Daily Archives: February 11, 2022

Expedia Group is still very much caught up in making over the company. Is it working? Company officials are basically telling Wall Street trust us, we think this is going to be good.

Dennis Schaal

Expedia Group, in releasing its fourth quarter earnings Thursday, saw plenty of cause for optimism, but as far as quantifying its progress in terms of its two-year-old restructuring and rebuilding drive, the message was youll have to wait until the travel industry reverts to a semblance of normal to quantify the progress.

While rival Airbnb, which reports fourth quarter earnings next week, basks in its brand awareness and proclivity in attracting bookers directly, Expedia Groups selling and marketing expense line in the fourth quarter was 45.8 percent of revenue. Selling and marketing expense climbed 106 percent to more than $1 billion.

Commenting on Expedia Groups push to render its marketing efforts more efficient, CEO Peter Kern said during a call with analysts: So the short answer is, we made a huge amount of progress, as I said, in terms of tools, in terms of data, in terms of insights, in terms of being able to test and learn across a much broader swath of our enterprise. But being able to quantify really how much better it is in basis points or something that would give you a projectable marketing efficiency is still very challenging.

For the past two years, Expedia Group has been reorganizing the internal workings of the company, combining brand teams that previously may have worked at cross-purposes, shedding brands that werent core to the company, and trying to consolidate its tech stack. The company entered 2022 with 10,000 fewer employees than at the end of 2019.

The company is currently revamping all of its loyalty programs, and intends to unify them into one plan. Kern said he thought that work would take most of 2022, and that 2023 would be the year where the company sees the first financial benefit.

So I think we feel good about the technical progress the teams are making about the way theyve plotted out their course of learning and testing, Kern said. And theres no question it will inure to our benefit. But being able to identify a single thing or a single win or how to quantify it is really hard to do at this moment. So I think you have to wait for the collective good to roll through our P&L (profit and loss statement), and hopefully, youll see it as things develop.

In a Skift interview following the call with financial analysts, Kern pointed to a service platform, which includes voice chat, and enables people to self-service as an example of some of the behind the scenes progress the company is making. We have been essentially training it with skills across the entire company to serve traveler problems, supplier problems, all kinds of things, he said.

Kern said it while it makes the company more efficient, more importantly travelers appreciate it and have a better experience.

Expedia Groups revenue in the fourth quarter still tracked considerably lower than in the comparable period in pre-pandemic 2019. Its revenue mark of around $2.3 billion in the fourth quarter of 2021, was 17 percent lower than the same period two years ago. However, that $2.3 billion stood 148 percent higher than the fourth quarter of 2020.

Expedia Groups lodging revenue in the fourth quarter climbed 116 percent year over year to $1.7 billion.

Expedia Group recorded $276 million in net income in the fourth quarter of 2021, reversing a $412 million loss a year earlier. The company said that was driven by room night growth and, to a lesser degree an increase in average daily rates.

For full year 2021, Expedia Group narrowed its year over year loss by 90 percent to $269 million in the red. Revenue for the year grew 65 percent to $8.6 billion.

Selling and marketing expense climbed 106 percent to more than $1 billion. Selling and marketing expense was 45.8 percent of revenue.

While we experienced yet another significant travel disruption from Covid this quarter, we were pleased to see thatthe impact was less severe and of shorter duration than previous waves, Kern said in a statement as part of the fourth quarter earnings announcement. Notably, the travel industry and traveling public prove more resilient with each passing wave, and we continue to expect a solid overall recovery in 2022, barring a change in the trajectory of the virus.

Expedia Group Chief Financial Officer Eric Hart said the companys vacation rental brand Vrbo is showing strength compared with 2019 and 2021, and it continues to win share, as well without providing specifics. He said the hotel recovery has lagged Vrbos trajectory.

But Kern said Vrbo is not seeing a trend toward long-term stays that others namely Airbnb are seeing. He said if people have more flexibility and can spend more days on vacation, then that would be terrific and a tailwind, but that hasnt benefited Vrbo to date.

In the Skift interview after the analyst call, Kern said Vrbo was never in the business of by and large of offering two-night stays. So its vacation rental brand, which is geared primarily toward families and other groups in resort areas, is indeed seeing stays getting elongated, but not to the extent that it is seeing a surge of bookings for 30-day stays or longer.

Kern said Expedia Group is committed to continuing the restructuring process, and making the company more efficient so it can better stimulate and capture demand, and wont engage in mergers and acquisitions activity just because there are good deals out there.

Were going to buy things that fit our long-term strategy to drive where were trying to drive it if we buy it, he said.

Update: The story has been updated to add some information from CEO Kern about a new service platform for travelers and suppliers that Expedia is introducing across the company, and about trends at its Vrbo unit.

The rest is here:

Expedia: Youll Have to Wait Longer to See Hard Data on Our Rebuild Progress - Skift

Cincinnati tight end C.J. Uzomah tried to send a message that he wouldnt miss the Super Bowl by taking the brace off his left knee and tossing it behind him onto the Bengals logo during a pep rally.

His coach said Wednesday hes optimistic about Uzomahs progress even as the Bengals kept the tight end out of practice.

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Zac Taylor says Uzomah likely will work at practice Thursday with the Bengals taking advantage of having three days of work left to see where the veteran is. Uzomah played only nine snaps in the AFC championship game before hurting his knee. He caught 49 passes for 493 yards and five touchdowns in the best season of his career, and he has 13 catches for 135 yards this postseason.

"Again, optimistic with where hes at," Taylor said. "Team has handled it really well. We try to keep our scheduling as consistent as possible. And you know, so were midway through our first day here, and our guys have handled it really well."

Cincinnati Bengals tight end C.J. Uzomah reacts during the Super Bowl LVI Opening Night Fan Rally, Monday, Feb. 7, 2022, in Cincinnati. (AP Photo/Jeff Dean)

PRINCES RETURN

Isaiah Prince has no regrets about the difficult decision he made last season.

Opting out because of the coronavirus pandemic still wasnt easy for the Cincinnati Bengals offensive tackle.

