'Radionuclide-Containing Combo Slows Metastatic Prostate Cancer, Improves Survival'

 Men with castration-resistant prostate cancer (CRPC) and asymptomatic or mildly symptomatic bone metastases lived significantly longer when they received enzalutamide (Xtandi) plus radium-223 (Ra-223, Xofigo), a large randomized trial showed.

Median radiographic progression-free survival (rPFS), the primary endpoint, improved from 16.4 months with enzalutamide along with 19.4 months with the addition of Ra-223. Median overall survival (OS) improved from 35.0 to 42.3 months with combination therapy.

The improved survival came with increased toxicity, as grade ≥3 drug-related adverse events (DRAEs) increased from 19% to 28%, but relatively few patients discontinued because of DRAEs, reported Silke Gillessen, MD, of the Oncology Institute of Southern Switzerland in Bellinzona, at the European Society for Medical Oncology (ESMO)opens in a new tab or window congress in Barcelona.

"These results support the combination of enzalutamide plus radium-223 plus a bone protecting agent as a potential new first-line mCRPC option for patients with prostate cancer and bone metastases who have not received a prior androgen receptor-pathway inhibitor," she concluded.

The PEACE-3opens in a new tab or window trial results are practice changing, with caveats about the need for long-term OS data and missing data on osteonecrosis of the jaw, said ESMO invited discussant Karim Fizazi, MD, of the Gustave Roussy Institute in Villejuif, France.

"Combining enzalutamide and radium clearly improves the primary endpoint of the trial and most likely also overall survival," said Fizazi. "If you're using this combination in your practice, please make sure you prescribe a bone-protecting agent. [Bone] symptoms are no longer needed. If you're using radium-223 historically, this was a need in the first pivotal phase III trial, but this was not the case here, so we can actually probably treat patients without bone pain." Previous studies were limited to patients with symptomatic bone disease. PEACE-3 enrolled patients with no or minimal symptoms.

"Also, if you're using enzalutamide in your practice, make sure you measure blood pressure. This is needed, and please treat hypertension," Fizazi stated.

"More data are needed in PEACE-3, but this is really the first look at the data," Fizazi said. "As more trials with radium-223 phase III trials are maturing, we need to optimize the best use for radium-223 versus lutetium, which is also a standard of care, and hopefully soon, other radiopharmaceuticals for prostate cancer patients."

Both abiraterone (Zytiga) and enzalutamide are standard first-line options for mCRPC that has progressed on androgen deprivation therapy (ADT), Gillessen noted. No combination had improved rPFS and OS in the first-line setting. In fact, a randomized trialopens in a new tab or window of abiraterone plus Ra-223 led to worse OS and an increased fracture risk in men with asymptomatic mCRPC as compared with the androgen receptor pathway inhibitor alone.

In the era prior to introduction of androgen receptor pathway inhibitors, Ra-223 improved OS in the phase III ALSYMPCAopens in a new tab or window trial.

Continuing investigation of combination therapy, the PEACE-3 trial enrolled patients with mCRPC and bone metastases, asymptomatic or mildly symptomatic, no prior treatment with enzalutamide or Ra-223, and ongoing ADT. Patients were randomized to receive single-agent enzalutamide or in combination with Ra-223. The primary endpoint was rPFS, and key secondary endpoints included safety, OS, time to next treatment, time to pain progression, and time to first symptomatic skeletal event (SSE).

Use of a bone-protecting agent was mandated after enrollment of the first 119 patients. The trial had an accrual goal of 560 patients, but closed with 446 patients because of slow accrual. Baseline characteristics were well balanced.

The primary analysis showed that the addition of Ra-223 was associated with a 31% reduction in the rPFS hazard ratio (95% CI 0.54-0.87, P=0.0009). A subgroup analysis showed a consistent benefit for the addition of Ra-223. An interim analysis of OS also showed that the combination therapy was associated with a 31% reduction in the hazard ratio (95% CI 0.52-0.90.) The hazard was associated with a P-value of 0.0031, which met the prespecified level for statistical significance of P<0.0034.

The time to next systemic treatment was significantly prolonged in the combination arm. After 24 months, 51% of patients randomized to single-agent enzalutamide had initiated a next systemic treatment as compared with 30% of patients in the combination arm (HR 0.57, 95% CI 0.44-0.75, P<0.0001).

Time to pain progression at 24 months (45% with enzalutamide, 48% with the combination) did not differ significantly between the two groups nor did time to SSE (18% in each arm).

