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 (2023)

Posted on August 3, 2023 by Jason Curtis

Type of publication:
Journal article

Author(s):
Attard, Gerhardt; Murphy, Laura; Clarke, Noel W; Sachdeva, Ashwin; Jones, Craig; Hoyle, Alex; Cross, William; Jones, Robert J; Parker, Christopher C; Gillessen, Silke; Cook, Adrian; Brawley, Chris; Gilson, Clare; Rush, Hannah; Abdel-Aty, Hoda; Amos, Claire L; Murphy, Claire; Chowdhury, Simon; Malik, Zafar; Russell, J Martin; Parkar, Nazia; Pugh, Cheryl; Diaz-Montana, Carlos; Pezaro, Carmel; Grant, Warren; Saxby, Helen; Pedley, Ian; O'Sullivan, Joe M; Birtle, Alison; Gale, Joanna; *Srihari, Narayanan; Thomas, Carys; Tanguay, Jacob; Wagstaff, John; Das, Prantik; Gray, Emma; Alzouebi, Mymoona; Parikh, Omi; Robinson, Angus; Montazeri, Amir H; Wylie, James; Zarkar, Anjali; Cathomas, Richard; Brown, Michael D; Jain, Yatin; Dearnaley, David P; Mason, Malcolm D; Gilbert, Duncan; Langley, Ruth E; Millman, Robin; Matheson, David; Sydes, Matthew R; Brown, Louise C; Parmar, Mahesh K B; James, Nicholas D.

Citation:
Lancet Oncology. 24(5):443-456, 2023 May.

Abstract:
BACKGROUND: 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. METHODS: 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). FINDINGS: 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). INTERPRETATION: 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.

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MYC/BCL6 Double Hit Lymphoma Negative For (3;8) BCL6:MYC Fusion is Associated With Inferior Survival, in Contrast with T(3;8) Positive Pseudo-Double Hit Lymphoma (2023)

Posted on July 31, 2023 by Jason Curtis

Type of publication:
Conference abstract

Author(s):
Maybury, B. D.; James, L.; Chadderton, N.; Dowds, J.; Venkatadasari, I.; Riley, J.; Qureshi, I.; Talbot, G.; Giles, H. V.; Phillips, N. J.; Gonzalez, M. Vega; Rakesh, P.; Haslam, A.; Davies, D.; Moosai, S.; Lane, S. A.; *Shenouda, A.; Cherian, G. V.; Kaudlay, P. K.;Starczynski, J.; et al

Citation:
Hematological Oncology, June 2023 Supplement 1; 41: 205-207.

Abstract:

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The SSS revolution in fungal diagnostics: speed, simplicity and sensitivity (2023)

Posted on July 21, 2023 by Jason Curtis

Type of publication:
Journal article

Author(s):
*Baker, Jacob; Denning, David W.

Citation:
British Medical Bulletin. 147(1):62-78, 2023 Sep 12.

Abstract:
INTRODUCTION: Fungal disease has historically presented a diagnostic challenge due to its often non-specific clinical presentations, relative infrequency and reliance on insensitive and time-intensive fungal culture. SOURCES OF DATA: We present the recent developments in fungal diagnostics in the fields of serological and molecular diagnosis for the most clinically relevant pathogens; developments that have the potential to revolutionize fungal diagnosis through improvements in speed, simplicity and sensitivity. We have drawn on a body of evidence including recent studies and reviews demonstrating the effectiveness of antigen and antibody detection and polymerase chain reaction (PCR) in patients with and without concurrent human immunodeficiency virus infection. AREAS OF AGREEMENT: This includes recently developed fungal lateral flow assays, which have a low cost and operator skill requirement that give them great applicability to low-resource settings. Antigen detection for Cryptococcus, Histoplasma and Aspergillus spp. are much more sensitive than culture. PCR for Candida spp., Aspergillus spp., Mucorales and Pneumocystis jirovecii is more sensitive than culture and usually faster. AREAS OF CONTROVERSY: Effort must be made to utilize recent developments in fungal diagnostics in clinical settings outside of specialist centres and integrate their use into standard medical practice. Given the clinical similarities of the conditions and frequent co-infection, further study is required into the use of serological and molecular fungal tests, particularly in patients being treated for tuberculosis. GROWING POINTS: Further study is needed to clarify the utility of these tests in low-resource settings confounded by a high prevalence of tuberculosis. AREAS TIMELY FOR DEVELOPING RESEARCH: The diagnostic utility of these tests may require revision of laboratory work flows, care pathways and clinical and lab coordination, especially for any facility caring for the immunosuppressed, critically ill or those with chronic chest conditions, in whom fungal disease is common and underappreciated.

