Category Archives: Evolution

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Customer experience has evolved in exciting ways in the past few years. Michael Iacobucci, CEO at Interactions Corporation, cites two major reasons for this industry-wide evolution: the increasingly critical need for better customer experiences as a brand differentiator, and the AI advancement to enable those experiences. According to a recent survey, 75% of customers say they will pay more to do business with a company that provides good CX.

Exceptional customer service is not optional for todays businesses, Iacobucci said. In order to succeed, CX must be a top priority.

He added that along with the growing demand for better CX, technology has also evolved. Some of the major tech advancements for CX include improvements to AI, more sophisticated natural language processing and the introduction of voice assistants that can engage with customers in natural, human-like conversations.

The pandemic has only added fuel to the fire, Iacobucci said. Factors including labor shortages, increased customer uncertainty and the need for business continuity in a remote-first world only accelerated the adoption of these technologies, ushering us into a new era of CX.

Eighty percent of customers today say that the experiences companies provide are as important as their products or services, and customers are 2.7 times more likely to continue doing business with a company that provides high-quality service. Iacobucci spoke to Simpler Media Group about the changes the industry has experienced since 2008 and what he expects from the future of the industry.

Simpler Media Group: You've been in this industry for a long time more than 13 years at Interactions alone. Can you take us back to what the customer experience industry looked like when you first started, including the role technology was playing at the time?

Michael Iacobucci: The promise of the customer experience industry has been the same since my first day on the job: fast, effortless experiences for every customer, every time. But back in 20082009, companies were deploying technology that wasnt up to that task. The industry was riddled with limited dial menus, ineffective Intelligent Voice Response systems and speech systems masquerading as artificial intelligence but incapable of understanding, responding to or learning from customers. The goal was more often to deflect or contain customers, rather than to engage and serve them.

Take first-generation chat solutions and chatbots as an example. At the time, they were the shiny new object everyone had to have but not only was the technology not up to par, brands also implemented these solutions without thinking about how they would fit into a larger, cohesive customer experience strategy. Naturally, this approach soon disappointed and frustrated customers.

I knew as an industry, we could and should do better. I was intrigued by the potential for technology to reimagine the most frustrating experiences in our daily lives. And Im glad our team at Interactions stuck with it weve advanced leaps and bounds since then.

SMG: Are there places where this industry is still falling short? What can be done about this?

Iacobucci: Oftentimes, we still see AI and automation applied in a way that is not customer-centric. Take the rise of one-size-fits-all DIY solutions as an example. Companies are drawn to these options because they promise fast deployment and ease of use, but theres a lot more that goes into fostering excellent CX than throwing technology at the problem, including design and customization. Too often, these DIY solutions that promise to fix a companys CX are actually deployed at the expense of CX. Technology, even when its the latest and greatest, underwhelms when it isnt designed and deployed with the consumer in mind; it can only be impactful if it improves the user experience.

Were also seeing a lot of companies across this industry applying technologies like AI to incrementally improve the customer experience for agents, customers, or both from prompting agents on what to say next, to using AI to predict customer emotions. Theres nothing inherently wrong with this approach, but I often watch these companies and think theyre building on a shaky foundation like adding a fresh coat of paint or a snazzy new mailbox to a house thats bound to collapse due to a faulty foundation.

I believe weve pushed our existing CX paradigm about as far as it can go. Weve seen a lot of improvement in the last decade, but the moment for incremental improvement is past now. Its time for some fundamentally different thinking about how we can most effectively leverage the newest AI technologies, and [its time for us to] reimagine the relationship between AI and people to better serve our customers.

SMG: Can you elaborate on this redefined relationship between AI and people?

Iacobucci: AI and people both work best when they work together, and I dont see that changing, even in this new era of CX. But as call volumes rise, labor shortages stretch on, and customers become more irritable, AI can and should take on an even more prominent role to keep businesses running smoothly.

Companies can, for example, lead with AI to open and facilitate each conversation with customers. Many tasks from making a payment, to changing a billing address or scheduling an appointment can be done quickly and easily with AI. This allows customers to control their own journeys, taking care of matters on their own time and their own terms, 24/7, while taking some of the strain off overworked agents. With recent advancements, AI-powered solutions are capable of handling more than ever, and I think its time we let them.

SMG: What keeps you interested in this industry after more than a decade? What are you most excited for regarding what's to come?

Iacobucci: I said at the beginning that our industry has promised fast, easy, painless experiences for customers for more than a decade; Ive stuck around because we get a little closer every day. Today, I believe were at a real inflection point for the industry. The technology, investment, market maturity and demand are advancing in a way that allows us to deliver on this promise.

Im excited for the reality I see right around the corner. A reality where businesses are implementing an opti-channel strategy to provide customers with the best channel, for that moment in time and for the task at hand, so they can get their problem resolved quickly and painlessly. No repetition, no getting bounced around to multiple agents, no choosing from a restrictive dial menu just fast, easy resolution to questions and concerns.

Discover how Interactions can improve your CX technology stack at interactions.com.

Andie Burjek is a writer based in Chicago and a regular contributor to CMSWire.

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Inside the Latest Wave of Customer Experience Innovation or Evolution - CMSWire

For all the hype surrounding the creator economy, its a relatively new phenomenon, and even the multinational companies that have the most skin in the game are still trying to figure out where its all headed. In this sense, Zeev Farbman, co-founder, and CEO of Lightricks, is the exception.