DRAEs (84% vs 71%), serious AEs (43% vs 30%), and serious DRAEs (8% vs 1%) all occurred more often in the combination arm. Grade 3-5 DRAEs occurred in 28% of patients randomized to Ra-223 versus 19% of those who received single-agent enzalutamide. Fatal AEs occurred in 3% of the combination arm and 2% of the enzalutamide arm. Treatment discontinuation related to enzalutamide toxicity was 8% and 7% in the two arms, and 3% of patients in the combination arm discontinued because of Ra-223-associated toxicity.

The most common treatment-emergent AE was hypertension, which occurred in a third of patients in each arm. Treatment-related hypertension occurred in 12% of patients in each group.

Disclosures

The PEACE-3 trial was supported by Astellas Pharma and Bayer Healthcare Pharmaceuticals.

Gillessen disclosed relationships with Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, InnoMedica, Ipsen, Macrogenics, MSD, Novartis, AdMe Tech Foundation, PeerVoice, Pfizer, Silvio Grasso Consulting, EPG Health, Intellisphere, and Gilead, as well as a patent/royalty/intellectual property interest.

Fizazi disclosed relationships with Amgen, Astellas, AstraZeneca, Bayer, Clovis, Daiichi Sankyo, Janssen, MSD, Novartis/AAA, Pfizer, Sanofi, Arvinas, CureVac, Macrogenics, and Orion.

Primary Source

European Society for Medical Oncology

Source Reference: opens in a new tab or windowGillessen S, et al "A randomized, multicenter, open-label phase III trial comparing enzalutamide vs a combination of radium-223 and enzalutamide in asymptomatic or mildly symptomatic patients with bone metastatic mCRPC" ESMO 2024;Abstract LBA1.

https://www.medpagetoday.com/meetingcoverage/esmo/111961

Prof Sends His 'What If Jan 6 Succeeded' Comic-Book To All Pa. High Schools

 by Dave Huber via The College Fix,

The Harvard Law professor who co-authored a “what if?”-style graphic novel about the January 6 “insurrection” succeeding is sending free copies to every public high school in Pennsylvania.

Alan Jenkins, formerly president of the Harvard “social justice communication lab” Opportunity Agenda, and his co-author Gan Golan are giving out gratis copies of  “1/6: A Graphic Novel” in order “to convey the risks facing American democracy,” The Philadelphia Inquirer reports.

“The forces that led to that insurrection … the white supremacy, disinformation […] are all very still much with us,” Jenkins said.

He added that he hopes students will see January 6 as “not unlike the 9/11 terrorist attacks.”

Jenkins said he chose Pennsylvania because it’s faced a lot of book “bans.” He noted it’s possible “1/6” might get banned “but [he’s] ready for that.”

“We think the truth always is stronger than censorship,” he added.

But one may wonder how a completely fictitious tale of alternative history counts as “truth.” Here’s a sample from “1/6’s” first issue, according to the Inquirer:

[…] a society controlled by armed militias who take over a TV network — declaring it to be “an enemy of freedom.” At a “patriots parade,” a speaker blasts the “thugs and criminals from Black Lives Matter” while adherents repeat white nationalist slogans, with the phrases “Blood and Soil” and “I will not be replaced” in word bubbles. Dissidents work covertly, avoiding the militias enforcing curfew while transporting Electoral College ballots — “the last evidence of our democracy.”

And were there Confederate flags flying around DC on Jan. 6? Jenkins’ book features it on top of the Capitol and Lincoln Memorial.

In the story’s second issue, “readers are taken through events leading up to and including Jan. 6 — starting with the 2017 [Charlottesville] ‘Unite the Right’ rally.” Jenkins’ “truth” includes the common — and devoid-of-context — Trump quote about “fine people on both sides” (Trump specifically condemned the neo-Nazis and white nationalists at the rally).

There’s also the missing-context phone calls to Georgia election officials in which Trump said “find 11,780 votes.”

Ironically, Jenkins (pictured below) said he expects “pushback” regarding the comic as many Pennsylvania parents have accused schools of “indoctrinating” students.

The state’s high schools also will receive a supplementary “action guide” for “1/6” which “lays out facts” about the insurrection, election “deniers,” increases in hate crimes, and legislators “banning” books —  “a hallmark of authoritarianism.”

Philadelphia-area schools did not respond to Inquirer queries about whether they would stock the book in their libraries or “how they would use it.” One district did note that “1/6” would first have to be reviewed by “a committee of librarians and administrators.”

Jenkins and Golan previously sent 150 copies to members of Congress who allegedly denied the 2020 election results.

