FDA Restricts Use of Immunotherapies in Gastric, Esophageal Cancers

 The FDA narrowed the indications for pembrolizumab (Keytruda)

opens in a new tab or window and nivolumab (Opdivo)opens in a new tab or window in gastric, gastroesophageal junction (GEJ), and esophageal cancers, according to letters sent to the respective drugmakers.

The agency had originally granted PD-L1 agnostic approval for the two immune checkpoint inhibitors as first-line treatment for advanced gastroesophageal cancers.

However, based on phase III trial data that became available since those initial approvals, the FDA's Oncologic Drugs Advisory Committee last year votedopens in a new tab or window that PD-1 inhibitors do not have a favorable risk/benefit profile in gastric/gastroesophageal junction (GEJ), and esophageal cancers with PD-L1 expression <1.

Now, nivolumab -- in combination with chemotherapy -- is indicated for the first-line treatment of adults with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC), and the treatment of adults with advanced or metastatic gastric cancer, GEJ, and esophageal adenocarcinoma whose tumors express PD-L1 ≥1.

In addition, approval for nivolumab plus ipilimumab (Yervoy) as first-line treatment of unresectable advanced or metastatic ESCC has been restricted to those with PD-L1 expression ≥1.

The change for pembrolizumab applies to two indications:

• The PD-1 inhibitor is now indicated in combination with chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors express PD-L1 ≥1.
• And pembrolizumab is now also indicated for patients with locally advanced or metastatic esophageal or GEJ adenocarcinoma that is not amenable to surgical resection or definitive chemoradiation in combination with chemotherapy for patients with tumors that express PD-L1 ≥1. (The checkpoint inhibitor is also approved for these patients as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 ≥10.)

In March, the FDA also granted full approvalopens in a new tab or window to pembrolizumab with trastuzumab (Herceptin) and chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma, but that was already for the PD-L1-positive subset.

https://www.medpagetoday.com/hematologyoncology/othercancers/116000

'Many Doctors Would Consider Assisted Dying at Their End of Life'

 

• More than half of surveyed physicians said they would consider assisted dying if faced with advanced cancer or severe Alzheimer's disease.
• Few doctors considered life-sustaining practices a good or very good option in advanced cancer or Alzheimer's.
• The survey involved over 1,100 doctors in five countries, including three U.S. states.

Many physicians said they would consider assisted dying if they were faced with advanced cancer or severe Alzheimer's disease, survey data showed.

In eight jurisdictions spanning five countries, about half of physicians would consider euthanasia a good or very good option if they had very painful end-stage cancer (54.2%) or severe end-stage Alzheimer's disease (51.5%), reported Sarah Mroz, PhD, of Vrije Universiteit Brussel in Belgium, and co-authors.

In the cancer situation, the proportion of physicians considering euthanasia a good or very good option ranged from 37.9% in Italy to 80.8% in Belgium. In the Alzheimer's scenario, the proportion ranged from 37.4% in the U.S. state of Georgia to 67.4% in Belgium, Mroz and colleagues said in the Journal of Medical Ethicsopens in a new tab or window.

Doctors who practiced in jurisdictions with legal options for both euthanasia and assisted dying were more likely to consider euthanasia in both the cancer (OR 3.1, 95% CI 2.2-4.4) and Alzheimer's (OR 1.9, 95% CI 1.4-2.6) situations. In the cancer scenario, 33.5% of doctors said they would consider drugs at their disposal to end their own life.

"Over half of the physicians surveyed would consider assisted dying for themselves, with their attitudes shaped by their specialty and whether they practice in a jurisdiction where it is legally available," Mroz said.

"This is notable and confirms prior research showing that acceptance of assisted dying increases following its legalization," she told MedPage Today.

The survey also showed that few doctors considered life-sustaining practices a good or very good option in advanced cancer or Alzheimer's; less than 1% wanted cardiopulmonary resuscitation (CPR) or mechanical ventilation, and less than 4% wanted tube feeding.

