Category: 3. Business

  • Amazon Web Services outage: 6.5m reports of disruption as many websites and apps hit – business live | Business

    Amazon Web Services outage: 6.5m reports of disruption as many websites and apps hit – business live | Business

    Full story: Amazon Web Services outage hits dozens of websites and apps

    Dan Milmo

    A major internet outage has hit dozens of websites and apps around the world, with users reporting troubles getting online after problems at Amazon’s cloud computing service.

    The affected platforms include Snapchat, Roblox, Signal and Duolingo as well as a host of Amazon-owned operations including its main retail site and the Ring doorbell company.

    In the UK, Lloyds bank was affected as well as its subsidiaries Halifax and Bank of Scotland, while there were also reports of problems accessing the HM Revenue and Customs website on Monday morning. Also in the UK, multiple Ring users took to social media to complaint their doorbells were not working.

    In the UK alone reports of problems on individual apps ran into the tens of thousands for each platform. More here:

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    Key events

    Amazon’s cloud services unit AWS is struggling to recover from a widespread outage that knocked out thousands of websites along with some of the world’s most popular apps – Snapchat and Reddit – and disrupted businesses globally, Reuters reports.

    After more than six hours of disruptions, some applications were gradually coming back online as of 10:00 a.m. ET (3pm UK time). But AWS acknowledged it was still experiencing elevated errors.

    In its latest status update, AWS says:

    “We can confirm significant API errors and connectivity issues across multiple services … We are investigating,”

    To aid the recovery, AWS said it was putting in place limits on the number of requests that can be made on its platform.

    While some apps like Reddit and Roblox had largely stabilised, according to outage tracking website Downdetector, others, including Snapchat and Duolingo, were showing a resurgence in issues seen earlier in the day.

    Indeed, this chart shows how reports of outages at Snapchat rose an hour ago:

    Photograph: Downdetector
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  • PCAOB Concludes 2025 Conference on Auditing and Capital Markets

    On October 17, the Public Company Accounting Oversight Board (PCAOB) concluded its 12th annual Conference on Auditing and Capital Markets, an event designed to foster rigorous economic research on audit-related topics, including the economic impact of auditing, audit regulation, and audit oversight on capital markets.

    The two-day conference, held this year in conjunction with The Accounting Review, drew more than 115 researchers from around the world to Washington.

    “A sound and sustainable approach to audit regulation depends on having access to data-driven assessments of how standards and rules ultimately impact auditing and, by extension, the users of financial statements,” said PCAOB Acting Chair George R. Botic. “The academic community has long played an invaluable role in that regard, and the insightful studies presented this year strengthen the foundation for evidence-based auditing standards and rules.”

    Ten research papers were chosen for presentation at the conference out of 88 submitted in response to the PCAOB’s call for papers. The papers presented addressed:

    • Auditing and management disclosures
    • Private equity investment in accounting firms
    • The labor market for auditors
    • Auditor independence
    • The impact of regulation on non-capital market audits

    The papers were selected for presentation following a blind review by a program committee of PCAOB staff and academic experts. The Accounting Review will invite those authors whose projects appear particularly promising to submit that research for review and consideration for publication.

    “The research presented at this conference is essential to advancing evidence-based oversight and policy,” said Dr. Joshua T. White, the PCAOB’s Acting Chief Economist and Director of its Office of Economic and Risk Analysis. “By delivering high-quality, data-driven insights, these studies not only expand our knowledge of how audits and audit regulation affect the capital markets, but also directly enhance the PCAOB’s ability to protect investors.

    The conference agenda is available on the PCAOB website. Links to the working papers presented at the conference will remain available through November 21, 2025. After this date, interested parties should contact the authors to obtain the most current versions of their papers.

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    About the PCAOB

    The PCAOB is a nonprofit corporation established by Congress to oversee the audits of public companies in order to protect investors and further the public interest in the preparation of informative, accurate, and independent audit reports. The PCAOB also oversees the audits of brokers and dealers registered with the Securities and Exchange Commission, including compliance reports filed pursuant to federal securities laws.