According to his faculty page, Jenkins teaches courses on race and the law, communication, and Supreme Court jurisprudence. Along with his law degree, Jenkins has an MA in media studies and a BA in psychology and social relations.

https://www.zerohedge.com/political/professor-sends-his-what-if-jan-6-succeeded-comic-book-all-pennsylvania-high-schools

MSM Climate Alarmists Stumped After 'Boiling Oceans' Result In Very Quiet Hurricane Season

 Climate alarmist journalists at leftist corporate media outlets sounded the alarm early this hurricane season in the Atlantic and Caribbean region that "literal hot water" and "unprecedented ocean heat," fueled by "human-caused climate change," would unleash a very active and devastating hurricane season.

Yet, 3.5 months into hurricane season and peak season realized last week, John Shewchuk, a certified consulting meteorologist, wrote on X that the number of named storms in 2024 (as of Sept. 14) totals 7, compared with 20 at this exact point in 2020. 

So what happened to AP News, PBS, Vox, and other leftist corporate media outlets pushing climate doom headlines 24/7, igniting climate anxieties for America's heavily medicated population who believe the propaganda that Earth is doomed in several years unless fossil fuels are banned and more solar and windmills are purchased from China.

It's embarrassing for these woke media outlets to focus so much on imminent climate doom and, like Al Gore's climate prediction over the last several decades, never actually play out.

"Get used to it. Forecasters predicted months ago it was going to be a nasty year and now they are comparing it to record busy 1933 and deadly 2005 — the year of Katrina, Rita, Wilma and Dennis," AP journos wrote earlier this hurricane season, who tried to scare the hell out of readers. 

Shewchuk noted the low hurricane activity is "not unexpected" - because "Not only does global warming make the tropical atmosphere more stable, thus inhibiting tropical convection (https://wattsupwiththat.com/2024/04/08/global-warming-inhibits-hurrican…) -- but Tonga's unprecedented global warming spike further contributes to tropical suppression." 

Instead of focusing on cow farts and Taylor Swift's private jet, maybe, just maybe, it's time for corporate media to focus on the massive 2022 eruption of the underwater volcano in Tonga, known as Hunga Tonga-Hunga Ha'apai, that catapulted plumes of soot, water vapor, and sulfur dioxide into the stratosphere. It's likely been one of the major drivers in recent Earth's warming trends. To totally ignore this massive eruption demonstrates bias and agenda-driven within 'trust the science' leftist corporate media, as well as several federal agencies focused on weather. 

https://www.zerohedge.com/weather/msm-climate-alarmists-stumped-after-boiling-oceans-result-very-quiet-hurricane-season

"Results Could Take A While": NYT Primes Voters For Election Night Malarkey

 Some of us are old enough to remember that virtually every election in US history has been decided the same night - sometimes stretching into the wee hours, but we always woke up to the winner. That all changed in the 2020 'mail-in ballot' election, when several major Democrat cities stopped counting ballots at 9PM - in one instance because an alleged 'burst pipe' forced an evacuation in Fulton County, Georgia. Then there were ballot-counters in Detroit who covered windows with cardboard so that observers couldn't watch the count.

A brief review of election night malarkey from 2020:

• Fulton County, Georgia (Atlanta):

  • Fulton County, where Atlanta is located, temporarily paused counting ballots around 10:30 p.m. on Election Night due to a burst water pipe earlier in the day that delayed the processing of absentee ballots at the State Farm Arena. While there were initial reports that the counting had stopped, election officials clarified that counting continued but at a slower pace with some workers leaving for the night.

• Philadelphia, Pennsylvania:

  • Philadelphia, a critical city in Pennsylvania, saw intermittent pauses in the ballot-counting process. Officials announced they would stop counting for the night around 9 p.m. and resume the next morning. However, counting continued throughout the night at a reduced pace to process the large volume of mail-in and absentee ballots.

• Allegheny County, Pennsylvania (Pittsburgh):

  • Allegheny County also paused counting around midnight on Election Night due to a court order involving around 29,000 ballots that required special handling. Counting resumed the following day after the specific issue was resolved.

• Milwaukee County, Wisconsin:

  • Milwaukee, another key city, saw Donald Trump leading Joe Biden by 109,000 votes - until an overnight count of roughly 170,000 mail-in votes gave Biden a lead of 11,000 votes.

• Maricopa County, Arizona (Phoenix):

• In Maricopa County, GOP chairwoman Linda Brickman on Nov. 30 testified before members of the Arizona State Legislature that she personally observed votes for President Donald Trump being tallied as votes for Democratic presidential nominee Joe Biden when input into Dominion machines.