Digital content creators have been able to earn a living since the rise of the internet, but many of the factors that make the creator economy what it is today have only been in play since 2020. With social distancing regulations in place, locked-down creators doubled down on posting original content and engaging with their audiences. As peoples values have changed, The Great Resignation has seen a shift towards self-employment, and with trust in companies diving, marketers have found increasing success tapping into the authenticity of influencers.

Founded in 2013 and today operating in high-growth mode following a $130 million Series D round with a $1.8 billion evaluation, Lightricks has made a name for itself as a developer of massively popular apps that help people to bring their visual content ideas to life. To date, the companys products, which include Facetune, Videoleap, Beatleap and Filtertune, have been downloaded over 500 million times.

We reached out to Farbman to get his take on what the future has in store for the creator economy and what creators need in order to thrive.

Zeev Farbman: We are working to lower the entry bar for creators, giving all creators access to our tools and services, and providing opportunities for them to quickly and easily connect with platforms or brands looking to collaborate on unique campaigns. We embrace the idea that anyone can be a creator, and strive to make our apps and services accessible to all creators across the spectrum.

The creator economy is rapidly evolving before our eyes, and things are going to change drastically especially with everything related to medium, and even small, creators. Influencer marketing is expected to reach some $15 billion in revenue during 2022, and marketeers are looking to work with the creators who have 100,000 followers or less.

What this means is that a new era is emerging for the middle class of content creators, but there are still obstacles to overcome especially questions of scale, which we at Lightricks are looking to overcome with new and innovative technologies.

Before 2020, the bigger influencers with massive followings on TikTok, Instagram or YouTube received most of the attention, but with the rapid creation, growth of complexity of online content in just the last two years, the market has opened up and offers great opportunity for those creators with smaller, loyal followers.

Empowering these growing, mid-sized creators is highly important, as this larger pool of creators will benefit by marketing their unique skills, talents and passions through photo and video content and more easily monetize through partnerships and brand campaigns.

Zeev Farbman: The day-to-day life of a CEO is different in a startup composed of five friends, a company of 50 working in the same building, and a company of 600 spread in four different countries and multiple time zones. And yet, the sense of excitement when something that was merely an idea becomes reality always remains the same, and its one of the most important things for me to see as a CEO.

Also, as a large company, I want every employee at Lightricks to feel like they are in a small startup, where their thoughts, ideas and work all matter and make a difference whether its by altering our roadmap, releasing a cool new feature to our users, or directing a successful new ad.

Lightricks is a company looking to enable creativity, create magic and bring ideas to life for millions and millions of people around the world, and I view that as part of our internal DNA too. To me, it is super important that the people behind the product are enjoying their journeys as well. When your employees can fully express themselves and use their strengths in a way that helps everyone, things run better and smoother.

Zeev Farbman: At Lightricks, we always enjoyed seeing how creative people use our tools. However, in recent years we saw these peoples mindset shift from amature or hobby towards more professional creators.

For instance, our user research taught us that while three years ago, 75% used our apps for friends and family, and only 25% viewed their creations as a source of income, today that has completely changed. Now, 75% of our users want to monetize their creative content, and only 25% use the apps as a friends and family hobby.

Now we want to continue to provide these creators with whatever tools and services they need as they drive the creator economy forward. We already had the creators engaged within our apps, and now it was about also helping and guiding them through the funnel, from creation to monetization.

The next step was finding a way to offer creators more monetization opportunities and how to support them. In March, we acquired Chicago-based Popular Pays, a platform that facilitates the collaboration between creators and brands on marketing and brand campaigns. This is the first step in our strategy to support and enable creators to reach their potential and monetize their talents and content.

The result is a platform that brings together our advanced tools and monetization opportunities for creators and gives brands access to the largest community of content creators across the globe. Our goal is to eventually integrate the platform directly with our apps, allowing creators to easily market their content while offering brands direct access to all the types of creators and content they are looking for.

Zeev Farbman: When we first introduced Facetune in 2013, social media was just embracing the power of the image and presenting the most impactful content that exemplified a creators passion, humor or artistry.

There are many trends worth tracking today, but two interest us a lot. The first is the increased use of short-form video, which is much harder to create than photo edits. As a result, creators are looking for insight from other creators on how best to leverage format or artistic effects to do so in their own content.

The second is creators understanding they can turn their hobby into a source of income, and as a result, they have new needs revolving around those monetization efforts.

Zeev Farbman: As the creator economy has evolved, its become clear that creators are the engagement drivers for the social media platforms. This has caused many interesting changes in the way both sides operate. Creators want to monetize their work, to be compensated for the value they give the platforms. At the same time, platforms want to ensure the creators stay on their network. so that the rest of the users get value from their browsing.

So yes, YouTube, Facebook, Twitter, TikTok and others are all playing the game, and we at Lightricks are prioritizing alignment with the interests of the creators, including the smaller and middle-sized ones. They can use our tools to export content to any platform they choose (at times, more than one), and we continue to build and provide them new and exciting monetization opportunities, so they can do what they do best create exciting and engaging content.

Have you read?Where Has All The Value GonebyBryan Gray.Is your Board stimulating or stifling innovationbyRosie Yeo.When It Comes to Business During Chaos, Only the Resilient SurvivebyRhett Power.Entrepreneur Trevor Edwards: How Collaboration Leads to Success.Everything You Need to Know About Adrien Rappoport.