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  • Baker McKenzie advises Fellowmind on its acquisition of Xperity | Newsroom

    Baker McKenzie advises Fellowmind on its acquisition of Xperity | Newsroom

    Baker McKenzie has advised international IT service provider Fellowmind on its acquisition of Xperity, expert in Microsoft Dynamics 365 CRM. The joining of forces is part of Fellowmind’s international growth strategy and strengthens its position as a Microsoft partner worldwide.

    Fellowmind is a leading Microsoft partner and part of the top 1% of Microsoft partners worldwide. With Xperity on board, Fellowmind expands its CRM expertise and increases its market share within the manufacturing industry, business services, and healthcare. This allows Fellowmind to even better support existing and new customers in strengthening customer relationships, centralizing customer data, and using AI to optimize sales, service, and marketing departments.

    Baker McKenzie provided legal advisory services to Fellowmind, with the core team including Joost Polman as team lead, along with Philip Lückmann and Daan Paquay.

    Further information is available on the company website:
    • Xperity joins Fellowmind

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  • Exclusive: Instagram shows more ‘eating disorder adjacent’ content to vulnerable teens, internal Meta research shows – Reuters

    1. Exclusive: Instagram shows more ‘eating disorder adjacent’ content to vulnerable teens, internal Meta research shows  Reuters
    2. Instagram Shows More Eating Disorder-Adjacent Content to Vulnerable Teens, Internal Research Finds  The Boca Raton Tribune
    3. Instagram shows more ‘eating disorder-related’ content to vulnerable teens  Latest news from Azerbaijan

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  • As ANZ duped customers and ignored hardship notices, the bank’s bosses raked in $26m in bonuses | ANZ

    As ANZ duped customers and ignored hardship notices, the bank’s bosses raked in $26m in bonuses | ANZ

    The bank charged fees on dead people’s accounts, ignored hardship notices and misled customers. But over those same three years, ANZ bosses were awarded more than $26m in bonuses.

    Now, shareholder proxy firms are waiting until December to see whether bonuses will be cut in response to the record $240m in fines given for ANZ’s widespread misconduct.

    The short-term bonuses, awarded to 11 executives between 2021-22 and 2023-24, have been condemned as indefensible and “completely out of touch” by the Finance Sector Union, which has been assisting some of the 3,500 ANZ staff whose jobs will be cut by next September.

    People walk past an ANZ Bank building, Photograph: Jaimi Joy/Reuters

    The bonuses have also been criticised by the Greens as an example of “how broken the system is”, with the total amount paid out over the three-year period exceeding some of the fines ANZ received from the Australian Securities and Investments Commission (Asic).

    Ahead of a shareholder revolt at last year’s annual general meeting, ANZ’s former chief executive Shayne Elliott gave up a long-term bonus worth $3.2m. But Elliott’s short-term bonuses of $5.5m over the three years were not affected.

    Other top executives were paid $3.2m, $3.1m and $2.8m in bonuses during the three-year period.

    “That’s indefensible and completely out of touch with what the community expects,” said the FSU’s national president, Wendy Streets.

    “At a time when ANZ is slashing 3,500 roles to save $800m offshoring jobs and apologising for compliance failures, these payouts are tone-deaf and unjustifiable.”

    Corporate bonuses in focus

    The ANZ case is just one example of bonuses being awarded to top staff, despite community outrage and regulatory action over a company’s conduct.

    Guardian Australia on Monday revealed health insurer Bupa had declared $14.1m in bonuses for senior staff a year before it agreed to pay a $35m fine for “unconscionable conduct”. The chief executive of the childcare giant G8 Education also secured a short-term bonus of $534,426 last year, despite multiple safety breaches and the employment of a man subsequently charged with child sexual offences

    In ANZ’s case, the bank last month accepted its failure to respond to 488 customers who submitted hardship notices between May 2022 and September 2024, which resulted in the $240m in penalties. In some cases, ANZ took more than two years to respond to requests for help.

