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Lung cancer is the most common cancer in males and the second most common among females both in Europe and worldwide. Moreover, lung cancer is the leading cause of death due to cancer in males. The European region accounts for 23% of total cancer cases and 20% of cancer-related deaths. Relationships have been described between a number of infectious agents and cancers, but our knowledge of the role of viruses, both respiratory and systemic, in the pathogenesis of lung cancer is still rudimentary and has been poorly disseminated. In this chapter, we review the available evidence on the involvement of HPV, Epstein-Barr virus, HIV, cytomegalovirus and measles virus in the epidemiology and pathogenesis of lung cancer.Copyright © ERS 2021.
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Background/Aims Immunocompromised patients have a reduced ability to generate antibodies after COVID-19 vaccination, and are at a high risk of SARSPOSTERS CoV-2 infection, complications and mortality. Tixagevimab/Cilgavimab (Evusheld) is a combination of two monoclonal antibodies which bind to the SARS-CoV-2 spike protein, preventing the virus entering human cells. Tixagevimab/Cilgavimab has been approved as COVID-19 prophylaxis for immunocompromised individuals, and is being used in over 32 different countries. The phase III PROVENT clinical trial found that high-risk participants prophylactically administered Tixagevimab/Cilgavimab had a significantly reduced risk of COVID- 19 infection after three and six months compared to controls. However, the PROVENT trial was conducted prior to the SARS-CoV- 2 Omicron wave, and did not include participants who had been previously vaccinated or infected. This systematic review provides an updated summary of the real-world clinical evidence of the efficacy of Tixagevimab/Cilgavimab for immunocompromised patients. The review reports breakthrough COVID-19 infections as its primary outcome. COVID-19-related hospitalisations, ITU admissions and mortality were included as secondary outcomes. Methods Two independent reviewers conducted electronic searches of PubMed and Medxriv, on 03/08/22 and 01/10/22. Clinical studies which reported the primary outcome of breakthrough COVID-19 infections after Tixagevimab/Cilgavimab administration were included. Clinical effectiveness was determined using the case-control clinical effectiveness methodology. Odds ratios and 95% confidence intervals (CI) between intervention and control groups were also calculated. The GRADE tool was used to assess the level of certainty for the primary outcome. Results 17 clinical studies were included in the review, with a total of 24,773 immunocompromised participants from across the world, of whom 10,775 received Tixagevimab/Cilgavimab. One randomised controlled trial, ten retrospective cohort studies (two of which were preprints) and six prospective cohort studies (one preprint) were included. The majority of studies reported clinical outcomes during the SARS-CoV-2 Omicron wave. Six studies compared a Tixagevimab/Cilgavimab intervention group to a control group. Reasons for participant immunocompromise included rheumatology patients treated with immunosuppressant drugs, transplant recipients and those with malignancies. Overall, the clinical effectiveness of prophylactic Tixagevimab/Cilgavimab against COVID- 19 breakthrough infection was 40.47% (CI 29.82-49.67;p<0.0001), COVID-19 hospitalisation- 69.23% (CI: 50.78-81.64;p<0.00001), ITU admission- 87.89% (CI: 47.12-98.66;p=0.0008), all-cause mortality- 81.29% (66.93-90.28;p<0.0001 and COVID-19-specifc mortality- 86.36% (CI:-6.21-99.70;p=0.0351). Conclusion There is a growing body of real-world evidence validating the original PROVENT phase III study regarding the clinical effectiveness of Tixagevimab/Cilgavimab as prophylaxis for immunocompromised groups, notably demonstrating effectiveness during the Omicron wave. This systematic review demonstrates the significant clinical effectiveness of prophylactic Tixagevimb/Cilgavimab at reducing COVID-19 infection, hospitalisation, ITU admission and mortality for immunosuppressed individuals. It is critically important that largerscale and better-controlled studies are performed to highlight the significant clinical benefit of prophylactic antibody treatment in immunocompromised groups.