"Of course, I was very hurt," Prince said. "I believe that was probably one of the most trying times in my life. Looking back at my career, I dont think Ive ever really missed a game, a practice not in college.

"So for me, missing my first season (with the Bengals), that was kind of devastating for me."

Prince was drafted by Miami in the sixth round in 2019 out of Ohio State and played in four games, including two starts, as a rookie. He was waived late that season and claimed by Cincinnati a day later.

The 6-foot-7, 305-pound offensive lineman was considered a potential depth piece to help protect then-rookie quarterback Joe Burrow. But the pandemic caused Prince to reassess things at home, and he decided to not play in his first year with the Bengals.

"Being at home while I opted out, just watching, I mean, Im human," he said. "There were times I was wondering, you know, how am I going to get back in? But I stayed faithful and kept believing in myself."

Prince, whose Bengals teammate Josh Tupou also opted out, went back to school during the year away from football and finished his undergraduate degree at Ohio State. He used boxing to help him train and also worked out at LeCharles Bentleys O-Line Performance facility in Arizona.

Prince returned to the Bengals this season, made the roster out of training camp and took over as the starting right tackle when Riley Reiff was lost for the season with an ankle injury in December. And now Prince is preparing to start in the Super Bowl.

"Those times definitely helped prepare me for this moment and staying focused regardless of whats going on around me," Prince said. "I think that was a very challenging time in my life, but I still had to wake up every day and stay focused on the things that really needed my attention. That definitely plays a key part in right now with everything thats going on, is just staying focused and controlling what you can control."

NINE ON NINE

Carson Palmer is hopeful that the Bengals have enough to beat the Rams on Sunday.

Palmer was the top overall pick by the Bengals in 2003 and led the franchise to two AFC North titles in eight seasons. Cincinnati granted his trade request to the Raiders in 2011.

Palmer has been a longtime fan of Joe Burrow. Palmers brother, Jordan, worked with Burrow throughout the draft process in 2020 before the Bengals made him the top pick and gave him the same jersey number as Palmers.

"I love everything about him. Hes so level-headed," Palmer said. "You cant stop thinking about that playoff game (against Tennessee) where he got sacked nine times. Its a demoralizing feeling getting sacked that many times. It takes a toll emotionally on you, but you never felt that watching him play. He was cool. He was calm.

"Theres a great belief and energy. And that magic. Hopefully theres enough magic to get past this team of All-Pros and all stars."

Palmer says the biggest key to the game will be for Burrow to get the ball out quickly to be able to beat the Rams pass rush.

"Theyve been so creative with moving (JaMarr) Chase around and finding ways to get him the ball," Palmer said between appearances on Radio Row Wednesday. "Joe (Burrow) just cant sit back there. He has to get the ball out of his hand so that Aaron (Donald) and Von (Miller) cant go to work."

BIG PAYDAY FOR BIG-MAN SCORES

For a guy considered one of the best left tackles in NFL history, Anthony Munoz had excellent hands.

The nine-time All-Pro and first-ballot Hall of Famer had seven catches, including four touchdowns in his career with the Cincinnati Bengals. Munoz would love to see a big man score a touchdown in the Super Bowl because Hydroxycut is giving away $100,000 to a fan if an offensive or defensive lineman finds the end zone. It happened 13 times in the regular season.

"Its good that theyre trying to recognize the big man, so hopefully one of our big men on the Bengals will score a touchdown and somebody can win a lot of money," Munoz said on the AP Pro Football Podcast.

Munoz credits former Bengals coach Sam Wyche for installing plays that called his number as a receiver.

"Playing offense for Sam was so much fun," Munoz said. "You never knew what to expect, but it was great, solid stuff, very innovative."

Three-time Super Bowl champion and two-time Pro Bowl guard Mark Schlereth said he never scored a TD at any level of football in his career. Hes rooting for a jumbo-sized score Sunday.

"I have the joy of scoring as an offense, but never individually scoring," Schlereth said. "As an offensive lineman, you dont get that very often but to have 13 this year, it does happen. A hundred grand would be a nice, little treat."

NEW HEALTH PARTNERSHIP

Hall of Fame Health is partnering with the Off the Field NFL Wives Association to promote health care services for former players and families.

Hall of Fame Heath was launched two years ago during Super Bowl week in Miami to bring world-class health care solutions and services to the football community. Wednesdays announcement increases the focus to wives, children and family members of former players.

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"This may be the most important relationship we will ever form," said Jeremy Hogue, CEO of Hall of Fame Health. "These are strong women, and like most women across the country, they typically make the decisions regarding health care in their homes. They ensure their husbands get the care they need and their kids get the care they need."

The Off the Field NFL Wives Association was founded 16 years ago.

Excerpt from:

Bengals' Zac Taylor optimistic on progress of injured C.J. Uzomah - Fox News

The current farm bill expires in 2023, leading those on Capitol Hill to begin its work of oversight of the 2018 Farm Bill. During hearings in early February, Robert Bonnie, undersecretary for Farm Production and Conservation, as well as Farm Service Agency Administrator Zach Ducheneaux and Natural Resources Conservation Service Chief Terry Crosby each offered their insight into what has worked well and opportunities to improve conservation programs as well as other tenets of the current farm bill.

In his opening statement to Bonnie, House Agriculture Committee Ranking Member Glenn GT Thompson, R-Pa., says in his opinion the committee is a bit behind in our oversight responsibilities and will need to get up to speed on these issues quickly if we are going to complete a farm bill on time next year.

In addition to concerns about funds to target climate practices, Thompson called on Bonnie to help in the discussion on both Title 1 traditional commodity programs and crop insurance as both are under Bonnies FPAC mission area.

Here are five things we heard that piqued our interest in the debate moving forward.

Build Back Better tried to double conservation funding. Thompson criticized the stalled Build Back Better bills attempt to double funding for farm bill conservation programs without any oversight hearings on whether those farm bill conservation programs need changes. Some lawmakers voiced concerns with the Biden administrations laser focus on climate-related ag practices while touting the importance of programs like Conservation Security Program, Environmental Quality Incentive Program, and Conservation Reserve Program for growers. Many bipartisan members of the committee echoed the position held by many of those in agriculture that there are no one-size-fits-all policies when it comes to conservation, so the programs need to allow for local tailoring.

