A new oncology drug endpoint, based on what’s known as minimal residual disease, gained the backing of FDA advisors, potentially opening the door to new trial designs for blood cancer drugs.
An FDA advisory committee voted unanimously on Friday that evidence supports a new intermediate endpoint for accelerated approvals in multiple myeloma.
Patients who took an angiotensin-converting enzyme (ACE) inhibitor while undergoing cancer treatment with high-dose anthracycline chemotherapy did not show any difference in troponin T levels, a biomarker associated with heart damage, at one month after their last chemotherapy dose compared with those who did not take an ACE inhibitor, according to a study presented at the American College of Cardiology’s Annual Scientific Session.
The PROACT study reported no impact on cardiotoxicity biomarkers or secondary endpoints related to heart function among patients who took high doses of enalapril, an ACE inhibitor, along with high doses of anthracyclines.
“We did not see evidence that we could reduce this biomarker of cardiotoxicity during chemotherapy [with an ACE inhibitor],” said David Austin, MD, consultant cardiologist at the academic cardiovascular unit in James Cook University Hospital, South Tees, Middlesbrough, United Kingdom, and the study’s lead author. “The conclusion from PROACT is that we would not support the adoption of putting enalapril into a standard care preventative pathway in these patients.”
Anthracyclines are a well-established class of cancer drugs that are used to treat several types of cancer. While they are effective at eradicating cancer, they are known to carry a risk of causing damage to the heart muscle. In a small proportion of cases, this cardiotoxicity ultimately leads to heart failure, a condition in which the heart muscle becomes too weak or too stiff to effectively pump blood throughout the body. Previous studies have shown the release of troponin—a group of proteins expressed only by heart muscle cells—during chemotherapy to be a biomarker that is indicative of a higher likelihood of changes in heart function that can lead to symptomatic heart failure later.
To determine whether ACE inhibitors could help to prevent cardiotoxicity, researchers enrolled 111 patients undergoing treatment for breast cancer or non-Hodgkin lymphoma at 13 sites in the U.K. Half of the patients were randomized to receive enalapril and half did not receive enalapril while undergoing chemotherapy. Researchers assessed participants’ troponin levels during their chemotherapy treatment and at one month following their last anthracycline dose.
The study participants were an average of 57 years old and 78% were women; 62% had breast cancer and 38% had non-Hodgkin lymphoma. All patients had negative troponin results at the start of the study, indicating no baseline heart damage. During their cancer treatment, participants received anthracyclines at a mean dose of 328mg/m2 doxorubicin-equivalent. The mean dose of enalapril among those who were randomized to take the ACE inhibitor was 17.7mg.
At the end of the study period, there was no significant between-group difference in the proportion of patients who had experienced a troponin T release, the study’s primary endpoint, which occurred in about 77.8% of those who received enalapril and 83.3% of those receiving standard of care.
There was also no significant difference between groups in terms of troponin I, another type of troponin. However, the researchers said the proportion of patients testing positive for troponin I—47% among those receiving enalapril and 45% among those receiving standard of care—was substantially lower in both groups compared with the proportion testing positive for troponin T.
“That finding itself has implications because guidelines don’t currently differentiate based on type of troponin,” Austin said. “Both have been shown to be associated with cardiotoxicity in observational studies. I was surprised by the difference, and I think this raises the question of what troponin we should be using.”
Outcomes among the two study groups were also similar in terms of left ventricular ejection fraction and left ventricle global longitudinal strain, which are measured with an echocardiogram and used to assess heart function.
Based on the findings, researchers said ACE inhibitors are not likely to play a role in future efforts to prevent cardiotoxicity associated with anthracyclines.
“The field probably needs to find another [drug] candidate before starting again on another preventative study,” Austin said.
The PROACT study will continue to track outcomes in the study participants for at least 12 months.
The study was funded by National Institute for Health and Care Research.
Francis S. Collins, MD, PhD, a renowned physician-geneticist and former director of the NIH, revealed he has prostate cancer.
In a perspective piece published in the Washington Post, Collins said he went public to "share lifesaving information, and I want all men to benefit from the medical research to which I've devoted my career and that is now guiding my care."
Collins, 73, explained that 5 years ago his doctor had noted a slow rise in his prostate-specific antigen (PSA) level. A targeted biopsy then identified he had a slow-growing cancer and he was referred to active surveillance.