    It was separately ordered to pay a $25m fine for failing to provide promised benefits to customers in 2022. ANZ also faced a $10m fine for contravening the credit act during the same financial year, while separately helping the sovereign debt management agency with a $14bn bond issuance in a way that exposed the government to a “significant risk of harm”, according to the financial regulator.

    Australia and New Zealand Banking Group Limited (ANZ Bank) CEO Shayne Elliott. Photograph: Mick Tsikas/AAP

    In that same financial year, eight senior ANZ executives received short-term annual bonuses worth $8.24m – an average of $1m each.

    The following financial year, ANZ was ordered to pay a $15m fine for misleading customers about credit available in their accounts. It also faced a $900,000 fine for breaching continuous disclosure obligations. In August 2023, it told the government it overstated bonds trading data, describing this as an “unacceptable failure”.

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    But during that 12-month period, 11 senior executives were paid short-term bonuses totalling $10.5m.

    These payments were roughly 58% of the maximum bonus available, which was less than the 66% average across the ASX200, according to an analysis by the Australian Council of Superannuation Investors (Acsi).

    On 2 July 2024, ANZ was sanctioned for not stopping or refunding fees charged to dead people between July 2019 and September 2023. Almost 19,000 customers were affected. The Banking Code Compliance Committee described the breaches as serious and systemic.

    ANZ declined to comment when contacted last week over its payment of bonuses.

    The bank has apologised on numerous occasions for the breaches and pledged to overhaul its culture.

    In September, the bank’s chair, Paul O’Sullivan, said more than 50 “accountability reviews” had been conducted in its markets division as a result of Asic’s action.

    “It has resulted in significant impacts to variable remuneration for certain individuals,” O’Sullivan said last month. Those impacts will not be known until later this year shortly before the bank’s annual general meeting in December.

    Greens senator Nick McKim says the executive culture at Australia’s banks ‘hasn’t changed’ since the royal commission. Photograph: Mick Tsikas/AAP

    The Greens senator Nick McKim said the lucrative bonuses showed “how broken the system is”.

    “The culture at the top of Australia’s banks hasn’t changed since the royal commission,” McKim said, adding the people who presided over the bank at the time of the wrongdoing “are still cashing in”.

    According to Acsi’s research, only one of 142 chief executives at ASX200 companies who were eligible for a bonus didn’t receive one last financial year.

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  • Kering chief vows rapid overhaul after sealing €4bn beauty deal

    Kering chief vows rapid overhaul after sealing €4bn beauty deal

    Kering’s new chief executive has vowed to make sweeping changes in an urgent bid to refocus the luxury group on fashion, as it announced a €4bn deal to sell its beauty operations to L’Oréal.

    Luca de Meo signalled that he planned to make several big changes to the Gucci-owner, one of the world’s top luxury groups, saying he had moved to seal the beauty deal “as quickly as possible” and promising that “you’ll see others”.

    The luxury sector enjoyed a boom during the pandemic, driven by housebound consumers spending more on high-end goods and huge growth in the Chinese market, but has since been hit by consumers reining in spending and a faltering Chinese economy.

    De Meo, brought in from Renault where he led a large turnaround of another of France’s top listed companies, said his top priority was to refocus Kering on its fashion brands, notably Gucci. As well as beauty and fashion, the group also sells eyewear, while its jewellery houses include Boucheron.

    “The urgency is to focus on the things . . . where we have a critical size and skills. That will help me lighten the boat and be able to focus on the relaunch of fashion brands,” de Meo told the Financial Times in an interview on Monday after Kering announced the sale of its beauty business.

    He added that he wanted to “inject more speed into some of our decisions”.

    The group’s flagship label — which accounts for about half of its sales and two-thirds of profits — has fallen out of favour with consumers in a challenging luxury market. It also suffered from over-dependence on China when demand in the country slowed.

    Luca de Meo, left, with L’Oréal chief Nicolas Hieronimus. ‘I’ve always believed that speed is important in modern business,’ said Kering’s new chief © Nathaniel Goldberg

    Under the terms of the deal, L’Oréal is buying perfumer House of Creed, as well as 50-year licences to develop and sell fragrances under the Gucci, Bottega Veneta and Balenciaga labels. The French beauty giant will pay undisclosed royalties to Kering in return.