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Background: Bimekizumab (BKZ) is a monoclonal IgG1 antibody used in the treatment of psoriasis which selectively inhibits interleukin (IL)-17F in addition to IL-17A.1,2 Data pooled over two years have indicated that BKZ is generally well-tolerated.3 We report three-year BKZ pooled safety data in patients with moderate-to-severe plaque psoriasis. Method(s): Safety data were evaluated for all patients who received one or more dose BKZ in four Phase 3 trials (BE SURE [NCT03412747], BE VIVID [NCT03370133], BE READY [NCT03410992], and their ongoing open-label extension BE BRIGHT open-label extension [NCT03598790;data cut-off : 10/23/2021]) and four Phase 2 trials (BE ABLE 1 [NCT02905006], BE ABLE 2 [NCT03010527], PS0016 [NCT03025542], PS0018 [NCT03230292]). Safety data were evaluated separately for patients receiving BKZ dosed 320mg every four weeks (Q4W) or every eight weeks (Q8W). Exposureadjusted incidence rates (EAIRs) for treatmentemergent adverse events (TEAEs) are the incidence of new cases per 100 patient-years (PY). Result(s): Total BKZ exposure was 4,245.3 PY (N=1,789) across Phase 2/3 trials, and 3,876.4 PY (N=1,495) in Phase 3 trials. TEAEs occurred at a rate of 186.1 across Phase 2/3 trials, serious TEAEs at 5.6, and TEAEs leading to discontinuation at 3.5. Eighteen deaths occurred (0.4/100 PY), all unrelated to study treatment except one (relationship unknown). TEAEs occurred less frequently in Q8W- than Q4W-treated patients in Phase 3 trials. Consistent with previous reports, most common TEAEs (EAIR) in Phase 2/3 trials were nasopharyngitis (15.3), oral candidiasis (10.2), and upper respiratory tract infection (7.1).3 EAIR of serious infections was 1.2. Most frequently reported were serious coronavirus infections (0.2). There were no cases of active tuberculosis. EAIR of oral candidiasis was 10.2, decreased vs two-year data (12.6),3 and was less common with BKZ Q8W vs Q4W. The vast majority of oral candidiasis events were mild or moderate (99.4%);none were serious. EAIRs of hepatic events (4.0) and elevated liver enzymes (3.4) were decreased vs. two-year data (4.3 and 3.6, respectively).3 EAIRs for inflammatory bowel disease (0.1), adjudicated major adverse cardiac events (0.6), and adjudicated suicidal ideation and behavior (0.1) were low. EAIRs for other safety topics of interest were also low and were similar to or lower than two-year EAIRs.3 Conclusion(s): BKZ was well-tolerated over three years. No safety signals were identified;EAIRs of TEAEs did not increase compared with data from two years.3.
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Introduction & Objectives: Bladder preservation is routinely used as an alternative to radical cystectomy in the UK and is becoming more accepted elsewhere globally. The gold standard is for patients to receive radiotherapy with a radiosensitiser most commonly concurrent chemotherapy e.g. 5FU/mitomycin C, gemcitabine or cisplatin. Patients with poor performance status or comorbidities may be unable to be offered concurrent treatment with chemotherapy but alternative treatment with concurrent carbogen +/- nicotinamide as a hypoxic modifier may be of benefit. Our aim therefore was to retrospectively review patients with bladder TCC treated with radical radiotherapy alone in the last 5 years who may have benefited from carbogen +/- nicotinamide radiosensitisation at a large cancer centre in the north of England. Material(s) and Method(s): In this single institution retrospective case note review, electronic records were reviewed for 175 patients who had received radiotherapy to the bladder for TCC between 2017-2022. Patients who had radical radiotherapy (RT) alone without radiosensitisation were scrutinised to ascertain whether they would have been candidates for carbogen and nicotinamide using the inclusion/exclusion criteria previously defined in the Bladder Carbogen Nicotinamide (BCON) Randomised Phase 3 trial. Result(s): We analysed 175 patients. Of these, 133 received had radical RT without radiosensitisation. The most common reason for not offering radiosensitisation was the presence of co-morbidities (27.8%). Of interest, the proportion of patients having chemotherapy radiosensitisation did not change after COVID19 in March 2020 (21.5% pre- vs 27.5% post;p=0.32 chi2). Conversely, the proportion