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Correlative effect between sac regression and clinical outcomes following endovascular repair in abdominal aortic aneurysm: fact or myth? (2023)

Posted on July 20, 2023 by Jason Curtis

Type of publication:
Journal article

Author(s):
Al-Tawil, Mohammed; Muscogliati, Eduardo; Jubouri, Matti; Saha, Priyanshu; *Patel, Ravi; Mohammed, Idhrees; Bailey, Damian M; Williams, Ian M; Bashir, Mohamad

Citation:
Expert Review of Medical Devices. 1-8, 2023 Jun 16

Abstract:
INTRODUCTION: Endovascular aneurysm repair (EVAR) has rapidly become the preferred management of abdominal aortic aneurysm (AAA). Sac regression status post-EVAR has been linked to clinical outcomes as well as the choice of EVAR device. The aim of this narrative review is to investigate the relationship between sac regression and clinical outcomes post-EVAR in AAA. Another aim is to compare sac regression achieved with the main EVAR devices. AREAS COVERED: We carried out a comprehensive literature search on multiple electronic databases. Sac regression was usually defined as a decrease in the sac diameter (>10 mm) over follow-up. This revealed that individuals who had sac regression post-EVAR had significantly lower mortality, and higher event-free survival rates. Further, lower rates of endoleak and reintervention were observed in patients with regressing aneurysm sacs. Sac regression patients also had significantly lower odds of rupture compared to counterparts with stable or expanded sacs. The choice of EVAR device was also shown to impact regression, with the Fenestrated Anaconda showing favorable results. EXPERT OPINION: Sac regression post-EVAR in AAA is an important prognostic factor as it translates to improved mortality and morbidity. Therefore, this relationship must be seriously taken into consideration during follow-up.

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Cardiovascular disease morbidity is associated with social deprivation in subjects with familial hypercholesterolaemia (FH): a study comparing FH individuals in UK primary care and the UK Simon Broome register linked with secondary care records (2022)

Posted on July 19, 2023 by Jason Curtis

Type of publication:
Conference abstract

Author(s):
Iyen B.; Qureshi N.; Roderick P.; *Capps N.; Durrington P.N.; McDowell I.F.W.; Cegla J.; Soran H.; Schofield J.; Neil H.A.W.; Kai J.; Weng S.; Humphries S.E.

Citation:
Atherosclerosis Plus. Conference: HEART UK 35th Annual Medical & Scientific Conference. Virtual. 49(Supplement 1) (pp S4-S5), 2022. Date of Publication: October 2022

Abstract:
Background: Measures of social deprivation are associated with higher cardiovascular diseases (CVD) morbidity and mortality. To determine if this is also seen in subjects with Familial Hypercholesterolaemia (FH), CVD morbidity has been examined in participants in the UK primary care database (CPRD) and in the UK Simon Broome (SB) register using linkage to the UK secondary care Hospital Episodes Statistics (HES). Method(s): A composite CVD outcome was analysed (first HES outcome of coronary heart disease, myocardial infarction, stable or unstable angina, stroke, TIA, PVD, heart failure, PCI and CABG). The measure of socio-economic status/deprivation used was the English index of multiple deprivation (IMD). Cox proportional hazards regression estimated hazards ratios (HR) for incident CVD and mortality [95% CI] in each IMD quintile. <br/>Result(s): We identified 4,309 patients with FH in UK CPRD primary care database (followed from 1988 to 2020), free from CVD, and 2988 SB register participants, with linked secondary care HES records. In both groups, the prevalence of FH was considerably lower in the most deprived quintile (60% in CPRD and 52% in SB). CPRD patients in the most deprived quintile (IMD-5) had the highest prevalence of obesity and of smoking compared to those from IMD quintiles 1,2,3 and 4 (p-value for trend, all <0.001). Compared to least deprived, the most deprived individuals had the highest risk of composite CVD (unadjusted HR 1.71 [CI 1.22-2.40]), however, on adjustment for smoking and alcohol consumption, there were no statistical differences in CVD risk between socio-economic groups. In the FH Register patients there was an increase in the incidence rates and hazards ratios for composite CVD with increasing quintiles of deprivation. After adjustment for age, sex, smoking and alcohol consumption, this effect remained statistically significant (quintile 5 vs 1, HR = 1.83 [1.54-2.17]. Conclusion(s): Patients with FH are underdiagnosed in lower socio-economic groups. In both CPRD and the SB Register the most deprived FH patients had the highest risk of CVD and mortality, but in CPRD but not in the SB register this was largely explained by smoking and alcohol consumption. Clinicians should adopt more effective strategies to detect FH in lower socio-economic groups, and to optimise risk factor management and to support lifestyle changes and medication adherence for this group.

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Home for Christmas MADE 3 of 3 RSH (2023)

Posted on July 7, 2023 by Jason Curtis