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CEO Spotlight: Lightricks CEO Zeev Farbman on the Evolution of the Creator Economy - CEOWORLD magazine

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This is one of those bittersweet moments where I have the duty to share that our longtime editor Jake Slobe is stepping away from Clay & Milk to pursue other interests. Jakes been the primary news-sharer and storyteller of the Iowa entrepreneurial community for almost four years and we are all the better for his work. Personally, Im very happy for my friend Jake to have the opportunity to pursue other things while simultaneously being bummed about losing him from the Clay & Milk/Gravitate Coworking organization and our community overall.

This is Jakes last week as a full-time employee here but hes not going to disappear overnight. Hes agreed to stay on in a freelance capacity and help with the newsletter in the interim (woot!). Youll still see Jakes byline on stories (you can still email him tips and story leads at jake@clayandmilk.com) and were going to scale back the newsletter to three times per week rather than daily while we plan for the next evolution of Clay & Milk.

That evolution is the sweet part of an announcement like this, losing someone from the team who has been at the core forces us to put a real thought into what it is we do, how we can do it better and how we take things to a new level. Its the same thing weve done with every change in editor (were developing quite an alumni roster with Matt, Jami, Joey and now Jake!) weve had at Clay & Milk and its always exciting.

Do you have thoughts on what youd like to see in the next iteration of Clay & Milk? Id like to hear them (send a note!). While our mission to be the publication of record for all things tech, startup or entrepreneurial in Iowa wont ever change, how we go about always will.

Geoff WoodCo-Founder and Publisher

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The next evolution of Clay & Milk - Clay & Milk

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The evolution of employee time tracking from 1772 BC to today - Northwest Georgia News

Nature Timespiral: The Evolution of Earth from the Big Bang

Since the dawn of humanity, we have looked questioningly to the heavens with great interest and awe. Weve called on the stars to guide us, and have made some of humanitys most interesting discoveries based on those observations. This also led us to question our existence and how we came to be in this moment in time.

That journey began some 14 billion years ago, when the Big Bang led to the universe emerging from a hot, dense sea of matter and energy. As the cosmos expanded and cooled, they spawned galaxies, stars, planets, and eventually, life.

In the above visualization, Pablo Carlos Buddassi illustrates this journey of epic proportions in the intricately designed Nature Timespiral, depicting the various eras that the Earth has gone through since the inception of the universe itself.

Not much is known about what came before the Big Bang, but we do know that it launched a sequence of events that gave rise to the universal laws of physics and the chemical elements that make up matter. How the Earth came about, and life subsequently followed, is a wondrous story of time and change.

Lets look at what transpired after the Big Bang to trace our journey through the cosmos.

The Big Bang formed the entire universe that we know, including the elements, forces, stars, and planets. Hydrogen and massive dissipation of heat dominated the initial stages of the universe.

During a time span known as the Hadean eon, our Solar System formed within a large cloud of gas and dust. The Suns gravitational pull brought together spatial particles to create the Earth and other planets, but they would take a long time to reach their modern forms.

After its initial formation, the surface of the Earth was extremely hot and entirely liquid. This subsequent eon saw the planet cool down massively, solidifying some of the liquid surface and giving rise to oceans and continents, as well as the first recorded history of rocks.

Early in this time frame, known as the Archean eon, life appeared on Earth. The oldest discovered fossils, consisting of tiny, preserved microorganisms, date to this eon roughly 3.5 billion years ago.

The first era of the Proterozoic Eon, the Paleoproterozoic, was the longest in Earths geological history. Tectonic plates arose and landmasses shifted across the globeit was the beginning of the formation of the Earth we know today.

Cyanobacteria, the first organisms using photosynthesis, also appeared during this period. Their photosynthetic activity brought about a rapid upsurge in atmospheric oxygen, resulting in the Great Oxidation Event. This killed off many primordial anaerobic bacterial groups but paved the way for multicellular life to grow and flourish.

The Mesoproterozoic occurred during what is known as the boring billion stage of Earths history. That is due to a lack of widespread geochemical activity and the relative stability of the ocean carbon reservoirs.

But this era did see the break-up of the supercontinents and the formation of new continents. This period also saw the first noted case of sexual reproduction among organisms and the probable appearance of multicellular organisms and green plants.

In some respects, the Neoproterozoic era is one of the most profound time periods in Earths history. It bookends two major moments in the planets evolutionary timeline, with predominantly microbial life on one side, and the introduction of diverse, multicellular organisms on the other.

At the same time, Earth also experienced severe glaciations known as the Cryogenian Period and its first ice age, also known as Snowball Earth.

The era saw the formation of the ozone layer and the earliest evidence of multicellular life, including the emergence of the first hard-shelled animals, such as trilobites and archaeocyathids.

The Paleozoic is best known for ushering in an explosion of life on Earth, with two of the most critical events in the history of animal life. At its beginning, multicellular animals underwent a dramatic Cambrian explosion in aquatic diversity, and almost all living animals appeared within a few millions of years.

At the other end of the Paleozoic, the largest mass extinction in history resulted in 96% of marine life and 70% of terrestrial life dying out. Halfway between these events, animals, fungi, and plants colonized the land, and the insects took to the air.