of patients receiving neo-adjuvant chemotherapy reduced though failed to reach significance (12.6% pre- vs 5% post;p=0.08 chi2). After review of the notes and criteria from the original BCON trial, 106 patients (79.6%) could have benefited from carbogen +/- nicotinamide. Of these, 14 patients (13.2%) could have been offered carbogen alone due to poor renal function. The most common reason for not being eligible for BCON was respiratory disease with reduced respiratory drive (44%). Conclusion(s): The National Institute for Health and Care Excellence (NICE) state that all radical RT for bladder TCC should be with a radiosensitiser. Due to logistical and departmental issues, the BCON regimen is not currently offered as a standard alternative to radiosensitisation with chemotherapy. BCON has been demonstrated to be tolerable and, whilst updated follow-up data failed to demonstrate statistical significance for overall survival (OS), meta-analysis of hypoxia modification has shown significant improvement in OS compared to RT alone. Hypoxia modification with carbogen +/- nicotinamide should be considered for all patients unsuitable for chemotherapy radiosensitisation.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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Background: During the eleven months of the novel SARS-CoV-2 disease (COVID-19) outbreak in China and its global spread, there is a remarkable understanding of its epidemiology, pathobiol-ogy, and clinical management strategies. While countering a heavy toll on health and the economy, world's regional authorities are enforcing safety guidelines and providing patient care. Currently, there is no globally approved treatment or intervention for COVID-19. Method(s): A structured online literature search for peer-reviewed articles was conducted on PubMed, Europe PMC, Google, WHO, CDC, FDA, and ClinicalTrials portals, using phrases such as COVID-19 treatment and intervention, COVID-19 drugs and COVID-19 vaccines. Result(s): Analysis of the retrieved data showed that as a part of 'Solidarity Clinical Trials', hundreds of treatment and intervention strategies, including antiviral drugs, cytokine antagonists, convalescent plasma therapy, and vaccine candidates, have been registered worldwide. While remdesivir, the anti-Ebola virus drug, has been approved as an 'emergency use' drug in the USA, favipiravir, the anti-flu drug, has been recently approved in Russia. Tocilizumab and sarilumab, the cytokine (IL-6) antagonists, have entered Phase-II/III clinical trials in hospitalized COVID-19 patients. Among the leading vaccine candidates, Phase-III clinical trial results of Moderna, Pfizer and Oxford vaccines seem to be game changers for COVID19. Conclusion(s): The world health authorities have strongly and quickly responded to the COVID-19 pan-demic. Nonetheless, world bodies must unite in combating this health crisis by developing cost-effective drugs and vaccines and making them accessible to resource-poor countries.Copyright © 2021 Bentham Science Publishers.
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The Coronavirus Disease 2019 (COVID-19), also known as a novel coronavirus (2019-n-CoV), reportedly originated from Wuhan City, Hubei Province, China. Coronavirus Disease 2019 rapidly spread all over the world within a short period. On January 30, 2020, the World Health Organization (WHO) declared it a global epidemic. COVID-19 is a Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) evolves to respiratory, hepatic, gastrointestinal, and neurological complications, and eventually death. SARS-CoV and the Middle East Respiratory Syndrome coron-avirus (MERS-CoV) genome sequences similar identity with 2019-nCoV or Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). However, few amino acid sequences of 2019-nCoV differ from SARS-CoV and MERS-CoV. COVID-19 shares about 90% amino acid sequence simi-larity with SARS-CoV. Effective prevention methods should be taken in order to control this pandemic situation. To date, there are no effective treatments available to treat COVID-19. This review provides information regarding COVID-19 history, epidemiology, pathogenesis and molecular diagnosis. Also, we focus on the development of vaccines in the management of this COVID-19 pandemic and limiting the spread of the virus.Copyright © 2022 Bentham Science Publishers.