"This is in line of what we know: that most physicians wouldn't want aggressive end-of-life care, whether it's CPR or intubation, and would consider even more intensive ways to relieve suffering at the very end of life," observed geriatrician Eric Widera, MD, of the University of California San Francisco, who wasn't involved with the study.

"This is in contrast to the increasing use of certain life-sustaining treatments like invasive mechanical ventilation in diseases like advanced dementia without a clear mortality benefit of doing so," he told MedPage Today.

More than 91% of survey respondents considered intensifying symptom relief a good or very good option. Just over half considered palliative sedation a good or very good option; those who considered palliative sedation for Alzheimer's disease ranged from 39.3% in Georgia to 66.3% in Italy.

In 2022 and 2023, Mroz and colleagues surveyed 1,157 doctors in eight jurisdictions with differing laws and attitudes about assisted death: Belgium; Italy; Canada; the U.S. states of Oregon, Wisconsin, and Georgia; and the Australian states of Victoria and Queensland. Two hypothetical situations were presented to probe doctors' views about end-of-life care.

In the cancer scenario, doctors assumed they had extensive lung and bone metastases; their treating oncologist had said no further treatments were available and their estimated life expectancy was no more than 2 weeks. In the Alzheimer's situation, doctors assumed they no longer recognized their family or friends; they had refused to eat or drink, and it was no longer possible to communicate with them about treatment options.

In Oregon, physician-assisted dying has been legal since 1997. Medical aid in dying requires the capacity to consent and a patient must have an incurable or irreversible disease that would result in death within 6 months, so the Alzheimer's scenario would not be realistic there. Physician-assisted dying is illegal in Wisconsin and Georgia.

In Canada, both physician-assisted dying and euthanasia have been allowed since 2016. Assisted dying has been legal in Belgium since 2002, but it is illegal in Italy. In Australia, Victoria implemented assisted dying legislation in 2019. Queensland passed legislation in 2021, but it was not in place when the survey was conducted.

Opposition to medical aid in dying laws used to come from three groups in the U.S., noted ethicist Arthur Caplan, PhD, of the NYU Grossman School of Medicine.

"There was religious opposition, mainly led by the Catholic Church," he said. The disability community also voiced concerns "and doctors -- the [American Medical Association] and other medical organizations -- were very firm in opposing legalization, particularly at the state medical society level," Caplan told MedPage Today.

"The opposition still has a religious component and a disability component, but the medical profession is shifting in the U.S. -- not necessarily to come out and support medical aid in dying, but it's moving toward neutrality," he continued. "It's the older generation that opposes legalization. As younger doctors begin to take over and move into more powerful positions, they are not as opposed. That shift is somewhat reflected in this survey."

The survey included general practitioners, palliative care doctors, and medical specialists highly likely to treat patients at the end of their life like cardiologists, emergency medicine doctors, oncologists, neurologists, and intensive care specialists. While sex, age, and ethnicity did not appear to influence preferences for end-of-life practices, prevailing legislation in a doctor's jurisdiction did.

Several ethical considerations arise from the study findings, Mroz and colleagues said. Previous work has suggested a link between physicians' consideration of their own end of life and their clinical practice, they pointed out.

But most physicians do not want to impose their values on other people, noted Gary Gala, MD, of UNC Health in Chapel Hill. "It's a rare thing in my career experience to see that," he said.

"On the other hand, so many patients and families ask: What would you do, doc? What would you do in this situation? Sometimes it's helpful for patients and families to understand a physician's perspective while not overwhelming them with your own values."

Disclosures

This study was funded by Vrije Universiteit Brussel and Ghent University.

Mroz and co-authors reported no conflicts of interest.

Widera, Caplan, and Gala reported no disclosures.

