Key Ideas

Combining systemic immunotherapy with local, artery-directed treatment is improving outcomes in unresectable liver cancer eligible for embolization, though the specific local therapy used in the pivotal trial (TACE) differs from what most U.S. centers actually use (TARE). Separately, a large observational analysis raised a provocative signal that GLP-1 receptor agonists, already widely prescribed for diabetes and obesity, might be associated with reduced cancer progression across several tumor types, though this remains preliminary and requires prospective confirmation.

Adding Systemic Therapy to Liver-Directed Treatment

For more than two decades, transarterial chemoembolization (TACE) has been the standard of care for unresectable hepatocellular carcinoma (HCC) eligible for embolization, typically producing a median progression-free survival of eight to ten months. The STRIDE regimen (a single dose of tremelimumab combined with durvalumab) is already a frontline standard for advanced HCC, based on sustained overall survival benefit across multiple analyses. The phase 3 EMERALD-3 trial asked whether adding STRIDE, with or without the targeted agent lenvatinib, to TACE could improve on TACE alone in patients with embolization-eligible, unresectable HCC.

Both experimental arms improved progression-free survival compared with TACE alone: STRIDE plus lenvatinib plus TACE achieved a median of 13.0 months versus 9.8 months with TACE alone, and STRIDE plus TACE alone (without lenvatinib) achieved about 13 months as well, with the investigators concluding that STRIDE was the primary driver of benefit in the higher-risk population studied. Overall survival data remain immature, but early trends favor the combination arms, with some analyses suggesting STRIDE plus TACE without lenvatinib may have a modest edge on the overall survival trend over adding lenvatinib on top. Toxicity was manageable: the addition of lenvatinib increased rates of high blood pressure and diarrhea, and rare immune-related events occurred with the STRIDE regimen, but there were no unexpected safety signals overall.

Why Translating This to U.S. Practice Isn't Automatic

Although the NCCN lists TACE, TARE (transarterial radioembolization), and drug-eluting bead chemoembolization as acceptable local therapy options, U.S. practice has shifted heavily toward TARE, whose use rose from 22 percent to 51 percent of cases between 2016 and 2024, driven by data suggesting superior time to progression and higher rates of tumor necrosis. All of the positive trials combining immunotherapy with local therapy in HCC, including EMERALD-3, have used TACE as the local partner, and it remains genuinely unknown whether TARE produces the same synergy with immunotherapy, though there is separate evidence supporting synergy between radiation and immunotherapy more broadly. Several phase 2 studies combining radioembolization with immunotherapy are underway in the United States and may eventually answer this question directly. In the meantime, for the relatively small subset of U.S. patients who do receive TACE, incorporating systemic immunotherapy based on this positive trial data seems like a reasonable, evidence-supported extension of current practice, even though it isn't yet reflected in formal NCCN or FDA labeling for this specific combination.

A Provocative, Still-Preliminary Signal on GLP-1 Drugs and Cancer

Separately, one of the more talked-about presentations addressed a very different question: could GLP-1 receptor agonists, already used widely for diabetes and obesity, also affect cancer progression? A large observational analysis matched patients starting a GLP-1 receptor agonist after a stage I-III cancer diagnosis against patients starting a different diabetes medication class (DPP-4 inhibitors), across seven solid tumor types, and found a statistically significant reduction in progression to stage IV disease in four of them: lung, breast, colorectal, and liver cancer, with patients on GLP-1 drugs 38 to 50 percent less likely to progress to metastatic disease than those on the comparator medication. A separate look at tumor tissue data found that higher expression of the GLP-1 receptor on tumor cells independently predicted better overall survival, most notably in breast cancer.

This is genuinely interesting biology, and it builds on other observational studies this year reporting improved recurrence-free survival and lower all-cause mortality with GLP-1 drug use in patients with active breast and colon cancer. But it's important to be clear about the limits of this kind of evidence: all of it is retrospective and observational, meaning it cannot rule out that healthier patients, or patients with better-controlled diabetes and obesity, were simply more likely to be prescribed these drugs in the first place. No prospective randomized trial has tested this question, and none is currently underway, in part because GLP-1 drugs are already approved and widely used for other indications, reducing the financial incentive for a pharmaceutical company to fund a dedicated adjuvant cancer trial. For now, this should be understood as a hypothesis-generating signal rather than a reason to start a GLP-1 medication specifically for cancer control.

For Patients

If you or a loved one has unresectable liver cancer being treated with TACE, it's worth asking your oncology team whether adding systemic immunotherapy to that local treatment is appropriate, since this combination has now shown benefit in a large randomized trial, even though formal approval for this specific pairing is still pending. If your local treatment is TARE, which is more common in the United States, know that the evidence for adding immunotherapy in that specific context is less established, though it's an active area of research.

If you're taking a GLP-1 medication such as semaglutide or tirzepatide for diabetes or weight management and also have a cancer diagnosis, recent data suggest a possible association with better cancer outcomes, but this isn't yet proven, and you shouldn't start or stop this type of medication based on cancer-related expectations without discussing it with your full care team.

Key Takeaways

  • The phase 3 EMERALD-3 trial found that adding the STRIDE immunotherapy regimen (durvalumab plus tremelimumab), with or without lenvatinib, to TACE improved progression-free survival compared with TACE alone in embolization-eligible, unresectable hepatocellular carcinoma.

  • All positive immunotherapy-plus-local-therapy trials in this space have used TACE, not TARE, which is now the more commonly used local therapy in the United States, leaving an open question about whether the same benefit applies.

  • A large observational study found GLP-1 receptor agonist use after a cancer diagnosis was associated with reduced progression to metastatic disease in lung, breast, colorectal, and liver cancer, but this finding is preliminary and requires prospective validation.

  • Higher tumor expression of the GLP-1 receptor was independently associated with better overall survival, particularly in breast cancer, suggesting a possible direct biological link worth further study.

References

  1. Presented data on the phase 3 EMERALD-3 trial of STRIDE plus lenvatinib plus TACE versus TACE alone in unresectable hepatocellular carcinoma, 2026 ASCO Annual Meeting.

  2. Orland MD, Mandala A, Unlu S, et al. Can GLP-1 receptor agonists mitigate cancer progression? A propensity-matched analysis across seven solid tumors. Journal of Clinical Oncology, 2026;44(suppl 16):3143.