However, a month ago, his PSA level shot up to 22 ng/mL, well above the normal level of 5 ng/mL for an individual his age. An MRI showed that the tumor had significantly grown, and new biopsies showed that it had transformed into a much more aggressive cancer, with a Gleason score of 9.
Thus, a PET scan ordered to determine if the cancer had spread beyond the prostate "carried high significance," he wrote. "Would a cure still be possible, or would it be time to get my affairs in order?"
He noted that the 5-year survival rate for prostate cancer that has metastasized to other parts of the body is just 34%.
Fortunately, the scan showed the cancer had not spread outside the primary tumor, and he is scheduled to undergo a radical prostatectomy, which his doctors said has a high likelihood of being curative.
Collins said that advances in research and technology -- like high-resolution MRI that can detect the exact location of a tumor, or the robotic surgery he'll be undergoing that is less invasive than previous surgical approaches -- mean that prostate cancer can now be treated with "individualized precision and improved outcomes."
"Having now received a diagnosis of aggressive prostate cancer and feeling grateful for all the ways I have benefitted from research advances, I feel compelled to tell this story openly," he wrote. "I hope it helps someone. I don't want to waste time."
Early detection really matters, he added, and when combined with active surveillance, can identity those high-risk cancers like his, while leaving others alone.
However, he also observed that current screening guidelines can leave men and their physicians confused.
The U.S. Preventive Services Task Force (USPSTF) 2018 recommendations suggested that men ages 55 to 69 discuss PSA screening with their physicians, but advised against screening once men hit the age of 70. This was a change from the 2012 guideline in which the USPSTF recommended against PSA screening entirely -- a policy that has been linked with a rise in the incidence of advanced prostate cancer in the U.S.
On the other hand, the American Urological Association and Society for Urologic Oncology suggest that screening should begin earlier -- especially for men like Collins with a family history of prostate cancer, and African-American men who have a higher prostate cancer risk.
Collins' decision to disclose his diagnosis was met with praise by members of the healthcare community.
"Francis Collins' bravery in revealing his prostate cancer diagnosis inspires us all," said Ellen Sigal, PhD, chair and founder of Friends of Cancer Research, in a statement. "His dedication to health and medical research has touched countless lives, and I am confident that his strength and resilience will guide him through this journey. We, and millions of patients whose lives he has changed, stand with him in support and hope, ready to fight alongside him."
HHS Secretary Xavier Becerra, said that "Dr. Collins has saved millions of lives and inspired generations of doctors and scientists in his career. For him, an obstacle is but an opportunity to teach. He has always sparked confidence in humankind's ingenuity to defeat our Goliaths. Prostate cancer will soon learn that lesson, I'm sure."
https://www.medpagetoday.com/hematologyoncology/prostatecancer/109646
Republican lawmakers tore into FDA Commissioner Robert Califf, MD, over the agency's handling of everything from the infant formula shortage crisis to the authorization of COVID-19 vaccines during a hearing of the House Committee on Oversight and Accountability on Thursday.
"Unfortunately, the FDA under President Biden is suffering from dysfunction and failing to do the bare minimum to carry out its core mission, which is to make certain our nation's food and drug products are safe and effective," said Committee Chair Rep. James Comer (R-Ky.) in his opening remarks.
COVID Vaccines, Ivermectin
During the hearing, Rep. Paul Gosar (R-Ariz.) said that "obviously the FDA made a mistake in granting the emergency use authorization and license of COVID-19 vaccines," which he noted do not stop transmission of the virus and have been linked to injuries and deaths reported to the Vaccine Adverse Event Reporting System.
"As head of the FDA, would you like to take an opportunity to express your regret in failing to curtail the chronic disease epidemic in America?" Gosar asked.
Califf explained that the initial COVID vaccine trials, upon which emergency use authorizations were based, showed a "dramatic reduction" in infection rates, but then the virus mutated.
And there is still evidence to demonstrate that "if you live in a county with a higher vaccine rate, the mortality rate is lower," Califf said. "So, when you compare the two, yes, vaccines have side effects, [but] the risk of being dead is lower if you're vaccinated."
Gosar also criticized the FDA's "years-long smear campaign against ivermectin," but Califf said that randomized trials have found no benefit from ivermectin for treating COVID-19.
"What we're not doing is telling doctors what they have to do. Doctors have the right to prescribe ivermectin off-label," he added.