Now, the NY Times is preparing voters for more of the same - warning that thanks to more Americans using mail-in ballots, the "election results could take awhile," and that it may initially give the "false impression" that Donald Trump is the winner...

For the second straight presidential election, it is becoming increasingly likely that there will be no clear and immediate winner on election night and that early returns could give a false impression of who will ultimately prevail.

Large swaths of Americans have changed their voting habits in recent years, relying increasingly on mail-in ballots, which take more time to count than those cast in person on Election Day. States with prolonged vote-counting processes, such as Arizona, have become suddenly competitive. And the race between Vice President Kamala Harris and former President Donald J. Trump appears extremely close.

According to the Election Project, Democrats turned in 18 million mail-in ballots in the 2020 election vs. 10 million from Republicans in the 20 states that reported party registration by ballot. By the 2022 midterms, Democrats turned in 7.6 million ballots vs. 5.1 million from Republicans.

For this election, the Trump campaign and the RNC have begun a program called "Swamp the Vote" designed to encourage voters to cast early ballots - including by mail. The campaign has also released a memo warning of a "blue mirage," saying that "early Democrat leads in absentee and vote by mail are not at all predictive of victory on November 5th."

That said, last month at a Montana rally, Trump said "We want to go back to one-day voting and paper ballots."

According to pollster Nate Silver, Trump has a clear advantage over Harris. Until election night, we assume.

Battleground States

With the election just over 6 weeks away, two critical battleground states - Pennsylvania and Wisconsin - are facing potential delays in reporting full results.

Democrats have called for reforms to allow election officials to open and flatten ballots, known as "preprocessing," before the polls open on Election Day. State lawmakers have refused to budge.

According to the Times, the delays are likely to be most pronounced in the aforementioned cities of Philadelphia and Milwaukee, which are home to large numbers of Democratic voters. These cities could take longer to count their ballots than less populous counties simply due to the sheer volume of votes. Paulina Gutierrez, executive director of the Milwaukee Election Commission, estimates around 80,000 mail ballots in Milwaukee alone—up significantly from the 30,000 received during the midterms. "I will prioritize the security and the integrity of the election over speed any day," she said.

The slow vote-counting process means Wisconsin will not have full results on Election Night. Ann Jacobs, the Democratic chair of the Wisconsin Election Board, anticipates Milwaukee to finish counting at 3 a.m. or later. The potential delay in Pennsylvania is also raising concerns about premature assumptions of victory. As Michael McDonald, a political science professor at the University of Florida, explained, "In Wisconsin and Pennsylvania, that’s where we’re going to see the potential for this red mirage and the ballot dumps and all of those conspiracy theories that will arise from it."

Arizona and Nevada, two other battleground states, are also likely to face delays, although for different reasons. Both states rely heavily on mail-in voting. In the 2020 presidential race, Nevada wasn't called for Joe Biden until four days after the election, while Arizona took nine days. While both states allow local officials time to preprocess ballots, high voter turnout and the logistics of counting large numbers of mail-in ballots mean that a final call in either state could still take time.

Of course, it seems nothing can be done when Democrats engage in 'legal' election manipulation...

https://www.zerohedge.com/political/results-could-take-awhile-ny-times-primes-voters-election-night-malarkey

"Nothing Will Slow Me Down" - Trump Reacts As Reportedly Targeted By Shooter With AK47 While Golfing

 Update (1615ET): The former president has issued a statement confirming he is "safe and well" and declaring "nothing will slow me down"...

AP reports that the alleged shooter fled in an SUV and was later apprehended in a nearby county by local law enforcement, the officials said. The officials were not authorized to discuss the matter publicly and spoke on condition of anonymity about an ongoing investigation.

An AK-style firearm was recovered at the scene near Trump’s golf course, one of the officials and a third law enforcement official said.

The golf course was partially shut down for Trump as he played, and agents were a few holes ahead of him when they noticed the person with the firearm, the officials said.

The person appeared to push the muzzle of the rifle through the fence line and that’s when agents fired, the officials said

CNN reported that police have recovered a backpack and a GoPro camera.

They think the attempted Trump shooter wanted to film it.

The following clip shows a heavy police presence on the roads leading to the golf club...

*  *  *

The Trump campaign on Sunday said that former President Donald Trump is safe after reports of gunshots in his vicinity outside the Trump International Golf Course.

“President Trump is safe following gunshots in his vicinity,“ a brief statement released by Trump spokesman Steven Cheung said.

”No further details at this time.”

The U.S. Secret Service wrote on social media platform X that it is working with the Palm Beach County Sheriff’s Office to investigate the incident, adding that it occurred before 2 p.m. ET.