    The talks, which had begun before de Meo arrived from Renault, sped up from August, according to people with knowledge of the situation.

    Kering’s chief said he remained “pragmatic” with regard to other potential asset sales, including a possible disposal of its successful eyewear division.

    “I don’t want to close the door because we try to be very open,” de Meo said, before highlighting that Kering’s eyewear business was important to some of its most valuable clients and that it was the industry leader on the highest-end segments.

    Kering’s shares were up 4.1 per cent on Monday afternoon, extending a rally of more than 80 per cent over the past six months, on the back of hopes that de Meo can turn the group around and that the broader malaise in the luxury industry is easing.

    “I’ve always believed that speed is important in modern business,” said de Meo.

    “As soon as I saw that I had this opportunity, I tried with Nicolas [Hieronimus, chief executive of L’Oréal] to work so that we could conclude [the deal] as quickly as possible. And you’ll see others,” he added.

    a Creed Aventus eau de parfum bottle placed among fanned playing cards inside a vintage cabinet.
    L’Oréal is buying perfumer House of Creed from Kering © Tomas Darguzis/Alamy

    UBS analyst Zuzanna Pusz said the deal would help Kering reduce its debt, thus tackling “one of the biggest investor concerns”.

    Pusz calculates that the proceeds could reduce Kering’s net debt from 3.1 times earnings before interest, tax, depreciation and amortisation to roughly 2 times, which may outweigh impairments that the group has taken on parts of its beauty business. Kering acquired Creed for €3.5bn only two years ago.

    For L’Oréal, the deal marks its biggest-ever acquisition. Hieronimus said it would cement its status as the market leader in high-end beauty, and that L’Oréal would focus its efforts initially on developing Creed.

    L’Oréal’s chief said in an interview that he hoped to almost triple Creed’s annual revenues to €1bn “fairly quickly”. The group’s shares edged up by 0.3 per cent on Monday.

    L’Oréal will not get its hands on the licence for Gucci, which is expected to ultimately prove the most valuable, until a deal with beauty group Coty expires in 2028.

    “Obviously, having the opportunity, when it is legally possible, to recover the Gucci brand was one of our motivations,” said Hieronimus. 

    L’Oréal has form for growing high-end beauty brands. Revenues at Aesop, the upmarket soap maker it bought two years ago for $2.5bn, increased by about 10 per cent in 2024, according to one person close to the business.

    Shelves neatly stocked with various Aesop skincare products in bottles, jars, and boxes, arranged by type and size.
    L’Oréal bought Aesop two years ago for $2.5bn © Tea/Dreamstime

    The French group, which holds the beauty licence for Yves Saint Laurent, another Kering brand, generates about €3bn in annual beauty revenues from it, according to Hieronimus. That is slightly above YSL’s €2.9bn of fashion sales last year.

    This implies that there is substantial opportunity to grow Gucci’s beauty range, which Hieronimus said generated only about €600mn in revenues last year, compared with the label’s €7.7bn of fashion revenues.

    “When you look at the positioning of Gucci in this segment, there is room for improvement,” acknowledged de Meo. 

    Spanish fragrance and fashion group Puig also took an interest in Kering’s beauty division, according to two people with knowledge of the situation. Puig declined to comment.

    But in the end, the people said, the deal with L’Oréal offered a more logical and expansive partnership. 

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  • Angola’s €200mn water infrastructure project bags HSBC financing, ECA backing 

    Angola’s €200mn water infrastructure project bags HSBC financing, ECA backing 

    The Angolan government and HSBC have reached financial close on the €200mn water infrastructure ProÁgua project, which is set to modernise water supply systems and provide millions across the country with access to clean drinking water 

    The loan agreements were signed between the Ministry of Finance of Angola, representing the sovereign borrower, and the bank, with export credit agency (ECA) cover provided by Bpifrance Assurance Export and the Swiss Export Risk Insurance (Serv). 