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Coronavirus disease 2019 (COVID-19) outbreak started in Wuhan, China when people started with the symptoms of respiratory disorder. The onset of this disease have symptoms like fever, dry cough, fatigue, and difficulty in breathing. The nature of SARS-CoV-2 seems highly contagious as it also can be spread with asymptomatically infected individuals. It has been more than a year which this outbreak have been announced as a pandemic by World Health Organization (WHO) due to major public health crisis and uncontrollable around the globe. Some countries have taken initiatives in inventing vaccines and step up in the clinical trial process since a vaccine is an all-powerful tool which it always been a saviour in fighting infectious disease. In searching for the vaccine, researchers had studied the previously published article of SARS-CoV or MERS as in the beginning, in light, there will be a suitable vaccine to fight this pandemic situation. Recent research on the vaccine has been tested to seek the right vaccine for COVID-19. This study is to focus on the current vaccine development against COVID-19 and to explore the potential vaccines' characteristics that have been studied by the previous proven research findings. This review was done based on the research articles and reviews published until the end of April 2021 through established scientific search engines and related scientific platforms based on the inclusion criteria with its related keywords like coronavirus, SARS-CoV-2, COVID-19 Vaccine, clinical trials, and COVID-19 vaccine development. This review summarized a few vaccine candidates that have entered clinical trials and some supported evidence from Phase I until Phase III clinical trial studies that have been published and reported. In this review, 12 vaccine candidates have the potential to against SARS-CoV-2. Thus, their vaccine platform, characteristic as well as its efficacy studies have been discussed.Copyright © RJPT All right reserved.
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OBJECTIVE To summarize the basic information, mechanism of action, pharmacokinetics, efficacy, safety, interactions, and precautions of azvudine, to provide references for its clinical use. METHODS Literatures related to azvudine from the official website of Chinese clinical trial regi stry, clinicaltrials.gov, Pubmed, CNKI and Wanfang were systematically searched and summarized. RESULTS Azvudine is an oral small-molecule corona virus disease(COVID-19) treatment drug independently developed by China. As a nucleoside analogue targeting to viral RNA-dependent RNA polymerases (RdRp), it can inhibit RNA virus reverse transcription process and replication process. The results of phase III clinical trials showed that azvudine could significantly shorten the time of nucleic acid conversion in patients with mild to moderate corona virus disease (COVID-19). Compared with the control group, the azvudine group can significantly shorten the improvement time of pneumonia. For moderate and severe patients, azvudine treatment also showed significant therapeutic effects in the time of nucleic acid conversion, discharge, and rehabilitation. CONCLUSION The drug possesses good safety and tolerability in patients, which provide a choice for the clinical treatment of COVID-19.Copyright © 2022 Chinese Pharmaceutical Association. All rights reserved.
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BACKGROUND: The COVID-19 pandemic demanded pharmaceutical companies to urgently develop new drugs and vaccines. However, it has been said that there may be some regional differences in the volume of drug development during the pandemic. Therefore, the present study compared the number of phase 3 RCTs for COVID-19 conducted in the US, Europe, Japan, or the rest of the world since the pandemic began. METHOD(S): We searched ClinicalTrials.gov, EudraCT, and jRCT (Japan Registry of Clinical Trials) for "double-blind or more, randomized, in progress or completed" We collected a list of phase 3 trials of COVID-19 that met the criteria of "double-blind or greater, randomized, ongoing, or completed." This list was divided into prophylactic and therapeutic according to primary objective. Using this list, the number of clinical trials conducted in Japan, the US, and the EU/UK were aggregated, by sponsor and by site, respectively. RESULT(S): There were 430 trials that met the predefined criteria, of which 140 were prophylactic and 290 were therapeutic. By site, 133 trials were conducted in the US, 127 in the EU and UK, 41 in Japan, and 248 in other regions. By sponsor headquarters, 115 trials were conducted in the US, 115 in the EU and UK, 19 in Japan, and 181 in the rest of the world. CONCLUSION(S): The regional difference in the number of clinical trials for COVID-19 was found. Fewer phase 3 trials of COVID-19 were conducted in Japan than in the US and Europe, suggesting that the drug development in Japan may be slower or less active among the three major regions during the worldwide pandemic.
