecutive patients ≥ 75 years old when starting L1 ARSI for mCRPC according to the choice of L2 treatment (D versus alternative ARSI).
Of the 122 identified patients, 57 (46.7%) had received L2 ARSI and 65 (53.3%) L2 D. No difference was found in the L1 overall survival (OS) for the ARSI and D groups (32.8 vs. 30.0 months, respectively; Hazard ratio [HR] = 1.22; 95% CI, 0.77-1.95; P = .40) or in the L2 OS (18.5 vs. 17.8 months, respectively; HR = 1.09; 95% CI, 0.69-1.74; P = .71). No difference was observed for rPFS from L2 (P = .12), although a trend was observed for a numerically improved rPFS on D.
Within the limitations of a retrospective design and small population, our study suggests that D or ARSI after failure of L1 alternative ARSI are clinically comparable L2 options for elderly patients with mCRPC.
Patrikidou A
，Saieva C
，Lee-Ying R
，Nuzzo PV
，Zarif TE
，McClure H
，Davidsohn M
，Eid M
，Spinelli GP
，Catalano F
，Cremante M
，Fotia G
，Rossetti S
，Valenca L
，Vauchier C
，Ottanelli C
，Andrade L
，Gennusa V
，Mestre RP
，Fornarini G
，Pignata S
，Procopio G
，Santini D
，Ravi P
，Sweeney C
，Heng D
，De Giorgi U
，Fizazi K
，Russo A
，Francini E
，SPARTACUSS Group
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