Blog

In an interim analysis of a phase II trial (SunRISe-4) reported in The Lancet Oncology, Necchi et al found that the addition of neoadjuvant TAR-200—a targeted releasing system that provides sustained delivery of gemcitabine within the bladder—to the PD-1 inhibitor cetrelimab resulted in a higher complete pathologic response rate compared with cetrelimab alone in patients with muscle-invasive bladder cancer who were ineligible for or declined neoadjuvant cisplatin-based chemotherapy.

Study Details

In the international open-label trial, 120 eligible patients with planned radical cystectomy were randomly assigned 5:3 between July 2022 and May 2024 to receive TAR-200 with gemcitabine at 225 mg plus cetrelimab at 360 mg every 21 days for four cycles (n = 79) or four cycles of cetrelimab at 360 mg every 21 days for four cycles (n = 41). The primary outcome measure was pathologic complete response in the efficacy-evaluable set; because not all patients had completed treatment at time of analysis, the efficacy-evaluable set was defined as all patients who had radical cystectomy or progressive disease or death before radical cystectomy.

Key Findings

Among patients in the efficacy-evaluable set, at a median follow-up of 23.5 weeks (interquartile range = 8.6–42.0 weeks), pathologic complete response was observed in 22 (42%, 95% confidence interval [CI] = 28%–56%) of 53 patients in the TAR-200/cetrelimab group vs 7 (23%, 95% CI = 10%–41%) of 31 in the cetrelimab group.

Rates of pathologic overall response (downstaging to ≤ ypT1N0 at radical cystectomy) were 60% vs 35%.

Treatment-related adverse events of any grade occurred in 72% of the TAR-200/cetrelimab group vs 44% of the cetrelimab group; grade ≥ 3 events occurred in 11% (most commonly hematuria, in 3%) vs 5% of patients. Serious treatment-related adverse events occurred in 11% vs 2% of patients. Treatment-related adverse events resulted in discontinuation of TAR-200 in 9% and cetrelimab in 8% in the TAR-200/cetrelimab group, with no discontinuations in the cetrelimab group. One treatment-related death was observed in the cetrelimab group (due to hyperglycemic, hyperosmolar, nonketotic syndrome).

The investigators concluded: “Neoadjuvant TAR-200 plus cetrelimab showed a high [pathologic] complete response rate with a manageable safety profile. These results support continued investigation of TAR-200 in patients with muscle-invasive bladder cancer planned for radical cystectomy.”

Andrea Necchi, MD, IRCCS, of San Raffaele Hospital, Milan, Italy, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Johnson & Johnson. For full disclosures of all study authors, visit thelancet.com.

A new meta-analysis research presented at the meeting of the American Neurological Association showed that timing of hormone replacement therapy for post-menopausal patients can affect risk of developing Alzheimer disease.¹ The study found that beginning hormone replacement therapy within 5 years of menopause can lower risk of Alzheimer development by 20 to 32%, and beginning hormone therapy at age 65 or later can increase the risk by up to 38%.

The meta-analysis included over 50 clinical trials and observational studies and compared women using hormone replacement therapy to a placebo/nontreatment group. The analysis looked at Alzheimer disease progression based on blood tests and brain imaging scans, studying the disease progression from initial mild cognitive impairment onward. The average age of individuals in these trials was 51. Overall, the analysis showed a 38% increase in risk of Alzheimer disease in women who began hormone replacement therapy at age 65 or older. The increased risk effect was particularly noticeable in women whose hormone therapy included progestin. Utilizing 45 observational studies, the meta-analysis found a 22% reduced risk of developing Alzheimer disease in women who started hormone replacement therapy nearer to the time of their menopause. From both groups of clinical and observational studies, investigators determined that individuals who started hormone replacement therapy within 5 years of beginning menopause had a 32% lower risk of developing Alzheimer disease.

