Results of the phase III EMERALD-3 trial showed that combining transarterial chemoembolization (TACE) with the immunotherapy-based STRIDE regimen, (single tremelimumab[an anti-cytotoxic T lymphocyte–associated antigen 4] plus regular interval durvalumab [anti–PD-L1]) with or without lenvatinib (oral multikinase VEGF and FGF inhibitor), slowed disease progression and prolonged survival in patients with embolization-eligible, unresectable hepatocellular carcinoma. The findings were presented at the 2026 ASCO Annual Meeting by Ghassan K. Abou-Alfa, MD, JD, MBA, PhD (hc), FASCO, of Memorial Sloan Kettering Cancer Center, Weill Medical College at Cornell University, New York, USA, and Trinity College Dublin, Dublin, Ireland.
Ghassan K. Abou-Alfa, MD, JD, MBA, PhD (hc), FASCO
“EMERALD-3 is the first phase III study to demonstrate that a STRIDE-based regimen improves clinical outcomes when combined with TACE, supporting its role as a potential new treatment option in unresectable, embolization-eligible hepatocellular carcinoma,” Dr. Abou-Alfa said. He added that the findings suggest STRIDE is the “driver of efficacy in the intent-to-treat population.”
At a press briefing, ASCO Expert Vishwanath Sathyanarayanan, MD, DM, Lead, Oncosciences, Karnataka Region, Apollo Hospitals, Bangalore, India, said the improvement in progression-free survival with STRIDE plus TACE makes the regimen a “compelling option” for this patient population. “These findings are likely to influence clinical practice and may be considered practice-changing for medical oncologists treating hepatocellular carcinoma globally,” Dr. Sathyanarayanan said.
Dr. Abou-Alfa provided some background: “In the embolization-eligible setting for hepatocellular carcinoma, TACE has been the global standard of care for more than two decades. However, outcomes remain poor, with a median progression-free survival of 8 to 10 months. Repeated TACE procedures become less effective over time and may further compromise liver function. Currently, no systemic therapy-based options are approved globally for these patients.”
Vishwanath Sathyanarayanan, MD, DM
The global phase III EMERALD-3 trial evaluated whether combining STRIDE—an approved front-line regimen that has demonstrated a sustained overall survival benefit—with TACE, with or without oral lenvatinib, could delay disease progression in this patient population. As Dr. Abou-Alfa explained, combining TACE with immunotherapy and antiangiogenic therapies may enhance antitumor activity. “When we apply TACE, we are releasing neoantigens, which up-regulate immune checkpoints. This gives us an opportunity to apply a checkpoint inhibitor, in this case durvalumab, and also to address T-cell infiltration and blood vessels with the anti-VEGF [vascular endothelial growth factor receptor] agent lenvatinib. Controlling all this at the top of the chain of command is the anti-CTLA4 agent tremelimumab,” he said.
Dr. Abou-Alfa presented the prespecified final analysis of the primary endpoint, progression-free survival, comparing TACE plus STRIDE and lenvatinib with TACE alone. He also reported other efficacy outcomes including PFS of TACE plus STRIDE compared with TACE alone, and the overall survival. He noted that these comparisons were descriptive only pending data maturity. Formal statistical analyses of these endpoints will be conducted once the prespecified conditions of the hierarchical testing strategy have been met.
Key Findings in EMERALD-3
EMERALD-3 enrolled 760 adults, most of whom were male (83.2%) and Asian (72.1%). Participants were randomly assigned to receive STRIDE plus lenvatinib with TACE (Arm A), STRIDE with TACE (Arm B), or TACE alone (Arm C).
In the primary endpoint analysis of the intent-to-treat population (64% data maturity), median progression-free survival was 13.0 months with STRIDE, lenvatinib, and TACE vs 9.8 months with TACE alone (hazard ratio [HR] = 0.70; P = .0007). The 2-year progression-free survival rate was 30.4% vs 19.3%, respectively, Dr. Abou-Alfa reported.