Primary Source

Journal of Medical Ethics

Source Reference: opens in a new tab or windowMroz S, et al "Physicians' preferences for their own end-of- life: a comparison across North America, Europe, and Australia" J Med Ethics 2025; DOI: 10.1136/jme-2024-110192.

https://www.medpagetoday.com/neurology/alzheimersdisease/116005

Groundbreaking Insurance Reform Is Buried In The One Big, Beautiful Bill

 by Sally Pipes

There are more than 40 healthcare provisions in the One Big Beautiful Bill Act (OBBBA) that passed the House of Representatives by a one-vote margin last month. One, in particular, deserves more attention than it is getting.

The legislative package would codify and expand Individual Coverage Health Reimbursement Arrangements, which the first Trump administration introduced in 2019. ICHRAs allow employers to give workers untaxed dollars, which they can use to purchase health insurance on the individual market.

In many ways, ICHRAs are the health insurance equivalent of retirement accounts to which employers make defined contributions. These accounts have the potential to make health insurance more accessible and affordable for not just employees but employers, too.

As the Manhattan Institute’s Chris Pope notes in a recent study on ICHRAs, 117 million Americans between the ages of 19 and 64 received insurance from employers in 2023. Just 16 million bought insurance on the individual market.

In some ways, this makes sense. Employer-sponsored health insurance is familiar. Enrolling in an employer plan spares workers the hassle of having to navigate the individual market.

But today, health insurance is actually cheaper on the individual market than when purchased by employers.

So employers embracing ICHRAs could save themselves and their employees a lot of money.

And by putting individuals in charge of their own health insurance needs, ICHRAs can unleash the kind of market forces that help drive down costs and improve value in every other sector of the economy.

People are more responsive to market signals when they are enrolled in individual market plans. One study found that a 1% premium increase leads to a 1.7% drop in individual market plan enrollment. By contrast, a 1% premium increase in the employer market causes enrollment to drop by between 0.2% and 0.8%.

This finding reveals one of the main problems with employer-sponsored insurance—it obscures the cost of health coverage. Employees have no incentive to seek out more affordable providers or services when someone else is paying the bill.

Providers are aware of this market dynamic, which means they are constantly, as Pope puts it, “needlessly inflating costs.” That’s why, he goes on to note, “Starbucks spends more on health care for its workers than it does on coffee.”

Increased adoption of ICHRAs would disrupt this status quo. Employers’ costs would decline. Employees spending their ICHRA money would have a strong incentive to pick a health plan that suits their needs and budget, rather than the one-size-fits-all plan that most employers offer now.

And by putting consumers in charge of their own healthcare dollars, ICHRAs could foster the kind of competition among both insurers and providers that drives down costs and improves value over the long term. One study found that expanding the number of plan options for employees can provide benefits equal to 13% of premiums.

Decoupling health insurance and employment has a number of downstream benefits for workers of all stripes.

For instance, it encourages entrepreneurship by giving people the security to leave their jobs without fear of losing health coverage. And it offers a suitable coverage option for part-time workers, only 26% of whom currently receive health insurance from their employers.

ICHRAs could also make it more financially realistic for small businesses to offer health benefits. Just 56% of those who work for firms with fewer than 50 employees get an offer of insurance through their jobs. Cost is typically the chief impediment. ICHRAs would help remove that barrier.

These accounts have only been around for five years. But Americans are waking up to their benefits. Around 500,000 people were enrolled in ICHRAs in 2023. The nonpartisan Congressional Budget Office estimates that around 2 million workers will be enrolled in these plans by 2032.

And that’s if nothing else changes. If the big, beautiful bill passes as written, it will rebrand ICHRAs as CHOICE plans—a less confusing acronym that experts hope will encourage more businesses to adopt them.

After codifying Trump’s ICHRA rule in law, lawmakers could consider something like Pope’s proposal for a Worker’s Choice ICHRA, which would allow employers to offer both ICHRAs and traditional insurance plans by guaranteeing coverage parity between the options.

Americans deserve more choice in their health benefits. Expanding access to ICHRAs would give it to them.

https://www.forbes.com/sites/sallypipes/2025/06/09/this-groundbreaking-insurance-reform-is-buried-in-the-one-big-beautiful-bill/