Researchers indicated that hormone replacement therapy may be useful because it can provide the benefits of estrogen when the natural estrogen levels are dropping in menopause. With sustained estrogen, which is considered to assist in neural communications, inflammation may decrease and protect against cell damage that can lead to Alzheimer disease. On the other hand, if individuals start an estrogen hormone replacement regimen 10 or more years after menopause, inflammation may increase or place stress on the brain’s blood vessels due to potential early signs of Alzheimer disease like reduced blood flow or clumping of proteins.

“Starting hormone replacement therapy early may give the brain some protection, but if a woman already has Alzheimer’s or memory problems, hormone therapy won’t slow them down,” said FNU Vaibhav, MBBS, from Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, in a press release. “It’s like watering a plant: it helps when the plant is growing, but if it’s already wilting, it might be too late.”

Hormone therapy in this context is utilized by women post-menopause, usually to treat symptoms like hot flashes and sleep disturbances. Common forms include administration of estrogen alone, a combination of estrogen and progestin (synthetic progesterone), or estrogen and a selective estrogen receptor modulator. Hormone replacement therapies are often administered in pill or patch form, and are currently used by around 5% of women in the US.²

“The evidence isn’t strong enough to suggest hormone replacement therapy should be taken to prevent Alzheimer’s. However, if a woman is planning to use it for menopause symptoms, starting soon after menopause might give her brain some protection against Alzheimer’s disease later,” added Vaibhav. “She should talk to her doctor about stopping it after a few years to avoid raising her risk. And women should not start hormone replacement therapy in their 60s or 70s to protect their brain because it might do more harm than good.”

References

1. Timing of hormone replacement therapy may influence Alzheimer’s disease risk, study suggests. Press release. September 15, 2025. Accessed September 15, 2025. https://www.newswise.com/articles/timing-of-hormone-replacement-therapy-may-influence-alzheimer-s-disease-risk-study-suggests/?sc=dwhr&xy=5013482 

2. Anderer S. Only about 5% of US women now use menopausal hormone therapy. JAMA. 2024;332(21):1779.

Weed might nearly quadruple a person’s risk of developing type 2 diabetes, a new study says.

People who use cannabis have a 3.7 times greater risk of type 2 diabetes compared to the general population, researchers reported Monday at a meeting of the European Association for the Study of Diabetes in Vienna.

“As cannabis becomes more widely available and socially accepted, and legalized in various jurisdictions, it is essential to understand its potential health risks,” said lead researcher Dr. Ibrahim Kamel, chief resident at Boston Medical Center.

“These new sights from reliable real-world evidence highlight the importance of integrating diabetes risk awareness into substance use disorder treatment and counseling, as well as the need for health care professional to routinely talk to patients about cannabis use so that they can understand their overall diabetes risk and potential need for metabolic monitoring,” Kamel said in a news release.

For the new study, researchers analyzed data pooled from 54 health care organizations across the U.S. and Europe.

The team identified nearly 97,000 people between 18 and 50 years of age whose medical records reflected cannabis use ranging from occasional use to dependence.

They compared the weed users to more than 4.1 healthy people with no record of substance use. Both groups were followed for five years.

New cases of diabetes were significantly higher among cannabis users, with 1,937 cases compared to 518 in the healthy group.

Statistics showed the marijuana users at nearly four times greater risk of type 2 diabetes, researchers reported.

It might be that weed use affects a person’s blood sugar levels or insulin resistance, researchers said, or that people on cannabis eat in unhealthy ways that increase their diabetes risk.

However, researchers noted that the study cannot prove that weed use causes diabetes, but only shows an association between the two.

More research is needed to confirm these findings and better understand the relationship between cannabis and diabetes, including how weed might alter the effects of insulin in the body, researchers said.

Findings presented at medical meetings should be considered preliminary until published in a peer-reviewed journal.

More information

The U.S. Centers for Disease Control and Prevention has more on the health effects of marijuana.

Copyright © 2025 HealthDay. All rights reserved.