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Immunotherapy with single tremelimumab regular interval durvalumab (STRIDE) treatment plus trans-arterial chemoembolization (TACE) was associated with longer progression-free survival among people with unresectable embolization-eligible hepatocellular carcinoma (HCC) than TACE alone, new research found.

Another group of participants in the study who received STRIDE, TACE, and the TKI lenvatinib also saw an improvement in progression-free survival compared with those who received TACE alone; however, only a minority of these participants saw a progression-free survival benefit compared with those who received STRIDE plus TACE.

“EMERALD-3 is the first phase 3 trial to demonstrate a STRIDE-based regimen improves clinical outcomes when combined with TACE, which supports its role as a potential new treatment option in unresectable embolization-eligible HCC,” said study co-investigator Ghassan K. Abou-Alfa, MD, JD, MBA, during a news briefing at the American Society of Clinical Oncology (ASCO) 2026.

Although the overall survival data were only 40% mature, Abou-Alfa, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, noted that it was trending in a favorable direction for STRIDE plus TACE over TACE alone in an interim analysis. He called the difference “clinically meaningful.”

“It appears to be that, as of tomorrow, STRIDE plus TACE is an appropriate standard of care,” he added.

Putting Results in Context

TACE is very commonly used worldwide — approximately one third of people with HCC are appropriate candidates for the procedure. However, the intervention is associated with only an average progression-free survival of 8-10 months. STRIDE, which was approved by the FDA in 2022, is standard-of-care for unresectable advanced HCC, the study authors noted in their abstract.

In the current study, Abou-Alfa, lead author Masatoshi Kudo, and colleagues randomly assigned 760 adults with pathologically or radiologically confirmed HCC to one of the three groups. One group received STRIDE, lenvatinib, and TACE (n = 293); another received STRIDE and TACE (n = 175); and a third group of participants received TACE alone (n = 292).

Baseline characteristics were broadly balanced across groups. Treatment continued for 24 months, with progression-free survival assessed up to 36 months or until disease progressed, or patients experienced unacceptable toxicity or withdrew consent.

The primary endpoint was progression-free survival between the triple intervention group vs TACE. Secondary endpoints included overall survival differences between certain groups.

Key Findings

The triple intervention group showed a statistically significant improvement in progression-free survival with a median of 13.0 months vs a median of 9.8 months in the TACE only group (hazard ratio [HR], 0.70; P = .0007), as well as a positive overall survival trend (HR, 0.84; P = .1814).

The combined STRIDE plus TACE cohort also showed improved progression-free survival (12.9 months vs 8.1 months; HR, 0.71; P = .0062) and overall survival vs TACE alone (HR, 0.70).

That the combination “showed clinically meaningful improvements in progression-free survival and overall survival vs TACE alone” suggests that STRIDE is the driver of efficacy in the intention-to-treat population, said Abou-Alfa.

The subset of patients in the triple intervention group who saw a progression-free survival benefit over STRIDE plus TACE were people in Japan with liver cancer of a nonviral etiology.

The additional treatment came at the cost of more toxicity, noted invited study commenter Steven L. Chan, MD, a professor in the Department of Clinical Oncology at The Chinese University of Hong Kong, Hong Kong, China, who suggested lenvatinib be held for subsequent therapy to lessen the initial toxicity.

The EMERALD-3 trial strengthens the findings in the literature that favor immunotherapy plus TACE to improve progression-free survival. Four other major phase 3 trials evaluating immune checkpoint inhibitors vs TACE for people with unresectable embolization-eligible HCC include EMERALD-1, LEAP-012, TALENTACE, and the camrelizumab plus rivoceranib study (the results of which were also presented at ASCO 2026).

“All of these studies reproduce the improvement of progression-free survival,” Chan said. He also noted the HR across all five trials ranged between 0.6 and 0.7, so there could be a class effect.

Safety Signals

Adverse events “were exactly as expected per arm,” said Abou-Alfa. “The safety profile was acceptable and consistent with the known safety profiles of STRIDE, lenvatinib, and TACE.”

The most common adverse events of any grade in the triple therapy group were hypothyroidism, hypertension, and diarrhea; in the STRIDE plus TACE group they were postembolization syndrome, pyrexia, and hypothyroidism; and in the TACE only group they were postembolization syndrome, pyrexia, and constipation.

The incidence of treatment-related adverse events of maximum grade 3 or grade 4 was 62.7% for the triple intervention group, 48.6% for STRIDE plus TACE group, and 18.6% with TACE alone.

An adverse event leading to discontinuation was 36% for the triple therapy group, 21% for the STRIDE and TACE group, and N/A for the TACE only group.

Additional Toxicities a Concern

“There’s a major unmet need in intermediate HCC. We have a plethora of regimens for advanced HCC,” but not for this subset of patients, said Vishwanath Sathyanarayan, an ASCO expert in liver cancer and medical oncologist at Rangadore Memorial Hospital Bengaluru, India, who was invited to comment on the trial during the press briefing.

Sathyanarayan said there was a very good rationale to explore the novel combination of checkpoint inhibitors, lenvatinib, and local therapy, noting the great improvement in progression-free survival, however, the grade 3 and grade 4 toxicities were a concern.

“I would probably be very cautious in using this and selecting the right patient, especially to get the meaningful benefit,” he said.

From a global perspective, including a low- and middle-income country like India where TACE is very widely used, “I would definitely say this is a very practice-changing study,” he added.

Patient Subgroups?

“Do we need to subject every embolization-eligible patient to TACE plus immunotherapy?” Chan asked. He suggested future studies are warranted to identify subgroups who would benefit the most based on factors like tumor burden or organ function.

Chan questioned the additional price to pay for improvements in progression-free survival when combining checkpoint inhibitors with TACE. “Generally, all these five studies [looking at this treatment] show that the combination is associated with higher grade adverse events,” he said.

“I’m not saying that we shouldn’t prescribe this regimen to our patients because of higher adverse events, because in oncology world, we know that we need trade-off when we combine treatment, but what bothers me a little bit is when you look at the adverse events leading to discontinuation of either drug or both drugs,” he said.

“I think we need quality of life data to see how patients feel about this combination, and, unfortunately, at this moment, we have not seen any quality-of-life data coming from these studies,” Chan added.

The full EMERALD-3 manuscript has been accepted for publication by Lancet Oncology.

The study was funded by AstraZeneca. Abou-Alfa disclosed being a consultant or advisor for AstraZeneca and many other pharmaceutical companies and that his financial institution receiving funding from AstraZeneca and others.Chan disclosed that he or his institution receiving honoraria from AstraZeneca, among others, and that he being a consultant or advisor to AstraZeneca and others. Sathyanarayan disclosed being employed by OncoMinds, Inc., and receiving honoraria from AstraZeneca and others.

Damian McNamara is a freelance contributor to Medscape Medical News. He worked full-time for Medscape and WebMD from 2018 to 2024. Damian has a BA in chemistry and an MA in science, health and environmental reporting/journalism.