    The project is being executed by a consortium of Swiss company Mitrelli and French multinational Suez International.

    Its financing consists of two tranches: a commercial loan facility for financing the downpayment in the amount of €30mn (equating to 15% of the total project amount), and an ECA-backed buyer’s credit financing the remaining 85% of the project, totalling €170mn. 

    The financing structured reflects a “robust, de-risked model for infrastructure investment in emerging markets”, Mitrelli and Suez said in a dual statement. 

    HSBC acted as sole coordinating arranger, mandated lead arranger and facility agent. The bank played a “central role in originating, structuring, and executing the financing while facilitating efficient disbursement mechanisms and long-term repayment structures”, according to the statement. 

    Meanwhile, Bpifrance Assurance Export issued “comprehensive export credit insurance, enabling favourable terms of the financing and risk mitigation”, together with Serv, which provided reinsurance, according to the stakeholders. 

    Their export credit insurance “enabled Angola to access long-tenor financing at competitive rates, while also supporting French and Swiss exports”, they said. 

    This transaction also represents the first time Bpifrance has issued its export credit insurance based on direct commitments from a Swiss engineering, procurement and construction contractor outside of France. 

    The ProÁgua project will expand and modernise water access across the provinces of Luanda and Icolo e Bengo. According to the Angolan government, it will deliver clean water to over nine million people, addressing urgent needs in a region where only 34% of the rural population currently has access to safe drinking water. 

    The infrastructure project will include the rehabilitation of four major water treatment plants, construction of two decentralised compact units, installation of six desalination units and 15 boreholes, and the deployment of smart metering and digital utility management systems. 

    It will be executed with Angola’s public water utility as the local implementation partner.  

    A second phase of the project is already under discussion among the parties, aiming to extend access to safe drinking water to more people across the country. 

    This latest financing follows other ECA-backed water projects in east Africa in recent years, including a US Exim-supported solar and water project in Angola, a UKEF-sponsored infrastructure upgrade in the same country, and a joint ECA loan for a wide-scale Côte d’Ivoire water availability initiative.

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  • A new generation of Euroclusters to strengthen industrial resilience across Europe

    A new generation of Euroclusters to strengthen industrial resilience across Europe

    16 new Euroclusters were selected for funding under the call Joint Cluster Initiatives (Euroclusters) for Europe’s Recovery (SMP-COSME-2024-CLUSTER). With an overall budget of €42 million, the new partnerships will advance the EU’s ambition for a greener, more digital and more resilient industrial future.

    Starting in October 2025 and running for a period up to 3 years, the 16 new Euroclusters, funded through the Single Market Programme, represent 107 beneficiaries from 26 countries and cover all 14 industrial ecosystems.

    More than 30 million EUR of the Euroclusters budget will be channeled directly to SMEs through open calls organised by the consortia. This support will fund projects that: 

    • foster innovation and the uptake of advanced technologies,
    • build capacity in strategic sectors, and
    • drive Europe’s transformation towards a sustainable, digital and resilient economy. 

    Additional activities, including training, internationalisation and knowledge exchange will complement this main objective, helping small businesses expand their innovation potential and connect with new partners across borders. 

    The 16 Euroclusters are divided into two strands, focusing respectively on net-zero technologies and critical raw materials (Strand 1), and on other strategic value chains (Strand 2). 

    To see the whole list of the new Euroclusters and know more about each of them, read the article on the European Cluster Collaboration Platform (ECCP) website.

    More information 

    European Cluster Collaboration Platform 

    To keep updated on the Euroclusters activities and achievements, follow the ECCP via their Social Media accounts on Twitter  and  LinkedIn and subscribe to the monthly ECCP newsletter.


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  • Intern/Working student (m/f/d) – Simulation of Electric Machines | Careers

    Intern/Working student (m/f/d) – Simulation of Electric Machines | Careers

    We are currently hiring for an exciting opportunity as an Intern or as a Working student (m/f/d) – SIMULIA EMAG to join our team.