CRP seen as working lands. Although the Conservation Reserve Program has typically been considered an idling lands program, Ducheneaux says he believes changes made to allow for emergency CRP grazing and even baling of those resources allows for producers to stockpile that forage in drought-stricken areas. Hay in the stack is like money in the bank, Ducheneaux says. Stockpiling forage that still considers key primary nesting periods for specific wildlife allows the program to better position itself to offer feed resources when needed and move beyond just idled land.

In the last farm bill, Congress reduced rental rates for CRP and capped acres at 25 million acres for 2021, with incremental increases in that cap to 27 million by FY23. Prior to last year CRP enrollments were down, which led FSA to increase rental rates for its grassland CRP rates by $15 per acre in 1,300 counties and also added a climate-smart practice incentive for CRP general and continuous signups to encourage additional enrollment.

Rep. Dusty Johnson, R-S.D., questioned how these changes are impacting young farmers vying for land. Ducheneaux says CRP does have some limits built into the program to encourage enrollment in the most highly erodible lands. In addition, only 25% of land in a county can qualify for CRP, leaving 75% of potential land available for production. He says there are opportunities to provide transition incentive programs within CRP to help make that transfer of land to the next generation, he says.

Public private crop insurance partnership crucial. Rep. Angie Craig, D-Minn., reiterated that she consistently hears the federal crop insurance program works well and the program does not need changes. Bonnie says maintaining the public private partnership is critically important and remains vital to producers managing risk. Even with the increase in disaster ad hoc assistance in recent years, USDA has linked participation with crop insurance to incentivize producers to utilize those programs.

As we look at the future of crop insurance, weve developed a lot of programs, and well continue to look for ways and gaps in coverage where we can create new products and new opportunities in that partnership, Bonnie says. The last farm bill offered whole farm insurance and micro-farm insurance policies to expand on traditional offerings.

USDA recently rolled out a Post Application Coverage Endorsement PACE in certain states for corn farmers who split apply nitrogen. Bonnie says this is one of many ways the public private partnership is coming together to create new products that create incentives that in this case also offer environmental and economic benefits.

Climate-smart pilot projects offer crucial insight. USDA announced $1 billion in Commodity Credit Corporation funds to offer grants to pilot projects of varying sizes to work directly with producers and the private sector on establishing climate-smart commodities. Bonnie says this area is ripe for improvement in building on funding offered through the Regional Conservation Partnership Program to partner together private dollars with taxpayer dollars.

Bonnie says with this pilot program USDA hopes to provide learning and create a conversation on incentives, measurement and verification of climate-smart practices that eventually will provide new revenue streams for farmers. Despite questions on whether CCC funds can be directed by USDA without Congressional direction, Bonnie defended the action because it supports ag markets similar to the way CCC funds were used during the pandemic and trade war.

Staffing levels still low at USDA. Many members questioned the USDA officials about staff on the ground that interface with producers. Bonnie was quick to note, We need more people at NRCS and FSA, he says.

Cosby says NRCS has an aggressive hiring strategy and has been able to hire 3,000 employees in the last two years. Theyre working closely with state conservationists to fill the remaining 700 needed staff positions. Bonnie adds when looking towards the next farm bill, NRCS will need more boots on the ground to provide sound technical insight as well as outreach to small, medium and historically-underserved farmers.

No need to create a climate title. Committee Republicans emphasized that the conservation title must not be repurposed as a climate title when the farm bill is reauthorized in 2023, and the many practices and actions encouraged in other farm bill titles that improve overall farm sustainability cannot be forgotten. House Agriculture Committee Conservation and Forestry Subcommittee Chairman, Abigail Spanberger, D-Va., vowed the title would remain the conservation title, although she praised the ability for Congress to focus dollars that offer climate-smart benefits and ensure farmers stay on the land through economic sustainability within that title.

Read more:

Farm bill oversight begins - Farm Progress

The Williamstown Theatre Festival has released a progress report on its ongoing efforts to respond to allegations of racism, dangerous working conditions, equity shortcomings, and more. The claims were raised by an alumni group featured in a Los Angeles Times expos in September. The following month, then-artistic director Mandy Greenfield abruptly resigned and Jenny Gersten, who served as artistic director from 2010-2014, returned in an interim capacity. WAMC spoke with Gersten about what WTF has identified in its new report, as well as her reaction to continuing criticism from the alumni group whose letter to leadership sparked the reckoning.

GERSTEN: The report that we released last week is the result of, I would say, two years of conversations that have been happening at the Williamstown Theatre Festival. So as much as it's true it is in part in response to some of the more recent, you know, information that's come to light or certain allegations that were brought up. it was really part of a full staff effort to sort of respond to the times because they're, you know, they're changing.

WAMC: So let's dial in some of the specifics. What initiatives are underway that the report identifies?

Well, one of the things we did back in 2021, was that we changed the structure of what was formerly our apprentice program into a learning program. Last year was specifically in partnership with Black Theatre United, a company that started during 2020 in response to some of the racial reckoning, Black Lives Matter movement that was going on in a big way that year. Black Theatre United partnered with Williamstown Theatre Festival to create a BIPOC theatre makers program for 10 learners in residence at the festival. And it combined some pedagogy or academic learning, some experiential learning, mentorship with members of Black Theatre United, and other meaningful ways of engagement at the theatre festival. So, when we once had, you know, people applying to become apprentices at the festival, we're now interested in changing it so that it has more of an educational component and more of a structure with limitations to how many hours they're spent doing any labor at the festival.

One theme in the criticism lodged at the festival concerned a culture where employees felt that it was either uncomfortable or unclear on who they could report concerns about labor conditions or equity issues to within the organization. Has the report addressed those concerns?

Yeah, in several ways. I mean, one of the things we did was we have just hired a woman named Danielle King, who is going to be the producer of shows and of organizational culture, really thinking about people and culture at the senior level of the organization, so that there is someone on staff. We also started working with a third-party HR firm back in 2021. So we had a full time consultant in HR working with us, as well as someone BIPOC available to BIPOC members of the festival, if there were HR-type issues that we needed, that needed to be addressed, but more personally. And I'm just trying to think of- A lot of the reporting structure, just in terms of anonymous reporting, those, the report also makes room for ways to make it available without, with- And keep anonymity.