Infant Formula Shortage Response
Regarding the infant formula shortage crisis, Comer argued that the FDA had tried to use the COVID-19 pandemic as a cover for "neglecting facility inspections and justifying poor performance."
Rep. Lisa McClain (R-Mich.), who spearheaded an investigation into the shortages, asked Califf a series of questions regarding who at the agency and at the White House knew about the potential for a shortage and when.
Califf, who was confirmed to the post of FDA commissioner on Feb. 14, 2022, said he was aware that day that a manufacturer responsible for 40% of the nation's infant formula had voluntarily recalled products made at one of its plants, as it happened the day of his confirmation.
McClain argued that, based on internal emails that her committee obtained, FDA officials were discussing infant formula supply issues as far back as February 4 of that year.
"Why did it take 3 months for President Biden to invoke the Defense Protection Act?" McClain asked, asserting that either the FDA didn't tell the president about the shortage or the president didn't act.
Califf said McClain had the emails and he could not comment further.
Committee Ranking Member Rep. Jamie Raskin (D-Md.) said Congress passed a bipartisan bill to respond to such shortages, but a second bill meant to strengthen FDA's oversight to help prevent shortages was rejected by over 200 Republicans.
Food Inspections
Raskin also lauded the agency's quick response to the finding of lead in applesauce packets, which were recalled in November 2023. The lead contamination was later found to be tied to a cinnamon processor in Ecuador.
Asked why the FDA can't inspect every private manufacturing facility, of which there are roughly 280,000, Califf likened the agency to a set of referees and industry to the player or "first line of defense." Congress "writes the rule book," he said.
While the FDA doesn't have the budget to inspect all private facilities, it can require the manufacturers to do the testing themselves, as is the case for drugs. With regard to the tainted applesauce, "if there had been mandatory testing when it got imported into the U.S. from Ecuador, the stores that were selling it probably would have picked it up at that point," Califf said.
https://www.medpagetoday.com/publichealthpolicy/fdageneral/109657
President Biden warned Friday that the expected attack Iran is planning on Israel could happen soon.
When asked about how imminent the attack on Israel may be, Biden said he didn’t want to get into classified information and added his “expectation is sooner than later.”
He also replied “don’t” when asked for his message to Iran.
“We are devoted to the defense of Israel,” the president added. “We will support Israel and help defend Israel, and Iran will not succeed.”
U.S. officials have sounded the alarm this week that Iran is expected to launch a retaliatory attack on Israel in response to an April 1 attack on its embassy in Syria. The suspected Israeli attack killed seven Iranian military advisers, including three senior members of Iran’s Islamic Revolutionary Guard Corps.
White House national security communications adviser John Kirby told reporters earlier Friday that the Iranian threat is “viable.”
“We’re watching it very, very closely,” he said, adding that the U.S. will “continue to stay in close touch with our Israeli counterparts about preparations for this threat.”
The State Department also issued updated security warnings for U.S. government employees in Israel, restricting them and their families from personal travel outside of the greater Tel Aviv area, Jerusalem and the southern city of Be’er Sheva.
https://thehill.com/homenews/administration/4590791-biden-warns-iran-attack-on-israel-may-be-soon/
President Biden on Friday warned about the “extreme voices” in the country he said are targeting Black Americans.
During virtual remarks at the National Action Network Convention, the president said there are threats to turn back the clock on civil rights.
“There are real threats we face. The more extreme voices out there who simply don’t want to see people of color in the future of our country, they want to turn back the clock — voter suppression, election suppression, ripping away reproductive freedom … affirmative action, gutting it,” Biden said.
“And attacking diversity across American life. Banning books — this is 2024, banning books, attempting to erase history, embracing political violence like what happened on Jan. 6. These extremists are determined to erase the progress we’ve made, but together, we are determined to make history, not erase it,” he added.
He listed policies that he called “transformational change” under his administration, including providing $76 billion in federal contracts to small, disadvantaged businesses, providing tax credit for first time homebuyers and curbing bias in home appraisal process.
He also noted that more Black Americans have health insurance than ever before, more Black businesses are starting up than seen in the past 25 years, and Black wealth is up 60 percent.
The president told the convention that he sees an America “where we defend democracy, we don’t diminish it.” He said he wants a future where he would sign into law the John Lewis Voting Rights Act, the George Floyd Justice in Policing Act and a bill to codify Roe v. Wade — all legislation that would likely take a Democratic majority in the House and Senate.