The Mesozoic was the Age of Reptiles. Dinosaurs, crocodiles, and pterosaurs ruled the land and air. This era can be subdivided into three periods of time:

The rise of the dinosaurs began at the end of the Triassic Period. A fossil of one of the earliest-known dinosaurs, a two-legged omnivore roughly three feet long-named Eoraptor, is dated all the way back to this time.

Scientists believe the Eoraptor (and a few other early dinosaurs still being discovered today) evolved into the many species of well-known dinosaurs that would dominate the planet during the Jurassic period. They would continue to flourish well into the Cretaceous period, when it is widely accepted that the Chicxulub impactor, the plummeting asteroid that crashed into Earth off the coast of Mexico, brought about the end of the Age of Reptiles.

After the end of the Age of Dinosaurs, this era saw massive adaptations by natural flora and fauna to survive. The plants and animals that formed during this era look most like those on Earth today.

The earliest forms of modern mammals, amphibians, birds, and reptiles can be traced back to the Cenozoic. Human history is entirely contained within this period, as apes developed through evolutionary pressure and gave rise to the present-day human being or Homo sapiens.

Compared to the evolutionary timeline of the world, human history has risen quite rapidly and dramatically. Going from our first stone tools and the Age of the Kings to concrete jungles with modern technology may seem like a long journey, but compared to everything that came before it, is but a brief blink of an eye.

*Editors note: An earlier version of this article contained errors in the header graphic and an incorrect citation, and has since been updated.

This article was published as a part of Visual Capitalist's Creator Program, which features data-driven visuals from some of our favorite Creators around the world.

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Nature Timespiral: The Evolution of Earth from the Big Bang - Visual Capitalist

While every hotel customizes its offerings, one thing is abundantly clear contactlessguest experiences are here to stay.

Technological advancements were inevitable, and the pandemic gave hoteliers time to analyze and determine how technology could be best incorporated to overcome the challenges. All major hotel brands as well as independents now encourage guests to download their mobile apps which includes several features empowering them to get what they need and manage amenities with minimal human contact. While some features like contactless check-in and check-out, ordering food from the on-site restaurants, communicating with the front desk, or cashless payments are common, many apps have unique, customizable options.

Alma Resort, the independently owned and operated resort in Vietnams Cam Ranh peninsula, has launched the Alma Resort App, which offers menus, promotions and vouchers, as well as live stream broadcasts and information about events and COVID-19-related health and safety tips. Since Cam Ranh gets around 300 sunny days a year and is known for having Vietnams best weather, the hotel is planning to add a weather cam in real time that can be accessed on the app.

The app, which was put forward in a heads-of-department meeting by the resorts executive chef, was created by the hotel team within two months, said Almas Managing Director Herbert Laubichler-Pichler. Unlike major chains, the independent hotels always have to navigate technological change themselves as they dont have a head office to develop or recommend the latest equipment and software, Laubichler-Pichler said. And this can be difficult for the independent hotels when their staff on the ground such as, for example, the front office managers, are the users of the technology but are preoccupied with the guests and prioritizing their needs.

The good news, saidLaubichler-Pichler, is that the technologies required to power these apps is not expensive. As an independently owned and operated hotel, Alma Resort had the autonomy to invest in the app and develop it themselves which helped keep costs under control. The app cost no more than US$5,000 to develop. These technologies are not expensive; you dont have to spend hundreds of thousands of dollars. You also need to ensure that the technology is set up in a way so that it is not a money pit; you dont want to be continually spending a lot of money with a third-party every time you need to make an update to the app. You can realize ROI in many ways quite quickly after launching an app.

In spring 2021, Aqua-Aston Hospitality, Honolulu, Hawaii, introduced an app with an intelligent messaging platform in more than 20 of its managed hotels and resorts across Hawaii. It allows guests to communicate with associates in real-time without having to call or visit the front desk. For example, guests can send a message to the front desk about their arrival time and get information about guest amenities. Among other things, they can receive a copy of their folio, get fresh towels or arrange housekeeping service.

Since Aqua-Astons app uses text messaging system as a mode of communication between guests and associates, building the app was surprisingly affordable and utilizes a mode of communication that we all use in everyday life, said Mark DeMello, vice president of operations, Aqua-Aston Hospitality.

Besides providing remote check-in, mobile key, options to order food, temperature control, self-check-in and mobile payment methods, Virgin Hotels Lucy app also integrates the in-room entertainment system to provide casting, allowing guests to use their smartphones as the TV remote. Launched in 2015, the updated app now offers secure ID verification, cashless tipping facility, in-room lighting controls and access to custom fitness routines.

While guests at citizenM already had access to digital solutions like a check-in kiosk and an iPad to control their room settings before the pandemic, the introduction of a guest app during the pandemic across all its hotels has been a success and resulted in the highest guest satisfaction and most loyalty among the app users, said citizenM Hotels Chief Digital & Experience Officer Casper Overbeek.

Every day we see new opportunities, not because of tech, but because we want to adapt to customer needs, Overbeek said. We have launched a new paid subscription service. Our customer research showed that price security and availability are key pain points for the frequent traveler. With our new membership mycitizenM+ we solve those.

Charlestowne Hotels, Charleston, South Carolina, which was using contactless technology long before it became such an integral part of the industry, sends out a pre-registration email with an option for guests to add room requests or notes, a follow up email when the room is ready and a text message or email which contains the room key. A similar process takes place at checkout, where a folio can be reviewed electronically, charges confirmed and guest feedback submitted. Elaborating on the Charlestownes technological innovations, Director of Technology Max Spangler said in-room IoT devices, like Amazon Echo and Google Nest Hub, double up as virtual concierge as they are enabled to answer questions and streamline guest requests to appropriate departments.