Back in November, when WAMC reported on your return to the festival when Mandy Greenfield departed, the WTF, Williamstown?! Collective, the group of alumni who wrote the much publicized letter to the festival concerning a lot of these criticisms, offered a statement back to us citing their concern that I'm going to quote here the only public and concrete step at the festival was made is to rehire a former artistic director who presided over the same toxic institutional practices. When you hear a sentiment like that, where there's concern that you were attached to the festival at what they have described as the height of many of these concerns- Do you have a response to that?

I mean, I think- I understand where they're coming from. You know, I think our awareness of how, of that kind of toxicity, at least for me, personally, has really evolved over time. So I think, the way I thought about the culture back then when I worked at the theatre festival versus how I understand it now, and partly because of the WTF Collectives ability to sort of raise these concerns, and partly because our whole industry is changing. And the generations of young people today who are standing up for what they think is fair and correct behavior by an employer are just- They've shifted, and I think it's important to be responsive to them and understand where they're coming from. So I think that's what we're doing now. It's, you know, it's hard to hear it, Josh, but it's, on the other hand, we all need to change.

Looking back at your first tenure at the festival, do you have any regrets about how you conducted yourself as its leader?

[pause]

I don't. I actually, I'm really proud of my time at Williamstown, in both eras that I worked there. I mean, I understand where you're coming from with that, but, uh- But that's not how I, thats not how I look back on it.

Looking forward, what comes next from the report? When are we going to see more action taken by the festival?

Well, again, I think we're just at- The reason that we're releasing this as a progress report as opposed to sort of a document of, that sort of finite, is we're saying, this is an organic process, we're going to keep learning as we make these changes, and implement these new ideas and put them into practice. We're going to see where the pinch points are when we try these new efforts and work together to address the new potential complications that arise out of it. But I think we intend to release a progress report at least once a year, as well as making small amendments throughout the time that it lives on our website so that we can be held continue to be held accountable. So that it has, that we're constantly being responsive to what we learn.

Jenny, are there any questions about the report I haven't thought to ask you that you think it's important for folks to understand?

Its a great question. I think the question, Josh, is, maybe, how does this change the Williamstown Theatre Festival that I know and love, because I'm reading a lot about anti-oppression and anti-racism, but there probably are some listeners out there who think, you know, I loved my Williamstown Theatre Festival the way it was, and I never understood that these were real problems because I, you know, I love the shows and it's important to me that the theatre festival continue to exist and thrive in the Berkshires. And so I think that's going to all happen too. I don't think this report changes what we do culturally, to contribute to the life of the arts in the Berkshires. It just makes us more responsible humans.

Link:

Williamstown Theatre Festival issues a progress report on efforts to address allegations of racism, poor labor conditions - WAMC

Dear School District of Philadelphia Families,

The School District of Philadelphia is excited to announce that on Thursday, February 10th, 2022, we will release the school year 2020-2021 School Progress Report on Education and Equity (SPREE).

The new SPREE replaces the old School Progress Report (SPR) which provided information about each schools achievement and areas for improvement. The SPREE is an enhanced tool that aligns more closely with the Board of Educations Goals & Guardrails, which set clear expectations for what students must be able to accomplish and the conditions that must be in place at each school to empower our students to succeed in and beyond the classroom. The SPREE highlights our overall progress as a District and shows each schools growth in both traditional performance measures like proficiency on state assessments and graduation rates, as well as additional measures of school climate, culture and opportunity.

As we know all too well, 2020-2021 was not a normal school year. Because the pandemic forced us to shift to virtual learning, many students did not take state assessments like Keystones and PSSAs. Therefore, because that assessment data informs various SPREE measures, the report for the 2020-21 school year, which will be called SPREE Lite, will look slightly different than future reports. It will not include performance information in the areas of Reading & English Language Arts or Math & Science, nor will it include overall scores. Instead, each schools SPREE Lite will show the list of all the metrics that will be scored in future SPREE reports, but will only provide performance information for the measures that we could assess at this time College & Career Readiness and Climate, Culture & Opportunity.

We have developed a few helpful resources to assist you in reading and understanding the SPREE. This Family Guide provides an overview of the SPREE and how it connects to the Goals & Guardrails. This User Guide provides more detailed and technical information about how we calculate scores for each measure. And finally this FAQ will answer additional questions that you may have. All of these resources and more can be found on the SPREE website at http://www.philasd.org/spree.

Thank you for partnering with the District as we strive together to help all students succeed!

Last modified: February 8, 2022

Excerpt from:

District to Release 2020-2021 School Progress Report on Education and Equity (SPREE) The School District of Philadelphia - philasd.org

With 9 approved markers in nonsmall cell lung cancer and a plethora of established and emerging therapies that have been designed to target them, the need for molecular testing is more important than ever.

With 9 approved markers in nonsmall cell lung cancer (NSCLC) and a plethora of established and emerging therapies that have been designed to target them, the need for molecular testing is more important than ever, according to Joel W. Neal, MD, PhD, who added that this group is projected to expand even further, with the emergence of targets such as HER2 exon 20 insertions and amplification, MET amplification, and NRG1 fusions.

It is really [imperative] to do the testing; [we need] to find all these targetable molecular alterations. Tumor testing is the gold standard. However, I believe RNA tissue testing is going to be [an emerging] gold standardespecially for patients in whom we didnt find [a driver alteration] by liquid biopsy or tumor tissue biopsy, Neal said in a presentation delivered during the 19th Annual Winter Lung Cancer Conference, an event hosted by Physicians Education Resource, LLC.1 The problem is, with next-generation sequencing and DNA testing of tissue, [the process] can be really slow. Liquid biopsies are fast and convenient. But [well] keep looking until we find it. The rest of my talk is irrelevant if you miss the target in the patient.

