Originally published by our sister publication Specialty Pharmacy Continuum

By Gina Shaw
The evidence behind a boxed warning for thyroid cancer that has made many oncology clinicians wary of glucagon-like peptide-1 (GLP-1) receptor agonists is weaker than most practitioners realize, while emerging data suggest that these drugs may reduce cancer risk, experts said at HOPA 2026, in New Orleans. 

Meanwhile, patients are showing up to oncology clinics already on GLP-1s, forcing pharmacists to make real-time decisions about holding or continuing the drug during cancer treatment with almost no prospective data to guide them.

The boxed warnings for thyroid cancer “actually all come from animal studies; there’s never actually been a prospective clinical trial that has shown any kind of thyroid cancer signal in humans,” said Lindsay Mundy, PharmD, BCOP, a clinical oncology pharmacist specialist at Vanderbilt University Medical Center, in Nashville, Tennessee. 

Dr. Mundy added that the retrospective, cohort-based studies examining the question are subject to substantial detection bias, and the European Union removed the thyroid cancer warning from GLP-1 agents in 2023. “The U.S. has some opportunities to catch up to that,” she said.

Studies examining GLP-1s and cancer are mixed. For example, in a retrospective study by Hao et al, 43,317 individuals taking GLP-1RAs were compared with 43,315 matched nonusers. Taking GLP-1RAs was significantly associated with a reduced risk of overall cancer, particularly for endometrial, meningioma, and ovarian cancers; however, GLP-1RAs were associated with a nonsignificant increased risk of kidney cancer (JAMA Oncol 2025;11[10]:1186-1193).

Whether any protective signal reflects the drug itself or the weight loss it produces remains unresolved. 

“We really aren’t able to design a prospective randomized trial that would separate those things,” Dr. Mundy said. “It’s very hard to track weight over time on an individual basis.” 

There may also be metabolic and immune-modulating effects of GLP-1s independent of weight loss, she said, although the data on that are preliminary.

For patients already on a GLP-1 who are starting chemotherapy, the clinical concerns center on overlapping toxicities. “If you have someone on a highly emetogenic regimen and they come in mid-cycle saying that cycle was really hard—a lot of nausea, constipation, other GI side effects—my question is, is this the GLP-1 or is this the chemotherapy?” said Colleen McCabe, PharmD, BCOP, a clinical pharmacy specialist in sarcoma at Emory Healthcare, in Nashville. Her standard approach is to ask patients to hold the GLP-1 for the first few cycles. “If it’s truly coming from the chemotherapy, we need to make sure we’re managing that before adding something to muddy the picture,” Dr. McCabe said.

Weight loss during treatment adds another layer. Many IV regimens use weight-based dosing, and significant fluctuations that are common in sarcoma and head and neck cancers have dosing implications. “One hundred percent of my head and neck patients will end up with some kind of weight loss throughout their treatment,” Dr. Mundy said. “I already have weight loss as an issue. I really don’t need something else that [exacerbates] that.”

Oral targeted therapies raise a separate and underappreciated concern. A 2025 crossover study in 10 patients with ALK-positive non–small cell lung cancer found that coadministration of semaglutide reduced the area under the curve of alectinib (Alecensa, Genentech) by 32%, and after adding semaglutide, only 60% of patients maintained alectinib trough levels above the established efficacy threshold (Cancer Commun [Lond] 2025;45[8]:914-918). “When we’re talking about drugs with a narrow therapeutic index, a change in the absorption process is going to impact how much drug actually gets into the patient’s system,” Dr. Mundy said.

Shared decision-making is essential when assessing the merits and risks of GLP-1s in cancer patients, Dr. McCabe said. “What disease state is it? Are they curative intent or is this palliation? How invested is the patient in continuing the GLP-1? Is this something that’s really keeping their mental health together?”

Sarcoma patients on ifosfamide-containing regimens, in particular, tend to lose weight, Dr. Mundy noted. “I typically provide the guidance that we have had a lot of patients who come in on GLP-1s stop them in order to do chemotherapy and not had any weight gain. I also emphasize that we really see people struggle with nausea on these regimens and take the first couple of cycles to try to get this right and make sure it’s something they can tolerate. Profuse nausea and vomiting not only leads to weight loss, but it can also lead to electrolyte abnormalities and ER admissions.”

Dr. McCabe said the only times she has recommended continuing a chemotherapy patient on GLP-1s is with a “lighter” treatment regimen.

“Someone who was only on doxorubicin and we felt they’d be able to tolerate it; we might keep them on it. I had one patient, for example, for whom going off the GLP-1 would have caused significant distress because of how important the weight loss had been to her. Being able to give patients that sense of control and identity is still something that should be very highly valued, depending on the disease state and what data we have.”

There are limits to the available data on the impact of these drugs in the oncology setting, the experts stressed. “In a more common malignancy [such as] breast cancer, we might get clearer data one day,” Dr. McCabe said. “But in a cancer such as sarcoma, which is much less common, we’re probably never going to have that type of guidance.” What she hopes to see, she noted, is multisite, disease-specific collaborative research rather than small single-institution studies. “I would caution against small-scale studies really changing practice,” Dr. McCabe said. “But if we can start to collaborate across different institutions, we can get some pretty decent data.”

Dr. Mundy echoed the need for data-watching. “As these drugs become more mainstream, even small changes in cancer risk reduction could have a really drastic impact on oncology. This is something that is not going away anytime soon.”

Dr. McCabe reported that she has consulted for BMS. Dr. Mundy reported no relevant financial disclosures.