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OBJECTIVE To summarize the basic information, mechanism of action, pharmacokinetics, efficacy, safety, interactions, and precautions of azvudine, to provide references for its clinical use. METHODS Literatures related to azvudine from the official website of Chinese clinical trial regi stry, clinicaltrials.gov, Pubmed, CNKI and Wanfang were systematically searched and summarized. RESULTS Azvudine is an oral small-molecule corona virus disease(COVID-19) treatment drug independently developed by China. As a nucleoside analogue targeting to viral RNA-dependent RNA polymerases (RdRp), it can inhibit RNA virus reverse transcription process and replication process. The results of phase III clinical trials showed that azvudine could significantly shorten the time of nucleic acid conversion in patients with mild to moderate corona virus disease (COVID-19). Compared with the control group, the azvudine group can significantly shorten the improvement time of pneumonia. For moderate and severe patients, azvudine treatment also showed significant therapeutic effects in the time of nucleic acid conversion, discharge, and rehabilitation. CONCLUSION The drug possesses good safety and tolerability in patients, which provide a choice for the clinical treatment of COVID-19.
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The 32nd European Respiratory Society (ERS) International Congress was held again in person at the FIRA Barcelona Gran Via Conference Center in Spain, as well as online. On-site attendance was limited to 10,000 delegates, with the spaces selling out before the conference began. The program included live streamed presentations, thematic poster discussion sessions, oral presentations, mini-symposia, industry exhibitors and skills workshops to discuss major respiratory fields that included thoracic oncology, respiratory infections, interstitial lung diseases, respiratory critical care, sleep and breathing disorders and pulmonary vascular diseases. This report will cover some of the most interesting presentations related to respiratory disease treatment. Copyright © 2022 Clarivate.
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SESSION TITLE: Using Imaging for Diagnosis Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: The vaccines against SARS-CoV-2 or COVID-19 have been shown to be safe and effective at preventing severe disease and death. In a phase 3 trial the BNT162b2 mRNA COVID-19 vaccine showed a 52% and 95% efficacy after the first and second doses, respectively (1). Side effects following vaccination are common but are typically mild and self limited (2). The most common side effects are headache, fever, fatigue, arthralgias and pain at the injection site (2). More severe and devastating side effects have been reported including cerebral venous thrombosis and myocarditis (3) (4). Here we report a case of unilateral diaphragmatic paralysis following the second dose of the BNT162b2 mRNA COVID-19 vaccine. CASE PRESENTATION: The patient was a 56 year old female with a past medical history of reactive airways disease and hypertension who was seen in the pulmonology clinic shortly after receiving her second dose of the BNT162b2 mRNA COVID-19 vaccine. After her second dose she developed burning shoulder pain, erythema and swelling that extended to the neck and axilla. She went to an urgent care and was advised to treat with ice and NSAIDs, she had a chest radiograph performed which was reported to be negative. Her symptoms persisted and she was sent to the emergency room, chest x-ray showed interval development of an elevated left hemidiaphragm. A CT Chest with inspiratory and expiratory films was performed and the left diaphragm was noted to be in the same location during inspiration and expiration consistent with diaphragmatic paralysis. PFT showed a reduction