In his presentation, Neal, an associate professor of medicine/oncology at Stanford University, detailed the many advancements made in the treatment of patients with NSCLC whose tumors harbor ALK mutations, ROS1 rearrangements, MET exon 14 alterations, RET fusions, and NTRK fusions, as well as emerging information on newer targets that have come to light.

The preferred options for utilization in the first-line setting in ALK-positive lung cancer are brigatinib (Alunbrig) and alectinib (Alecensa), according to Neal. That is because these drugs, along with lorlatinib [Lorbrena], have all cleanly been shown to be superior to crizotinib [Xalkori], the first drug that was FDA approved for [this disease], Neal said.

In December 2015, the FDA granted an accelerated approval to alectinib for the treatment of patients with ALK-positive disease following progression on or were intolerant of crizotinib, based on data from 2 single-arm phase 2 clinical trials (NCT01871805; NCT01801111), which showed objective response rates (ORRs) ranging from 38% to 48%.2-3 Approximately 2 years later, in November 2017, they agent received a regular approval based on findings from the phase 3 ALEX trial (NCT02075840), after it was found to result in improved progression-free survival (PFS) vs crizotinib.4

Among 303 patients with ALK-positive disease who did not previously receive systemic therapy for metastatic disease, the median PFS with alectinib (n = 152) was 25.7 months (95% CI, 19.9not estimable) per independent review committee (BIRC) assessment vs 10.4 months (95% CI, 7.7-14.6) with crizotinib (n = 151; HR, 0.53; 95% CI, 0.38-0.73; P < .0001).

In April 2017, the FDA granted an accelerated approval to brigatinib for use in patients with ALK-positive NSCLC whose disease was resistant to prior crizotinib.5 This decision was based on data from the phase 2 ALTA trial (NCT02737501). Final data from the trial, presented during the 2021 ESMO Congress, showed that at a median follow-up of 40.4 months (range, 0-52.4) with brigatinib (n = 137) and 15.2 months (range, 0.1-5.7) with crizotinib (n = 138), the median BIRC-assessed PFS was 24.0 months (95% CI, 18.5-43.2) and 11.1 months (95% CI, 9.1-13.0), respectively (HR, 0.48; 95% CI, 0.35-0.66; P < .0001).6

In November 2018, lorlatinib garnered an accelerated approval for the treatment of patients with metastatic ALK-positive NSCLC who progressed on 1 or more ALK TKIs.7 The indication was expanded in March 2021, for use in the frontline setting based on data from the phase 3 CROWN trial (NCT03052608), in which lorlatinib resulted in a 72% reduction in the risk of disease progression or death vs crizotinib in 296 treatment-nave patients (HR, 0.28; 95% CI, 0.19-0.41; P < .0001) per BICR assessment.8

Why are [these options] superior [to crizotinib]? Well, alectinib, brigatinib, and lorlatinib all [have shown the ability to] overcome many of the acquired resistance mutations, which are much more complicated than the relatively simple T790M that we used to see in EGFR-mutant lung cancer, Neal explained. In addition, most of the newer second- and third-generation ALK inhibitors have much better central nervous system [CNS] penetration, and [this population] has a high risk of brain metastases. As such, its clear that crizotinib is no longer the standard of care.

Tumors that have become resistant to any of these drugs can be re-biopsied to identify secondary mutations. Only approximately 30% of those who have these tumors have secondary mutations that are targetable, according to Neal. If we try second- or third-generation ALK inhibitors and they become ineffective, chemotherapy is the standard, Neal said. I do not recommend immunotherapy with that. I favor bevacizumab [Avastin]-based [treatment] or just platinum chemotherapy.

In March 2016, crizotinib was approved by the FDA for use in patients with advanced NSCLC whose tumors harbor a ROS1 gene alteration, based on findings from the phase 1 PROFILE 1001 trial (NCT00585195).9 Data from an expansion cohort of the phase 1 trial showed that among 50 patients who received the agent at the standard twice-daily dose of 250 mg, crizotinib elicited an ORR of 72% (95% CI, 58%-84%) with a median duration of response (DOR) of 17.6 months (95% CI, 14.5not reached [NR]) and a median PFS of 19.2 months (95% CI, 14.4-NR).10

Additional findings from the EUROS1 cohort of a retrospective study showed that among 32 patients, 29 of whom evaluable for best response, the ORR achieved with crizotinib was 80%, the disease control rate was 86.7%, and the median PFS was 9.1 months.11

It was just a stroke of luck that crizotinib happened to inhibit ROS1 gene rearrangements. It was originally designed was a MET inhibitor, and thats what the phase 1 trial was, Neal noted. Theres a lot of evidence for crizotinib, which is an FDA-approved therapy based on data from phase 1 extensions of clinical trials and phase 2 expansion cohorts.

Entrectinib (Rozlytrek) joined the US treatment arsenal for this population in August 2019 after the agent was shown to elicit an ORR of 78% in 51 adult patients examined across several clinical studies.12 Of the 40 patients who were noted to have experienced tumor shrinkage, 55% had shrinkage that persisted for at least 1 year.

Additional data from 32 patients with ROS1 inhibitornave NSCLC who were enrolled across phase 1 and 2 trials examining the agent at a once-daily dose of 600 mg given in 4-week cycles showed that the BICR-assessed ORR was 69%, the median DOR was 28.6 months (95% CI, 6.8-34.8), and the median PFS was 29.6 months (95% CI, 7.7-36.6).13

Entrectinib has a slightly different toxicity profile than crizotinib, which tends to be pretty well tolerated with some mild gastrointestinal [GI] effects and lower extremity edema. Entrectinib is also fairly well tolerated, with a bit more dysgeusia, fatigue, some dizziness, weight increases, and paresthesia, Neal noted. However, the biggest distinguishing factor between the 2 options is the CNS penetration. Its clear that entrectinib can get into the CNS, whereas crizotinib does not have effective CNS penetration.