“The former president is safe,” the federal agency said.

The sheriff’s office will provide more details about the incident “soon,” the agency added.

CNN is reporting the shots were intended for the former president...

CNN goes on to report that a person has been detained in connection to the incident at Trump International Golf Club on Sunday, according to a law enforcement source.

Secret Service fired at the suspect, according to multiple sources.

A long gun (Don Jr confirmed it was an AK-47) has been recovered, according to the source.

Officials believe an armed individual intended to target former President Donald Trump at his golf club, according to sources briefed on the matter.

However, The New York Post said two people exchanged fire at Trump golf club in Florida, targeting each other (a narrative that has since been deleted).

The White House was quick to express their "relief" that Trump was not hit:

“The President and Vice President have been briefed about the security incident at the Trump International Golf Course, where former President Trump was golfing. They are relieved to know that he is safe. They will be kept regularly updated by their team.”

As the above suggests, no one is really sure WTF happened for now.

However, one thing we know for sure, the same rhetoric that likely prompted the first assassination attempt has not stopped...

Though, of course, everyone will quickly decry political violence...

...but, weren't we told that "words are violence" too?)

https://www.zerohedge.com/political/trump-safe-after-shooter-ak47-reportedly-targeted-former-pres-while-golfing-secret

John Jay rape saw ‘delayed response’ as school failed to notify NYPD, release any specifics

 A fiend sexually assaulted someone in a John Jay College of Criminal Justice restroom earlier this month, the school informed students Friday. 

The attack happened sometime during the week of Sept. 2 in a “restroom on college campus,” according to an email from the college titled “Clery Crime Alert/Timely Warning.”

“Crime alerts are posted in an effort to make John Jay College aware of any situation that poses a potential threat to the safety and well-being of those who live, work, attend and visit the campus,” the email states.

But the alert, required on campuses by the federal Clery Act, offered almost no specifics about the alleged crime, and didn’t say if the victim was male or female, or exactly when it happened. 

The act requires colleges to alert students to certain crimes.

The school’s fall semester started on Aug. 28.

A John Jay representative said the school is “actively investigating” the alleged incident.

“While we cannot comment on current investigations, the safety and well-being of our students remains our top priority, and we are committed to creating a safe campus environment for all members of our community,” they continued.

“Counseling and support services are available to students, faculty and staff affected by this incident.”

The NYPD apparently wasn’t notified about the incident, a police spokesman told The Post.

Several students on campus Saturday were caught off guard by the alert as well as how long it took for the college to release it, they said.

“It is pretty crazy that that happened here, especially since this is a criminal justice school,” said Jaylen Hernandez, a 19-year-old sophomore.

“It’s crazy too that I feel like they focus so much on, for example, when an alumni dies,” Hernandez said. “When an alumni dies, I get notifications on my phone from the school every time…and I’m like, [the sexual assault] happens and we didn’t know about it.”

Jason, left, listens to fellow freshman Arnold talk about the assault at the John Jay College of Criminal Justice.Aristide Economopoulos

A 22-year-old student, who got her undergraduate degree at Penn State, and just started working on her masters in forensics psychology at John Jay was disturbed by the attack. 

“I was shocked to see the email and see that that happened here — at a criminal justice college of all places — but I feel like sexual assault can happen anywhere unfortunately,” she said.

She called the college’s warning this week “a delayed response.”

“I know at my undergrad they would send the notice out right away,” she said.

“So when I saw it was from the first week of school I was like, ‘why are we just hearing about it now?'”

The school’s fall semester began a couple of days prior, on Aug. 28.Helayne Seidman

Other students took the alert in stride.

“We wish that didn’t happen, but it’s New York,” said Arnold, a 17-year-old freshman, who asked to remain anonymous. 

“I hope the school fixes this problem and any others like it so that this doesn’t happen again,” he said. “That’s kind of terrifying.” 

The freshman said he hadn’t seen the notice displayed anywhere on campus.

Heidy Velasquez, a 19-year-old sophomore, said faculty in her program held a mandatory meeting after the notification went out Friday and told students to come forward if they are victimized.

“‘If you ever have something happen to you, something inappropriate or that’s not consensual, you can come to us,” she said the faculty members said.

She was pleased the school was informing students about reporting sexual assaults but frustrated the notice came a week after the alleged attack.

“It’s frustrating,” she said, “because for a school this prestigious, they should say something immediately.”

https://nypost.com/2024/09/14/us-news/john-jay-students-were-shocked-by-the-sexual-assault-on-their-campus/