in her FVC, TLC and DLCO compared to 13 years prior. DISCUSSION: Diaphragmatic paralysis is a well described clinical entity that is most often associated with cardiothoracic surgery where hypothermia and local ice slush application are thought to induce phrenic nerve injury (5). It has also been described as a complication of viral infections, including a recent report of unilateral diaphragm paralysis in a patient with acute COVID-19 infection (6). In a case series of 246 patients with amyotrophic neuralgia which can include diaphragm paralysis, 5 patients received a vaccine in the week before developing symptoms (8) Additionally, Crespo Burrilio et al recently described a case of amyotrophic neuralgia and unilateral diaphragm paralysis following administration of the Vaxzevri (AstraZeneca) COVID-19 vaccine (7). This case highlights a potential side effect of the BNT162b2 mRNA COVID-19 vaccine that has not been previously reported CONCLUSIONS: Reference #1: Polack FP, Thomas SJ, Kitchin N. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med. 2020;383:2603–2615. Reference #2: Menni, C., Klaser, K., May, A., Polidori, L., Capdevila, J., Louca, P., Sudre, C. H., Nguyen, L. H., Drew, D. A., Merino, J., Hu, C., Selvachandran, S., Antonelli, M., Murray, B., Canas, L. S., Molteni, E., Graham, M. S., Modat, M., Joshi, A. D., Mangino, M., … Spector, T. D. (2021). Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study. The Lancet. Infectious diseases, 21(7), 939–949. https://doi.org/10.1016/S1473-3099(21)00224-3 Reference #3: Jaiswal V, Nepal G, Dijamco P, et al. Cerebral Venous Sinus Thrombosis Following COVID-19 Vaccination: A Systematic Review. J Prim Care Community Health. 2022;13:21501319221074450. doi:10.1177/21501319221074450 DISCLOSURES: No relevant relationships by Jack Mann No relevant relationships by John Prudenti
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COVID-19 disease is caused by a novel type of SARS-CoV-2 virus which was firstly described in Chinese Wuhan in December 2019. It is highly infectious disease manifested with fever, respiratory problems, muscle pains and tiredness. Up to now, no efficient medicine has been available, that is why research is focused on development of a vaccine. The vaccine research was launched immediately when the pandemic broke out. The main goal of vaccination against COVID-19 will be prevention of infection outbreak, prevention of reinfection, long-term protective effect and efficiency of vaccination in case of next potential waves of infection. The primary questions are if the effective vaccine against COVID-19 will be developed, how long it will take and who will be the first. The first pandemic disease caused by a novel SARS coronavirus emerged almost 20 years ago, the next MERS coronavirus disease 8 years ago and no effective vaccine against these diseases has been available so far. Presently, 179 candidate vaccines at minimum are at different stages of their development and 18 vaccines are at the stage of clinical evaluation. The surface S glycoprotein SARS-CoV-2 virus is considered the most promising vaccine antigen. Other options are the use of the whole virion or subunit S1 carrier. Currently, four types of potential vaccines have been developed. Whole virion vaccines (attenuated or killed vaccine) vector vaccines (most often using replicating or non-replicating viral vector) protein vaccines (subunit adjuvant vaccine or vaccine based on virus-like particles) and DNA, RNA vaccine. The key moment will be confirmation of the novel vaccine efficiency at the phase 3 of a clinical trial. Despite pressure and efforts to speed up the development of the vaccine, it is realistic to count on the possible vaccine in the year 2021 the earliest and the question is when it can be available in the Czech Republic. Copyright © 2020, Medakta s.r.o.. All rights reserved.