The pre-arrival registration process has been the most popular and engaging with our guests. Automated guest communication and reservation management has also been well received, Spangler said.

Besides fulfilling the new-age travelers need for reduced human contact, these apps have helped reduce labor costs, especially at a time when the industry has been grappling with a severe labor crisis. The real benefit of contactless technology, Spangler said, is that it allows them to be more flexible with their staffing model.

We can be more agile when it comes to staff placement, hours worked during a shift, and hire a wider range of employees with skills that reach beyond knowledge for a particular method or system, Spangler explained. Flexibility for our team members, in a labor market as competitive as this, is paramount.

The technology also helps make staffs more productive, improve efficiency, and remove some of the mundane, repetitive tasks. At Charlestowne Hotels, the pre-arrival registration helps reduce phone volume and mobile key and text communication allows them to drastically reduce peak check-in times and corresponding volume.

When guests do arrive and decide to check in at the desk, our teams are fresher and more engaging with our guests than had they just managed a long queue of guests, Spangler added.

Besides the labor costs, a mobile key solution has also helped reduce other hard costs, like key cards. Spangler said integrating more contactless tech into Charlestowne hotels has resulted in an uptick in guest satisfaction and increased employee happiness. When we evaluate the contactless technology, the ROI is analyzed from the guest perspective are guests engaged and loyal, are guest scores up, is staff happier? Those are the items we quantity versus the costs of tech implementation.

For smaller and independent hotel brands like Alma Resort, it has been challenging to encourage guests to switch to the apps and use its features as many of them are still not used to the technology.

Our staff have spent a lot of time urging guests to download the app and helping to ensure that guests have downloaded it correctly, Laubichler-Pichler said.

With reduced travel and on-site presence due to lockdowns and travel restrictions, it has been difficult during the pandemic to implement all the emerging components of guests demands, said VirginHotels Vice President of Technology Jason Doebrich. At the same time, due to labor constraints and turnover, training on the new technologies and procedures has also been difficult. Supply chain issues have led to long lead times and delays on parts and resources, Doebrich added.

No more front desk?

Despite the proliferation of technology, hoteliers feel the hotel lobby can never be rendered redundant. Guests will still need and prefer access to a human and not a robot or an app to ask questions. Hotel apps can be cost-effective and convenient for travelers, but many guests will still want to sit in a restaurant and consult the waiter for the best available options before ordering a dish off the menu.

A warm greeting and a smile on arrival to a hotel are hallmarks of good old-fashioned hospitality, Laubichler-Pichler said. I think that the personal touch will further distinguish the high-end hotels from the budget ones in future.

Hotel lobbies still serve their purpose for guests who want a personal, high-touch experience. Irrespective of guests seeking a physical presence or a virtual one, Aston-Aquas front desk teams assist guests with their needs, DeMello said. The recently renovated lobby and refreshed arrival experience at our luxury condominium property, Aston Waikiki Beach Tower, provides guests with an enjoyable in-person check-in and check-out process. We installed two-sit down front desks and welcome guests with a sustainable strand shell lei, in addition to a cold Oshibori towel and glass of fresh juice.

Terming the apps as extra tools provided to team members and guests, Doebrich said the front desk is still widely used by many guests as the technologies are still in their formative years.

Technology is merely an enabler for creating a greater experience at citizenM hotels, Overbeek said. While the pandemic accelerated the digital innovations, it has also made the hotel industry aware of how much they need human touch. While citizenM guests have been checking in through check-in kiosks from the very first day, there is always an citizenM ambassador to welcome and help where needed, he explained. This will never change as it is key to our brand experience. We do study how we will further optimize the check-in experience through our app, but the welcoming smile will always be there.

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Evolution of the guest app HOTELSMag.com - HOTELS

Image source: Discovery Institute.

Magnetotactic bacteria are the fascinating stars of the new episode ofSecrets of the Cellwith Michael Behe, which premieres TODAY at 5 pm Pacific time/8 pm Eastern right here. These bugs could point the way to a treatment for cancerous tumors, thanks to their natural ability to maneuver by sensing the Earths magnetic field. Dr. Behe explains how. They owe this gift to a sophisticated manufacturing and quality-control process a code-driven factory, in effect, in each bacterium for the production of magnetosomes, forming the functional equivalent of a compass. A modern, human-built factory would be no less sophisticated.

Its true, says Behe,

some types of bacteria are harmful to humans. But countless others are superheroes of the microbial world. All this raises an obvious question. How did bacteria come to be so diverse and so ingenious?

Indeed, thats the question, and he details the steps that an unguided process would have to take to furnish these bacteria with the needed equipment. An intelligent agent with foresight and a plan could do it, step by step. But blind Darwinian evolution? Color me skeptical, says Professor Behe, a biochemist at Lehigh University and pioneer in the field of intelligent design.

Join us here as we learn about this and other micro-scale wonders that surely would have given Charles Darwin cause for reflection if he had known about them.

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Behe: Magnetotactic Bacteria and Other Micro-Wonders - Discovery Institute

Plenty has changed in the head and neck cancer field in the past 10 years. This time has allowed for key PD-1 inhibitors to gain FDA approval, de-intensification to come into the fold, and specifically, staging for human papillomavirus (HPV) status has evolved to aid oncologists in their prognosis.