    The EMAG Workflow Management team in the SIMULIA organization is closely linked with EMAG RnD team as well with Tech Sales teams. The team is involved in defining, testing and documenting sales relevant and strategically important workflows. The e-machine topic is one of the important drivers, in which DS and Simulia plans to grow into higher market shares. And here the AI capabilities will be a critical part, in which knowledge and knowhow need to be developed.

    Role Description & Responsibilities

    • You will contribute to the topic of electric machine simulation
    • You will analyze losses and thermal aspects of electric machines, also in regard of reduced order models to run realistic thermal network simulation
    • You will contribute to testing newly developed software parts

     

    Qualifications
     

    • You are currently studying Engineering or Mechatronics
    • You have good scripting knowledge in Python
    • You have basic experience with numerical simulation such as finite elements
    • You have a basic understanding of with electric machines or other energy transforming devices
    • You have good English language skills

     

    What’s in it for you

    • Flexible working hours with the possibility to work partially outside the office
    • Learning from and working with highly qualified, dedicated and diverse teams
    • Possibility for professional development in many different domains within our 3DEXPERIENCE University and LinkedIn Learning programs
    • Additional benefits & perks such as Urban Sports Club membership (because who doesn’t love staying fit while having fun?) and of course, unlimited coffee, fruit, and drinks at the office, we’ve got you covered 😉

    Interested? Click on “Apply” to access the 3DS job portal and to upload your application documents.
    Let’s open new horizons together with the power of 3DEXPERIENCE virtual universes! Shape your career with 3DS! #WeAre3DS

     

    Inclusion statement

    As a game-changer in sustainable technology and innovation, Dassault Systèmes is striving to build more inclusive and diverse teams across the globe. We believe that our people are our number one asset and we want all employees to feel empowered to bring their whole selves to work every day. It is our goal that our people feel a sense of pride and a passion for belonging. As a company leading change, it’s our responsibility to foster opportunities for all people to participate in a harmonized Workforce of the Future.

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  • REASSURE Data Affirm Safety of Radium-223 in mCRPC, Underscore Need for Bone Protection

    REASSURE Data Affirm Safety of Radium-223 in mCRPC, Underscore Need for Bone Protection

    In an analysis of 7-year follow-up data from the REASSURE study, Bertrand Tombal, MD, emphasized that the findings remain true to the study’s name—reassuring. The results show no significant increase in hematologic toxicity with Radium-223 in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases, while highlighting the critical importance of timing and bone health management.

    In an interview with Pharmacy Times, Tombal discussed key takeaways for clinicians and pharmacists, including the need to paid Radium-223 with agents such as denosumab or zoledronic acid and to initiate treatment earlier in the disease course rather than in a palliative setting.

    Q: Can you walk us through the key safety findings over this seven-year follow-up and kind of what you found?

    Bertrand Tombal, MD: So first I’ll explain why REASSURE was set up. OK, so REASSURE was set up shortly after the ALINA trial because when the data came, there was always that worry that when you use a radioactive compound that goes in the bone marrow of the patient, because that’s where bone metastases are, you could actually increase the rate of hematological malignancies. So that’s why initially REASSURE was done.

    So, the first conclusion is that REASSURE is reassuring. We don’t see a significant increase in the toxicity in the hematological toxicity of [Radium-223], so that was very important.

    And now it’s close to 1500 patients, so we’ve learned a lot about radium, and basically, we have learned 3 things. The first one is that, yes, the toxicity is hematological, but we rarely have dramatic toxicity like grade 4 or grade 5. Most of the toxicity is limited to grade 1 and grade 3, and it’s really reversible. The second one is linked to the first one to some extent, in that Radium-223 is not a drug that you should use too late as a kind of palliative care setting. If you do that, then you get the toxicity because this patient has bone marrow exhaustion, and you don’t get any therapeutic effect. So that’s something we learned, which is very important. Radium-223 is a drug that has to be given early to metastatic CRPC patients with bone metastasis. If you give it too late, that’s where you’ve got the toxicity, and you don’t have the effect.