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Background: AAP or ENZ added to ADT improves outcomes for mHSPC. Any benefit of combining ENZ & AAP in this disease setting is uncertain. Methods: STAMPEDE is a multi-arm, multi-stage (MAMS), platform protocol conducted at 117 sites in the UK & Switzerland. 2 trials with no overlapping controls randomised mHSPC patients (pts) 1:1 to ADT +/- AAP (1000mg od AA + 5mg od P) or AAP + ENZ (160mg od). Treatment was continued to progression. From Jan 2016 docetaxel 75mg/m2 3-weekly with P 10mg od was permitted + ADT. Using meta-analysis methods, we tested for evidence of a difference in OS and secondary outcomes (as described previously: failure-free, metastatic progression-free, progression-free & prostate cancer specific survival) across the 2 trials using data frozen 3 Jul 2022. All confidence intervals (CI) 95%. Restricted mean survival times (RMST) restricted to 84 months (m). Results: Between Nov 2011 & Jan 2014, 1003 pts were randomised ADT +/- AAP & between Jul 2014 & Mar 2016, 916 pts were randomised ADT +/- AAP + ENZ. Randomised groups were well balanced across both trials. Pt cohort: age, median 68 years (yr), IQR 63, 72;PSA prior to ADT, median 95.7 ng/ml, IQR 26.5, 346;de novo 94%, relapsed after radical treatment, 6%. In AAP + ENZ trial, 9% had docetaxel + ADT. OS benefit in AAP + ENZ trial, HR 0.65 (CI 0.55‒0.77) p = 1.4×10-6;in AAP trial, HR 0.62 (0.53, 0.73) p = 1.6×10-9. No evidence of a difference in treatment effect (interaction HR 1.05 CI 0.83‒1.32, p = 0.71) or between-trial heterogeneity (I2 p = 0.70). Same for secondary end-points. % (CI) of pts reporting grade 3-5 toxicity in 1st 5 yr: AAP trial, ADT: 38.5 (34.2-42.8), + AAP: 54.4 (50.0-58.8);AAP + ENZ trial, ADT: 45.2 (40.6 – 49.8), + AAP + ENZ: 67.9 (63.5 – 72.2);most frequently increased with AAP or AAP + ENZ = liver derangement, hypertension. At 7 yr in AAP trial (median follow-up: 95.8m), % (CI) pts alive with ADT: 30 (26, 34) versus with ADT + AAP: 48 (43, 52);RMST: ADT: 50.4m, ADT + AAP: 60.6m, p = 6.6 x 10-9. Conclusions: ENZ + AAP need not be combined for mHSPC. Clinically important improvements in OS when adding AAP to ADT are maintained at 7 yr. Clinical trial identification: NCT00268476. Legal entity responsible for the study: Medical Research Council Clinical Trials Unit at University College London. Funding: Cancer Research UK, Medical Research Council, Janssen, Astellas. Disclosure: G. Attard: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca;Financial Interests, Personal, Advisory Board: Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion;Financial Interests, Personal, Royalties, Included in list of rewards to discoverers of abiraterone: Institute of Cancer Research;Financial Interests, Institutional, Research Grant: Janssen, Astellas;Non-Financial Interests, Principal Investigator: Janssen, Astellas;Non-Financial Interests, Advisory Role: Janssen, AstraZeneca. W.R. Cross: Financial Interests, Personal, Invited Speaker, Speaker fee: Myriad Genetics, Janssen, Astellas;Financial Interests, Personal, Advisory Board, Advisory Board fee: Bayer;Financial Interests, Institutional, Research Grant, Research grant: Myriad Genetics. S. Gillessen: Financial Interests, Personal, Advisory Board, 2018: Sanofi, Roche;Financial Interests, Personal, Advisory Board, 2018, 2019: Orion;Financial Interests, Personal, Invited Speaker, 2019 Speaker's Bureau: Janssen Cilag;Financial Interests, Personal, Advisory Board, 2020: Amgen;Financial Interests, Personal, Invited Speaker, 2020: ESMO;Financial Interests, Personal, Other, Travel Grant 2020: ProteoMEdiX;Financial Interests, Institutional, Advisory Board, 2018, 2019, 2022: Bayer;Financial Interests, Institutional, Advisory Board, 2020: Janssen Cilag, Roche, MSD Merck Sharp & Dohme, Pfizer;Financial Interests, Institutional, Advisory Board, 2018: AAA International, Menarini Silicon Biosystems;Financial Interests, Institutional, Advisory Board, 2019, 2020: Astellas Pharma;Financial Interests, Institutional, Advisory B ard, 2019: Tolero Pharmaceuticals;Financial Interests, Personal, Invited Speaker, 2021, 2022: SAKK, DESO;Financial Interests, Institutional, Advisory Board, 2021: Telixpharma, BMS, AAA International, Novartis, Modra Pharmaceuticas Holding