Although there have been several negative trial results in recent larger studies, they have been hypothesis generating and have answered significant questions for the treatment of head and neck cancers. Going forward, they may help to generate practice-changing data and improve treatment options for the next 10 years.

In an interview with Targeted Oncology, Robert L. Ferris, MD, PhD, FACS, director, UPMC Hillman Cancer Center; Hillman Professor of Oncology; associate vice chancellor for cancer research; co-director for the Tumor Microenvironment Center; professor of otolaryngology, immunology, and radiation oncology, University of Pittsburgh; and co-physician editor in chief of Targeted Therapies in Oncology, elaborated on the significant progress in the head and neck cancer space, as well as potentially practice-changing results that will come with emerging agents, for Head and Neck Cancer Awareness Month.

Targeted Oncology: How has the field of head and neck cancer changed over the past 10 years?

Ferris: If you go back 10 years ago to 2012cetuximab [Erbitux] was felt to be just as effective as cisplatin. The RTOG 1016 [NCT01302834] study shows that's not the case.1 There's a superiority of [chemotherapy] over cetuximab for locally advanced disease. We had no FDA-approved PD-1 inhibitors, [but in the past 10 years] nivolumab [Opdivo] and pembrolizumab [Keytruda] are standard in second line and first line. We have the concept of de-intensification of therapy for good prognosis. HPV-positive disease [research] was getting started, and whether that was safe, and how to do that was launching clinical trials. The ECOG 3311 trial [NCT01898494] that we published a couple months ago,2 was just being designed in 2011 or 2012. The concept of de-intensification for HPV-positive, good-prognosis disease was a concept that was tested for the past 10 years, and is now beginning to show clinically relevant, practice-changing data to guide what the appropriate treatment intensity is for this new disease. I think we understood that HPV was a major and increasing subset 10 years ago. We understood that it had a better prognosis but had no impact on treatment. And in the past 10 years, the staging system AJCC [American Join Committee on Cancer] 8 came out,3 which changed the staging system and separated by HPV status. We began having de-intensification clinical trial results, which was just kind of a concept 10 years ago. I think [there has been] pretty substantial progress in 10 years. They have totally new and standard therapies for a good prognosis group of patients and have totally new FDA-approved agents in recurrent metastatic disease, but so far, we don't know how to use it in locally advanced disease.

De-intensification is here. Staging is here now based on HPV status, a different staging system, which didn't exist before. We used to stage it all the same, but now there's HPV-negative and HPV-positive staging, which is separate. Immunotherapy is approved, and cetuximab is inferior to cisplatin in locally advanced disease, though they were felt to be interchangeable 10 years ago.

What trials have been the most practice changing in recent years, and what do you think will be the next wave of practice-changing data?

There are the CheckMate 141 [NCT02105636] and KEYNOTE-048 [NCT02358031] trials that got PD-1 inhibitors, nivolumab and pembrolizumab, approved in the second line and the first line.4,5 [There is] RTOG 1016 for [chemoradiation for] locally advanced disease for non-surgical treatment of HPV-positive head neck cancer and then ECOG 3311 for transoral robotic surgery as de-intensification. I'd say those are probably the biggest. You could say, from a negative standpoint, that the JAVELIN 100 trial [NCT02952586],6 which showed no benefit of adding avelumab [Bavencio] in locally advanced disease wasn't practice changing, but it was impactful because the expectations were high. There is still pembrolizumab added to chemoradiation. [We are waiting for] the KEYNOTE-412 [NCT03040999] trial results, which was designed for high-risk locally advanced disease,7 like JAVELIN, to be reported. You could say that the phase 3 CheckMate 651 trial [NCT02741570],8 which was reported at ESMO [European Society for Medical Oncology], showed that nivolumab and ipilimumab [Yervoy] did not beat the EXTREME regimen [cetuximab, cisplatin/carboplatin, and fluorouracil followed by cetuximab maintenance] like the KEYNOTE-048 trial showed that pembrolizumab did alone. I think that was more of a trial design flaw than it was that nivolumab and ipilimumab doesn't work.

I would say the ones that are affirmative results that have changed practice are the CheckMate 141 and KEYNOTE-048 trials for the PD-1 inhibitors, RTOG 1016, showing superiority of cisplatin, and then the use of transoral robotic surgery, ECOG 3311, permitting omission of chemotherapy and reduced-dose radiation for surgically treated HPV-positive patients.

Obviously, I have a conflict of interest as I've been involved in a couple of those trials. But I think, if you asked someone who was not Bob Ferris, that they would say the same things.

What are some of the new targets that are of interest for the future of head and neck cancer?

In IO [immune oncology], LAG-3 inhibition has recently been approved for melanoma,9 and there's some promising data in head neck cancer. So, I think LAG-3 combined with PD-1 will be intriguing.

I don't know if CTLA-4 is dead. I think it's an active agent. It would be great to see some role for CTLA-4 targeting head and neck cancer. We've published on that recently and have a neoadjuvant trial in it.10 I think the [CheckMate 651 trial] was not as negative. It just barely missed and had great durability. So CTLA-4 and LAG-3 may still be pursued. LAG-3 is earlier in its development. The SMAC mimetic agent, xevinapant, that was [previously] called Debio 1143, is pretty promising and is being used on top of chemoradiation or in place of chemotherapy. So, xevinapant for particularly p53-mutated [malignancies is of interest].