Integrated data from three phase 1/2 trialsALKA-372-001 (EudraCT 2012-000148-88), STARTRK-1 (NCT02097810), and STARTRK-2 (NCT02568267)showed that at a median follow-up of 15.5 months, within the cohort of patients with ROS1-positive NSCLC who had measurable CNS disease (n = 12/53), the intracranial ORR achieved with entrectinib was 75.0% (95% CI, 42.8%-94.5%).14 The median intracranial DOR was 12.9 months (95% CI, 4.6not evaluable [NE]), and the median intracranial PFS was 19.3 months (95% CI, 3.8-19.3).

With crizotinib, usually we would see CNS response rates ranging from 20% to 30% and they are not durable, Neal said. Entrectinib is clearly the preferred agent for patients with newly diagnosed ROS1-positive NSCLC and brain metastases. Otherwise, its a toss-up right now.

After disease progression on crizotinib or entrectinib, agents like lorlatinib and repotrectinib may represent potentially effective options. Data from a phase 2 trial (NCT01970865) showed that among 34 patients who had received prior crizotinib, lorlatinib elicited an ORR of 27%, a median DOR that had not yet been reached, and a median PFS of 8.5 months.15 Additionally, preliminary findings from the phase 1/2 TRIDENT-1 trial (NCT03093116) showed that among 18 patients with ROS1-positive NSCLC who were TKI pretreated, repotrectinib elicited a confirmed ORR of 39% (95% CI, 17%-64%).16

After crizotinib or entrectinib, lorlatinib is not on label, but it is an agent to consider and see if it works, Neal said. Then theres repotrectinib, not yet FDA approved, but has promising data both for systemic response rates after crizotinib and some CNS intracranial penetration. Repotrectinib is an exciting new therapy that we can keep our eyes on.

Crizotinib has known activity in patients with MET exon 14 (METex14) skipping mutations, according to Neal. Data from an expansion cohort of the phase 1 PROFILE 1001 (NCT00585195) showed that among 52 evaluable patients who harbored this mutation and received a twice-daily dose of 250 mg, the ORR was 32%, the median DOR was 9.1 months, and the median PFS was 7.3 months.17

However, 2 new agents have since garnered regulatory approval from the FDA for use in this patient population: tepotinib (Tepmetko) and capmatinib (Tabrecta).18,19 Findings from the phase 2 VISION trial (NCT02864992) indicated that 157 patients with METex14-altered disease, the ORR with tepotinib was 44.7% (95% CI, 36.7%-53.0%), the median DOR was 11.1 months (95% CI, 8.4-18.5), and the median PFS was 8.9 months (95% CI, 8.2-11.2).20

Data from the phase 2 GEOMETRY mono-1 trial (NCT02414139) showed that capmatinib induced an ORR of 68% (95% CI, 48%-84%) by independent review in 28 treatment-nave patients with METex14-altered disease.21 Among those who received 1 or 2 prior lines of therapy (n = 69), the ORR with capmatinib was 41% (95% CI, 29%-53%).

They look similarly effective overall, with similar safety profiles. Both have better CNS penetration than crizotinib, and they look like they have a longer DOR overall, Neal said. I would go with tepotinib or capmatinib before I would consider crizotinib [in these patients].

Other MET inhibitors, like glesatinib (MGCD265), savolitinib, and elzovantinib (TPX-0022) are currently under development, along with MET bispecific antibodies and antibody-drug conjugates.

Off label, we used to use a lot of drugs to treat those with RET gene rearrangements that were identified, but most of these drugs had a lot of VEGF activity, a lot of toxicity, Neal explained. Vandetanib [Caprelsa], cabozantinib [Cabometyx], even alectinib, were fairly toxic and not particularly well tolerated. As such, it was super exciting when a couple of new agents came out.

In May 2020, the FDA granted an accelerated approval to selpercatinib (LOXO-292; Retevmo) for use in patients with RET-positive NSCLC based on findings from the NSCLC cohort of the phase 1/2 LIBRETTO-001 trial (NCT03157128).22 Among 105 patients who were previously treated with platinum chemotherapy, the ORR with the agent was 64% (95% CI, 54%-73%). Earlier data revealed that selpercatinib also elicited a CNS ORR of 91% (95% CI, 59%-100%); at a median follow-up of 9.6 months, the median PFS with the agent was 18.4 months (95% CI, 12.9-24.9).23 Were looking at an 18-month PFS, which is like what we see for EGFR and osimertinib [Tagrisso]this is great, Neal underscored. Regarding [adverse] effects, there is peripheral edema, headaches, and some VEGF-associated toxicities, but they are generally manageable.

Later that year, in September 2020, the FDA gave the green light to pralsetinib (Gavreto) for use in adult patients with RET fusionpositive NSCLC based on findings from the phase 1/2 ARROW trial (NCT03037385).24 At a data cutoff of May 22, 2020, the ORR was 61% (95% CI, 50%-71%) among 87 patients who previously received platinum-based chemotherapy; the ORR was 70% (95% CI, 50%-86%) among 27 treatment-nave patients.25 Data from a post-hoc analysis of the trial indicated that the ORR was 51% (95% CI, 34%-68%) in those with a history of CNS involvement and prior platinum-based treatment.

Pralsetinibhas similarly high efficacy and response rates in virtually all patients who receive it. [We also see] shrinkage of brain metastases. Both agents appear to be effective in the CNS, Neal said. As such, I would recommend selpercatinib or pralsetinib for the first-line treatment of these patients, as well as the consideration of chemotherapy and probably immunotherapy in the next-line setting.

NTRK was identified across many tumor types, including about 0.1% of NSCLCs. I think we have had 2 patients, ever, at Stanford who have been diagnosed with it, Neal explained. It is very, very rare in lung cancer, but there are a couple of FDA-approved therapies [for those whose tumors harbor it].

In November 2018, larotrectinib (Vitrakvi) was granted an accelerated approval from the FDA for use in adult and pediatric patients with select solid tumors that have a NTRK gene fusion.25 Data from an analysis that incorporated findings from 12 patients with NSCLC who were enrolled to 2 clinical trials (NCT02122913; NCT02576431) showed that at a median follow-up of 12.8 months, larotrectinib (Vitrakvi) elicited an ORR of 75%, and the median DOR had not yet been reached (range, 3.9+ to 25.9+).26

Larotrectinib works in almost all patients with lung cancer, as well as other NTRK-positive tumors, Neal noted. It comes with adverse effects, like edema and pyrexia.