Biden was introduced by the Rev. Al Sharpton and spoke to the National Action Network Convention as he has been looking to court Black voters in order to rebuild the coalition that brought him the White House in 2020.
A The Wall Street Journal survey this week found that Biden’s support amongst Black voters in seven swing states has dipped when compared to the last election cycle and that 30 percent of Black men in swing states said they would likely support former President Trump.
The Democratic National Committee used campaign funds to cover more than $1.5 million in legal costs incurred by President Biden during the investigation into his mishandling of classified documents — while attacking Donald Trump for using the same mechanism to pay his attorney fees, Federal Election Commission records reviewed by The Post show.
The sum was used to pay for lawyers and firms representing the president during special counsel Robert Hur’s 13-month investigation, which wrapped up in February. The payments were first reported by Axios.
On Feb. 8, Hur released a 388-page report in which he explained his decision not to pursue charges against the president, arguing that Biden would likely present himself at trial as a “well-meaning, elderly man with a poor memory,” making a conviction unlikely.
During the investigation, the DNC paid $1.05 million to Bob Bauer PLLC, the professional limited liability company belonging to top Biden attorney Bob Bauer, who is married to senior White House communications adviser Anita Dunn.
That money was partly used to bring on heavy-hitting lawyer David Laufman, a former Justice Department official who worked on the investigation of Hillary Clinton’s use of a private email server while she was secretary of state — as well as the probe into Russian meddling in the 2016 election.
The DNC also paid upwards of $100,000 to Boston law firm Hemenway & Barnes, professional home to Biden attorney Jennifer Miller. It’s unclear how much of that money related to Miller’s work on the Biden documents case.
The DNC and the Biden 2024 campaign have vehemently attacked the presumptive GOP nominee for using campaign funds to cover his mounting legal expenses — and tapping grassroots donors to do so.
The Biden campaign has accused Trump of using a mega-fundraiser held in Palm Beach on April 6 to defray his attorney costs rather than focus on electioneering, claiming the former president is using “billionaire-reliant funds it has to pay off his various legal fees.”
“We are not spending money on legal bills. We are not hawking gold sneakers or any of that stuff. The money that we are raising, we are going straight to talking to voters,” Rufus Gifford, the Biden campaign’s finance chair, told MSNBC last week.
Given the past criticism of Trump’s use of campaign funds to cover his bills, the DNC debated whether it would be a good idea to do the same for Biden, Axios reported, citing a source familiar.
But Trump-affiliated groups have used a far larger share of funds to cover the 45th president’s legal expenses.
The 77-year-old’s team has used more than $50 million in political action committee funds, coming from the Save America and Make America Great Again Inc. PACs, to pay down legal bills related to four ongoing criminal cases against Trump.
The Republican National Committee has insisted Trump’s campaign has not asked for the official GOP to cover the former president’s legal bills, but the funding situation has gotten so dire in the past for Save America that it requested a $60 million refund this past summer of money it had siphoned off to MAGA Inc.
“There is no comparison — the DNC does not spend a single penny of grassroots donors’ money on legal bills, unlike Donald Trump, who actively solicits legal fees from his supporters and has drawn down every bank account he can get his hands on like a personal piggy bank,” DNC spokesperson Alex Floyd said in a statement.
“While Donald Trump is beleaguered and broke as a consequence of his mounting legal troubles, President Biden is leading a campaign and Democratic Party that is opening offices in battleground states, recruiting thousands of volunteers, and making smart investments in the campaign infrastructure to win in November. ”
Trump’s team hit back at what it called the Biden campaign’s “hypocrisy.”
“Joe Biden and the Democrats’ entire campaign against President Trump is based upon lies and hypocrisy — they have repeatedly stated they don’t spend money on Biden’s legal bills while they attack President Trump for having to defend himself from Biden’s witch hunts,” Trump 2024 national spokesperson Karoline Leavitt said in a statement to The Post.
“Come to find out, the DNC paid millions to cover Biden’s legal bills to a law firm run by the husband of top White House staffer Anita Dunn. Apparently ‘10% for the big guy’ from Hunter wasn’t enough for Crooked Joe to foot his own bill.”
https://nypost.com/2024/04/12/us-news/dnc-paid-for-bidens-legal-bills-in-classified-documents-case/