PI3 kinase inhibitors have been pretty disappointing, despite the relatively frequent presence of activating PI3K alterations. I think the field would love to see that because we don't have a lot of oncogene activation, but PIK3CA is present, and yet the PI3 kinase inhibitors don't really seem all that active, particularly not in the mutated ones. The role of circulating tumor DNA, particularly for HPV-positive disease, which dovetails into the next phase of de-intensification, is actually monitoring tumor burden. I think that's an intriguing concept that is not a new target, but I think it's conceptually innovative.

What role would you say that drug sequencing of these therapies plays in head and neck cancer currently?

We think it matters now in the reverse way that we thought it mattered. It's sort of like the RTOG 91-11 trial [NCT04943445] for larynx cancer.11 That trial compared cisplatin chemoradiation given concurrently vs induction chemotherapy followed by radiation. If you looked at the early results, concurrent chemoradiation was the best at 2 years. That was the New England Journal of Medicine paper that Arlene A. Forastiere, MD, published in terms of preserving the larynx.12 If you follow down the road, because concurrent chemoradiation was so toxic, eventually the overall survival was better to give chemotherapy first and separate it from radiation. In the case of IO sequencing, IO therapy, again, the JAVELIN trial was designed concurrently, before, during, and with a year of maintenance of avelumab because the preclinical data seem to suggest that just giving IO separate before or after radiation or chemoradiation would not harness the synergy that now we think there's some biology and that it's actually potentially deleterious to give avelumab during chemoradiation because of the impact of it on the immune system.

We now have lung data from the PACIFIC trial [NCT02125461],13 showing that you can take a high-risk group after chemoradiation, give a year of durvalumab [Imfinzi], and they do fantastic. That analogous trial, called IMvoke010 [NCT03452137],14 giving atezolizumab [Tecentriq] after high-risk treated head and neck cancer, should report any time. Were all enthusiastic because since JAVELIN failed, that must mean that IMvoke010 will be positive. You say sequencing, I might say separation of concurrent agents, both of which have activity. We know that PD-1 and PD-L1 inhibitors work, and we know that chemoradiation works. So why, when you put them together, do you not get an added benefit, unless there's some interaction? If you go back to just treat with 1 and then treat with the other, you should get this plus that in terms of activity.

We have our oral abstract at ASCO [American Society of Clinical Oncology]. By pure coincidence, luck, and maybe a little bit of knowledge of the field, we designed a trial here, a relatively small, randomized, phase 2 trial that was just 40 mg/m2 or so in each arm of chemoradiation, concurrent with pembrolizumab or chemoradiation alone followed by pembrolizumab concurrently vs sequentially. Now that we know the JAVELIN trial failed results, we broke the code and put it in for ASCO, and the sequential data look better. This was started in 2015. We designed this trial so it started out as a biomarker trial [with 20 patients] in each arm, and I went back to Merck and got it doubled so we could at least look at some clinical end points. The 1-year progression-free survival rate, and we're getting 2-year and 3-year [progression-free survival rates], looks like sequentially separating them is better than concurrent treatment. We do think sequencing matters.

Currently, 2 immunotherapy agents are approved in HPV-positive and -negative related head and neck cancer. Can you address some of the research that is looking at immunotherapy in the definitive treatment setting in patients who don't have metastatic disease?

At present, there's no approved role for IO. There are trials using it in the pre-treatment stage, usually preoperatively: neoadjuvant for a month to 6 weeks, a single agent or in combination. There are post operative for post treatment with a year of maintenance that ECOG has, EA 3191 [NCT04671667].There are various trials testing in the local advanced setting, but none of them have shown any positive data yet that IMvoke010 already talked about. There's no role in the locally advanced setting for IO therapy outside of a clinical trial.

What are some of the emerging biomarkers in head and neck cancer that researchers are watching?

I would say that most folks are very enthusiastic. We've essentially failed adding anything to standard chemoradiation, and so this concept of xevinapant, adding a SMAC to a DNA damage pathway inhibitor [is promising]. The phase 2 data were very positive and very promising, and it wasn't by a little bit.15 You always expect a little fall off [in the curves] when you go to a phase 3, but this was a big enough phase 2, and it's substantially beneficial that I think the enthusiasm is there and there's a phase 3 running [NCT04459715]. I would say that folks are looking at that. There's also continued efforts at de-intensifying for HPV-positive disease in some ways, continuing to reduce radiation. There was an ASTRO [American Society for Radiation Oncology] with 36 Gy of radiation as opposed to the 50 Gy that we had in ECOG 3311. There's use of circulating tumor DNA to reduce adjuvant therapy. I think getting a little bit more personalized in selecting the best patients who are candidates for reduced doses and then finding ways to intensify therapy for the poor-prognosis HPV-negatives is a key area where we've made no progress in a few decades.

What would you say more community oncologists should know about how to treat head and neck cancers?