B.V.;Financial Interests, Institutional, Other, Steering Committee 2021: Amgen;Financial Interests, Institutional, Advisory Board, 2021, 2022: Orion, Bayer;Financial Interests, Personal, Invited Speaker, 2021: SAKK, SAKK, SAMO - IBCSG (Swiss Academy of Multidisciplinary oncology);Financial Interests, Personal, Advisory Board, 2021: MSD Merck Sharp & Dhome;Financial Interests, Personal, 2021: RSI (Televisione Svizzera Italiana);Financial Interests, Institutional, Invited Speaker, 2021: Silvio Grasso Consulting;Financial Interests, Institutional, Other, Faculty activity 2022: WebMD-Medscape;Financial Interests, Institutional, Advisory Board, 2022: Myriad genetics, AstraZeneca;Financial Interests, Institutional, Invited Speaker, 2022: TOLREMO;Financial Interests, Personal, Other, Travel support 2022: AstraZeneca;Financial Interests, Institutional, Funding, 2021, Unrestricted grant for a Covid related study as co-investigator: Astellas;Non-Financial Interests, Advisory Role, 2019: Menarini Silicon Biosystems, Aranda;Non-Financial Interests, Advisory Role, Continuing: ProteoMediX. C. Pezaro: Financial Interests, Personal, Advisory Board, Ad board Dec 2020: Advanced Accelerator Applications;Financial Interests, Personal, Advisory Board, Aug 2021: Astellas;Financial Interests, Personal, Advisory Board, Oct 2021: Bayer;Financial Interests, Personal, Invited Speaker, Sept-Oct 2020: AstraZeneca;Financial Interests, Personal, Invited Speaker, Oct 2020: Janssen;Financial Interests, Personal, Advisory Board, July-Sept 2022: Pfizer. Z. Malik: Financial Interests, Personal, Advisory Board, advisry board for new hormonal therapy for breast cancer: sanofi;Financial Interests, Institutional, Invited Speaker, research grant for CHROME study: sanofi;Other, Other, support to attend meetings or advisory boards in the past: Astellas,Jaansen,Bayer;Other, Other, Sponsorship to attend ASCO meeting 2022: Bayer. M.R. Sydes: Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training sessions for clinicians (no discussion of particular drugs): Janssen;Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training session for clinicians (no discussion of particular drugs): Eli Lilly;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Astellas, Janssen, Novartis, Pfizer, Sanofi;Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology. L.C. brown: Financial Interests, Institutional, Research Grant, £170k educational grant for the FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca;Financial Interests, Institutional, Funding, Various grants awarded to my institution for work undertaken as part of the STAMPEDE Trial: janssen pharmaceuticals;Non-Financial Interests, Other, I am a member of the CRUK CERP funding advisory panel and my Institution also receive grant funding from CRUK for the STAMPEDE and FOCUS4 trials: Cancer Research UK. M.K. Parmar: Financial Interests, Institutional, Full or part-time Employment, Director at MRC Clinical Trials Unit at UCL: Medical Research Council Clinical Trials Unit at UCL;Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis;Non-Financial Interests, Advisory Role, Euro Ewing Consortium: University College London;Non-Financial Interests, Advisory Role, rEECur: University of Birmingham;Non-Financial Interests, Advisory Role, CompARE Trial: University of Birmingham. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen, Clovis, Novartis;Financial Interests, Institutional, Expert Testimony, Assisted with submissions regarding licencing for abiraterone: Janssen;Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi;Financial Interests, Institutional, Expert Testimony, Providing STAMPEDE trial data to facilitate licence extensions internationally for docetaxel: Sanofi;Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck;Financial Interests, Personal, Advisory Board, Advice around novel hormone therapies for prostate cancer: Bayer;Financial Interests, Personal, Invited Speaker, Lecture tour in Brazil August 2022 - speaking on therapy for advanced prostate cancer: Merck Sharp & Dohme (UK) Limited;Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Janssen, Astellas;Financial Interests, Institutional, Invited Speaker, Funding for RADIO trial bladder cancer: AstraZeneca. All other authors have declared no conflicts of interest.