Entrectinib has also been indicated for use in the treatment of adult and pediatric patients aged 12 years or older with solid tumors that harbor an NTRK fusion.12 The indication is specific to those who have a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity and have progressed on therapy or have no alternative treatments.

Integrated data from ALKA-372-001, STARTRK-1, and STARTRK-2 showed that among 10 patients with NTRK-positive NSCLC, the ORR with entrectinib was 70.0% (95% CI, 34.75%-93.33%), the median DOR was not yet evaluable (95% CI, 10.4-NE), and the median PFS was 14.9 months (95% CI, 4.7-NE). Notably, the BICR-assessed intracranial response achieved with the agent was 66.7%.14

Additionally, LOXO-195 (BAY 2731954) is a selective TRK inhibitor that is currently under exploration in a phase 1 study (NCT03215511), where it has already demonstrated preliminary efficacy in those with resistance to prior TRK inhibitors mediated by TRK kinase mutations.27 Among 20 patients with a TRK kinase mutation, the ORR with the agent was 45%.

If you have a patient with a NTRK-positive tumor, I recommend a clinical trial after progression through standard therapy and regular chemotherapy. Do not miss [this target], but I do think you will find it doing RNA or DNA sequencing, when you are looking for everything else.

NRG1 rearrangements contain EGF-like binding domain of NRG1, or the ERBB3 ligand. The rearrangement is relatively uncommon, according to Neal, who added that the frequency is uncertain but likely occurs in less than 1% of those with NSCLC, and in never smokers.

They can probably best be detected by RNA-based testing, Neal added. Afatinib has a little bit of response, 25%, but Im not sure that I would recommend it off label yet.

The fully human anti-HER3 monoclonal antibody seribantumab is under exploration in patients with solid tumors harboring an NRG1 fusion as part of the phase 2 CRESTONE trial (NCT04383210). Tarloxotinib bromide, an irreversible EGFR/HER2 inhibitor is under investigation in patients with NSCLC harboring EGFR exon 20 insertion and HER2-activating mutations, as well as other solid tumors with NRG1/ERBB gene fusions, as part of the phase 2 RAIN-701 trial (NCT03805841). Lastly, the HER2/HER3 bispecific antibody zanocutuzumab (MCLA-128) is being evaluated in patients with solid tumors harboring an NRG1 fusion as part of a phase 1/2 trial (NCT02912949).

I am excited that some other agents [are under exploration, as well], Neal concluded. Lets just say anti-HER3 inhibition looks like a possible way to target these [fusions].

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Efforts to Effectively Target Rare Oncogenes Propel Progress in Lung Cancer - OncLive

SUNNYVALE, CAAttacking the ignorant Luddites who questioned the wisdom and necessity of the program, the nations top tech leaders issued a statement Thursday calling their industrys plan to create an army of AI-controlled bulletproof grizzly bears an unavoidable and inevitable part of progress. Lets be real: Sentient machines that control thousand-pound bears with razor-sharp titanium claws are going to happen no matter what we do, so we might as well be the ones who do it, said Meta CEO Mark Zuckerberg, who, along with leaders such as Alphabets Sundar Pichai and Amazons Jeff Bezos, signed a letter pushing back against critics who had described the Grizzly Project as dangerous, unnecessary, and damaging to humanity. Any kind of regulation on this front will only hinder Americas ability to design and mass-produce high-quality indestructible grizzlies, which is the way the world is headed. You cant stop progress, and you cant really separate deadly bears that shoot acid from their mouths from the technology that helps people every day. Besides, these grizzlies have many nonlethal uses. Do you want to deny an elderly woman a powerful machine-bear hybrid that can carry her groceries and dispense her medication just because it also has the potential to kill millions of human beings? At press time, Congress had approved $8 billion in research grants for the Grizzly Project after hearing China was well on its way to developing fire-breathing pandas.

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Tech Leaders Justify Project To Create Army Of AI-Controlled Bulletproof Grizzly Bears As Inevitable Part Of P - The Onion

Theres an exercise I do in my law firm diversity, equity, and inclusion (DEI) trainings. I call it the Ten-Year Challenge. I show a slide with race, ethnicity, and gender stats for large law firms 10 years ago. Then I show stats from this year. Then I ask my group, What has changed?

The answer? Not much.

To quote Bloombergs law firm DEI report from November 2021:Nine out of 10 top leaders (either CEO or managing partner) are White and 81% of top leaders are male. Of attorneys who lead firm-wide practice groups or departments, 27% are White women, 6% are minority men, 4% are minority women, and the remainder are White men.

We arent moving backwards. But we arent moving forward as quickly as we could be. At Inclusion Nation, weve worked with many law firms on DEI. Here are five of the biggest reasons I see for our slow progress on racial and ethnic diversity in large law firms.

If the business case for diversity were the magical understanding that firm leaders needed, we would have solved DEI a generation ago. It is not.

People are not widgets. Putting a return value on investment in a human life is not how we start. Not every client is pushing for a diverse team, and not every matter implicates the transforming population of the workplace. Your case for diversity doesnt need to have an extensive historical backing or be based solely on realizations from the global racial reckoning of summer 2020.

It can be as simple as this: Prioritize the success of people who work in your law firm because you hired them, and they should have an equal chance to succeed.

Yes, we should look outside of ourselves for solutions, but we should also remember that our profession is unique. Law firms can be hierarchical and traditionalist. Practice groups, and even partners, are often silos within firms.

Lawyers have never been taught how to manage peopleever. Attrition rather than retention can be beneficial to profits-per-partner. And Big Law has a large proportion of employeesincluding many women and people of colorwho are often not considered in most firms diversity work because they dont have JDs.

Your diversity consultant or in-house professional doesnt have to have a legal background, but they should have some grounding in law-firm life to recognize what can workand what will never workin Big Law.

The best law firms delivering DEI success are ones that allow their DEI professionals the runway to succeed. Those firms do not limit which attorneys the DEI professionals can work with, or second-guess the professionals approaches because they dont fit the culture of the firm.