    And then the third and very important observation is that indeed there is a toxicity, which is not necessarily to the molecule itself but to the fact that you’re tackling bone metastasis. So, if you tackle bone metastasis and you don’t protect your bones, you’re going to get a lot of fractures. There was confusion in the minds of the doctors because drugs like zoledronic acid and denosumab were developed to delay what we call skeletal-related events, which are basically complications of the cancer. When ALINA was published, it showed that it significantly delays [skeletal-related events], so the doctor would say, “No hurry. You don’t need to start this treatment soon.” What happens even with radiotherapy is that we have a lot of frailty and osteoporotic fractures, and you need to protect your patient with this. And so that’s the central message: if you’re using a drug that is heavily targeting the bone, the price to pay for the efficacy is an increased risk of bone fracture, and you absolutely need to combine Radium-223 with a bone-protecting agent.

    Is it disruptive? Is it new information? No, it’s been in the guidelines for 15 years. And actually, you could really summarize and say if you give Radium-223, please follow the guidelines. What do the guidelines say? Radium-223 is indicated in patients with metastatic castration-resistant prostate cancer and bone metastasis. The guidelines say zoledronic acid and denosumab should be given to anybody with metastatic CRPC and bone metastasis. So, no surprise, just comply with the guidelines.

    What is very interesting is all these messages from REASSURE actually resonate perfectly in the PEACE-3 trial, which is enzalutamide versus enzalutamide plus Radium-223, where we made absolutely the same observation. We haven’t seen any increase in hematological toxicity, and this is a randomized controlled trial.
    The toxicity is acceptable. We haven’t seen one single side effect increased by more than 5%, except we see a lot of fractures if we don’t give bone-protecting agents.

    So that’s what we learned from this REASSURE trial, the main message being if you believe in Radium-223, it’s not a treatment you give in a palliative care setting. You have to give it quite early. What we see also in REASSURE, not necessarily in the poster represented here, but in other publications, is that the earliest you give it, the higher the chance you’re going to give all 6 cycles. So that, in a nutshell, is the summary of the poster.

    Q: From the pharmacist’s perspective, what monitoring do you recommend when a patient is receiving this, especially given the data that you now have?

    Tombal: Clearly, 2 things. Any drug that could increase the hematological toxicity—that’s very important. And second, most importantly, because I realize in my hospital [pharmacists] play a critical role in ensuring that the patient is receiving both targeted agents. You know, it’s not listed as a typical drug-drug interaction, so pharmacy software will not pop up because basically if you look at drug-drug interactions, there are no interactions with Radium-223. But the pharmacist is central to making sure that at the time of the prescription of the Radium-223, there is a prescription for 1 bone-targeted agent. We know that in places where the pharmacist has involvement in that quality control monitoring, the rate of incorporation of bone-protecting agents was higher, so that’s very important.

    Q: Can you elaborate on how strong the association was between bone-protecting agents and reduced fracture risk, and what recommendations you would make about integrating these agents?

    Tombal: Yes. At [the European Association of Urology Congress] last year we published a subset analysis of the first patients who received or did not [bone-protective agents]. And we see that actually, if you take, for instance, [progression-free survival], radiographic progression-free survival, administering a bone-protecting agent was increasing PFS by 15 or 17 months. So, the benefit is huge. And if we look at Radium-223, it was very simple. When we look at the initial part when we didn’t make use of bone protection agents compulsory, in the enzalutamide regimen arm, the rate of fracture was close to 20%. What was interesting is that in the enzalutamide arm alone it was 10%.

    And when we administered the bone-protecting agent—in most cases it was denosumab, but zoledronic acid is good as well—we decreased that rate to 3% to 5%. So, my worry when we speak about Radium-223 and bone-protecting agents as a physician is that it’s not only when you give Radium-223; it’s every time your patient has bone metastasis and CRPC. So, my worry is that physicians say, “Oh, he doesn’t need radium, so he doesn’t need a bone-protecting agent.” No, the REASSURE data and the PEACE-3 data show this isn’t true.

    Basically, there is a separate message beyond the radium. It’s the importance of bone-protecting agents, whatever drug you receive.

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