HPV is continuing to increase in frequency, primarily in the tonsil and the base of tongue. P16 is the surrogate biomarker to test for it, but don't use p16 unless the tumor is from the base of the tongue or the tonsil. It doesn't work in the oral cavity or the larynx, and we see community oncologists thinking that you just get p16 on every cancer of the head and neck. No. It's only a surrogate in the tonsil or base of tongue primary tumors. Also, you can get it from a neck needle biopsy so it can be useful to localize the primary tumor to the tonsil or the base of the tongue. [I want them to] know it does appear safe for good prognosis [for patients who are] HPV-positive to reduce the radiation and chemotherapy dose. National Comprehensive Cancer Network guidelines are being updated with that. PD-L1 testing is not required for second-line IO therapy, but it is helpful and required in the first line to decide whether to give pembrolizumab monotherapy or pembrolizumab plus chemotherapy. And at present, adding IO in the locally advanced setting does not have a role.

References

1. Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial [published correction appears in Lancet. 2020 Mar 7;395(10226):784]. Lancet. 2019;393(10166):40-50. doi:10.1016/S0140-6736(18)32779-X

2. Ferris RL, Flamand Y, Weinstein GS, et al. Phase II randomized trial of transoral surgery and low-dose intensity modulated radiation therapy in resectable p16+ locally advanced oropharynx cancer: an ECOG-ACRIN cancer research group trial (E3311). J Clin Oncol. 2022;40(2):138-149. doi:10.1200/JCO.21.01752

3. Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more personalized approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-99. doi:10.3322/caac.21388

4. Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab vs investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol. 2018;81:45-51. doi:10.1016/j.oraloncology.2018.04.008

5. Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915-1928. doi:10.1016/S0140-6736(19)32591-7

6. Lee NY, Ferris RL, Psyrri A, et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021;22(4):450-462. doi:10.1016/S1470-2045(20)30737-3

7. Machiels JP, Tao Y, Burtness B, et al. Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Future Oncol. 2020;16(18):1235-1243. doi:10.2217/fon-2020-0184

8. Argiris A, Harrington K, Tahara M, et al. Nivolumab (N) + ipilimumab (I) vs EXTREME as first-line (1L) treatment (tx) for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Final results of CheckMate 651. Ann Oncol. 2021;32(suppl_5):S1283-S1346. doi:10.1016/annonc/annonc741

9. FDA approves first LAG 3 inhibitor antibody Opdualag for metastatic melanoma. News release. BioSpace; March 22, 2022. Accessed April 25, 2022. https://bit.ly/3KgqB65

10. Jie HB, Schuler PJ, Lee SC, et al. CTLA-4 regulatory T cells increased in cetuximab-treated head and neck cancer patients suppress NK cell cytotoxicity and correlate with poor prognosis. Cancer Res. 2015;75(11):2200-2210. doi:10.1158/0008-5472.CAN-14-2788

11. Forastiere AA, Zhang Q, Weber RS, et al. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013;31(7):845-852. doi:10.1200/JCO.2012.43.6097

12. Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003;349(22):2091-2098. doi:10.1056/NEJMoa031317

13. Faivre-Finn C, Vicente D, Kurata T, et al. Four-year survival with durvalumab after chemoradiotherapy in stage III NSCLC-an update from the PACIFIC trial. J Thorac Oncol. 2021;16(5):860-867. doi:10.1016/j.jtho.2020.12.015

14. Wong D, Fayette J, Guo Y, et al. Abstract CT123: IMvoke010: Randomized Phase III study of atezolizumab as adjuvant monotherapy after definitive therapy of squamous cell carcinoma of the head and neck (SCCHN). Cancer Res. 2019;79(13_supplement):CT123. doi:10.1158/1538-7445.AM2019-CT123

15. Bourhis J, Sun X, Le Tourneau C, et al. 3-years follow-up of double-blind randomized phase II comparing concurrent high-dose cisplatin chemo-radiation plus xevinapant or placebo in high-risk patients with locally advanced squamous cell carcinoma of the head and neck. Ann Oncol. 2020;31(suppl_4):S1142-S1215. doi:10.1016/annonc/annonc325

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Head and Neck Cancer Treatment Evolution Leads the Way for Future Developments - Targeted Oncology

The World Health Organizations (WHO) director-general is pressing countries to maintain COVID-19 surveillance and share information on its transmission and sequencing, saying reduced testing abroad makes us increasingly blind to patterns of transmission and evolution.

Speaking on Tuesday during a press conference, WHO Director-General Tedros Adhanom Ghebreyesus noted that while COVID-19 cases and deaths continue to decline, the world needed to welcome the news with some caution.

This makes us increasingly blind to patterns of transmission and evolution. But this virus wont go away just because countries stop looking for it. Its still spreading, its still changing, and its still killing, Tedros said.

The threat of a dangerous new variant remains very real and although deaths are declining, we still dont understand the long-term consequences of infection in those who survive, he added. When it comes to a deadly virus, ignorance is not bliss. WHO continues to call on all countries to maintain surveillance.

The development comes as White House officials have pressed for more money to be authorized by Congress for pandemic funding, though lawmakers have not been able to strike a deal yet.

During his first appearance speaking to reporters in the White House briefing room, COVID-19 response coordinator Ashish Jha on Tuesday warned that durable and effective vaccines potentially ready for the fall and winter as well as new, effective treatments could be jeopardized if administration officials are unable to secure more money for COVID-19.

The bottom line is that none of us can predict with any certainty where exactly this pandemic is going, what the virus is going to do next. All we can do is prepare. And thats what we need Congress to do, is to help us prepare and be ready for whatever eventuality comes, Jha said.

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WHO chief: World is 'increasingly blind' to COVID transmission, evolution - The Hill