They succeed at balancing a hands-off approach (you figure it out!) and a micromanager approach (heres what 16 different partners believe you should do) and choose not to take the slippery slope approach to DEIif we do this, then all these terrible actions will inevitably result.

I should also mention that many Big Law DEI professionals are women, and women of color, and the biases and stereotypes I discuss in my trainings apply there as well. If you are already biased to believe someone is not competent because of the identity they have, then you are already inclined to underestimate and undervalue them.

If youre hiring someone to do an extraordinarily difficult job, give the person you chose the resources, the confidence, and the time to succeed.

One of our most popular workshops at Inclusion Nation is where stakeholders work together to identify the root cause of specific DEI challenges, then design a testable four-part solution to address it. You know what they often find? Many of the solutions are programs already in place that can be adjusted to fit diversity needs.

What do you already do for talent acquisition? Succession-planning? Business generation? We call it using a DEI lens. You partner with law schools for on-interviews. How can you do that with a DEI lens? You made accommodations for remote workers. How can you do that with a DEI lens? You coach high performers. How can you do that with a DEI lens?

You already have existing talent development initiatives. Re-design them with a DEI lens.

Imagine you are a person of color. None of the partners you work with are of the same race or ethnicity as you.

None of them went to the same schools as you. Some of them were in sororities and fraternities, but they have never heard of yours.

None of them grew up in neighborhoods like yours. You like different music, fashion, movies, TV shows, and sports. You celebrate different holidays. You have different family structures. You have different opinions on social justice.

And there are comments you hearwhere are you really from, youre so well-spoken, what interesting hair, your names hard to pronouncewhat we politely call microaggressions. You look at the culture of a firm that says its inclusive and feel like inclusive does not include you. It. Is. Exhausting.

The best law firms are ones that know that new hires, at whatever level they enter the firm, will feel that exhaustion. Those firms ensure through onboarding, employee resource groups, thoughtful mentoring matches, personal development plans, and invested executive committee members, that both attorneys and business professionals can feel like they can belong here. That is the real work of change.

This article does not necessarily reflect the opinion of The Bureau of National Affairs, Inc., the publisher of Bloomberg Law and Bloomberg Tax, or its owners.

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Michelle Silverthorn is a licensed attorney, founder, and CEO of Inclusion Nation. She practiced for large law firms in New York and Chicago before transitioning to the diversity field, where she has trained thousands of lawyers about bias, race, equity, and belonging in the workplace. She is author of the book: Authentic Diversity: How to Change the Workplace for Good.

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Law Firm Diversity: Five Reasons for Slow Progress - Bloomberg Law

Can global businesses meet ethical standards for behavior even as theyre struggling to survive?

The initials ESG for environmental, social and governance present supply chains with a huge responsibility. They must simultaneously ensure the humane treatment of workers throughout the supply chain, make progress toward the goal of net-zero emissions, and generally practice good corporate governance. Oh, and by the way they need to make a profit. Which is becoming increasingly difficult in these days of pandemic, congested supply lines, rising inflation and uncertain demand. On this episode we discuss balancing all of these priorities with John Ferguson, practice lead for globalization, trade and finance with Economist Impact, a new arm of The Economist Group that aims to achieve progress on major global issues. We discuss whether companies commitment to ESG extends beyond good intentions, and the obstacles that stand in the way of doing good while doing well. Hosted by Bob Bowman, Editor-in-Chief of SupplyChainBrain.

Show notes:

An Economist Impact report on Sizing the Energy Transition.

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Podcast | The ABCs of ESG: Are Supply Chains Making Progress? - SupplyChainBrain

The ban on surprise billing in health insurance programsincluding the federal employee/retiree FEHB programthat took effect at the start of this year is not an absolute one and its implementation is still a work in progress, according to the Kaiser Family Foundation.

The foundation, which produces reports and recommendations on health insurance issuesand which is not associated with the Kaiser health-care providersaid the change in law creates important new protections against being hit with unexpected charges for unknowingly getting care from providers outside of their plans network.

Such billing can occur, for example, in emergency and other urgent care settings when enrollees dont have time to check whether facilities are in-network, or when they receive care at an in-network facility from providers who are out of network. The foundation had found in a 2019 survey 39 percent of respondents had received an unexpected medical bill in the prior 12 months, 13 percent of those for $2,000 or more.

The 2020 No Surprises Act, passed with bipartisan support, bans surprise billing for emergency services, bans high out-of-network cost-sharing for emergency and non-emergency services, bans out-of-network charges for ancillary care (such as for anesthesiologist or assistant surgeon) at an in-network facility, and bans other out-of-network charges without advance notice.

The law is highly complex, however, setting coverage and billing standards for a specific subset of private insurance claims that could number 10 million annually. Providers are permitted to ask consumers to waive their NSA protections in some cases, the analysis said.

While audits of health carriers will provide some oversight of their compliance, that will involve various federal and state entities and it remains to be seen how these new systems will work, independently and in coordination.

To a large extent, oversight and enforcement will rely on complaints. In order to complain, though, consumers will need to understand that they should not be overbilled for emergency services or for non-emergency out-of-network services while they are in in-network hospitals and facilities, it said.

Finally, it remains to be seen if any other tools will be employed to monitor trends in the incidence of surprise medical bills, and how effectively the law may work to protect consumers from surprise bills and reduce their out-of-pocket costs, it said.

Annual Leave, One of Top Benefits to Federal Employees

Benefits Upon Passing of a Federal Employee or Retiree

Retirement Income Myths

Guidance Issued on Marijuana and Federal Employee Security Clearances

The Federal Retirement Deal (Its a Very Good One!)

TSP Outlines Strings Attached to Upcoming Investment Window

Leaving Federal Service? Go Out With Class

When Should a Federal Employee Apply for Social Security Benefits?

Federal Retirement Mistakes to Avoid

Federal Retirement: When Age Isnt Just a Number

FERS & CSRS: What Happens to Your Annuity if You Come Back?

2022 GS Locality Pay Tables here

FERS Retirement Guide 2022

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Ban on Surprise Billing in Health Plans a Work in Progress, Analysis Says - FEDweek