Among the first 175 participants (75% data maturity), STRIDE plus TACE (without lenvatinib) also improved progression-free survival compared with TACE alone. Median progression-free survival was 12.9 vs 8.1 months (HR = 0.71; P = .0062), and the 2-year progression-free survival rate was 30.0% vs 20.3%, respectively.
Median overall survival at 40% maturity was 39.5 months with STRIDE, lenvatinib, and TACE vs 34.7 months with TACE alone (HR = 0.84; P = .1814). The 2-year overall survival rate was 66.9% vs 61.5%, respectively.
In the same comparison, median overall survival was not calculable with STRIDE plus TACE and was 32.9 months with TACE alone (HR = 0.70; P = .0233). The 2-year overall survival rate was 68.0% vs 57.8%, respectively. Under the study’s hierarchical statistical testing strategy, these efficacy comparisons were considered descriptive only.
“The overall survival is only at 40% maturity; nonetheless, there is a trend toward improved outcomes with STRIDE plus lenvatinib and TACE,” Dr. Abou-Alfa noted. “However, we observed a similar trend with STRIDE plus TACE with maturity at 45%.”
Objective response rates were 38.9% in Arm A, 40.8% in Arm B, and 27.0% in Arm C. Patients in the TACE-only arm were the most likely to undergo at least three TACE procedures (40.7% vs 22.0% in Arm A and 33.7% in Arm B).
Grade 3 or 4 adverse events were more common among patients who received STRIDE plus TACE, with or without lenvatinib, than among those treated with TACE alone. Such events occurred in 62.7% of patients receiving the triplet regimen, 48.6% receiving STRIDE plus TACE, and 18.6% receiving TACE alone. Treatment interruptions of the systemic therapies occurred in 84.0% of patients receiving the triplet regimen and 44% of those receiving STRIDE plus TACE (not relevant to TACE alone). The most common adverse events in each group were consistent with the known safety profiles of the respective treatments.
Does Lenvatinib Add Benefit?
Whether lenvatinib adds benefit to STRIDE plus TACE remains unanswered, as the trial was not designed to formally compare Arm A with Arm B. Nevertheless, the findings have generated interest in this question. Median progression-free survival was 13.0 months with STRIDE plus lenvatinib and TACE (HR = 0.70) and 12.9 months with STRIDE plus TACE alone (HR = 0.71), although these results should not be interpreted as a direct comparison between the two treatment arms.
“A formal comparison of these arms was not planned. We did a preplanned subgroup analysis but it was not part of the statistical hierarchical methodology, and in that analysis we saw that the use of lenvatinib really did not suggest an added contribution, except perhaps in patients with nonviral histology (HR = 0.70),” Dr. Abou-Alfa said. He noted that this analysis was based on a very small subset of patients, most of whom were from Japan, and therefore should be interpreted with caution.
“Do we need lenvatinib? It seems not,” Dr. Abou-Alfa told journalists at a press briefing. “It seems we will be okay to give STRIDE plus TACE without lenvatinib, especially considering the toxicity that lenvatinib can add.”
Dr. Abou-Alfa acknowledgedthe growing interest in combining transarterial radioembolization (TARE) with immunotherapy regimens and noted that studies evaluating this approach are ongoing. The full EMERALD-3 manuscript has been accepted for publication in Lancet Oncology.
DISCLOSURE: Dr. Abou-Alfa discloses institutional research support from AbbVie, Agenus, Amgen, Arcus, AstraZeneca, Atara, BeiGene, BioNTech, BMS, Coherus, Digestive Care, Elicio, Genentech/Roche, Helsinn, Incyte, J-Pharma, Revolution Medicines, Tango Therapeutics, Yiviva, and consulting support from AbbVie, Ability Pharma, Agenus, Alligator Biosciences, Amgen, Astellas, Arcus, AstraZeneca, Autem, Berry Genomics, BioNTech, BMS, Boehringer Ingelheim, FibroGen, Genentech/Roche, ImageneBio, Immuneering, Ipsen, J-Pharma, Merck, Merus, MOMA Therapeutics, Neogene, Novartis, Pfizer, Regeneron, Revolution Medicines, Servier, Syros, Tango Therapeutics, Tempus, Vector, and Yiviva. Dr.Sathyanarayanan has served in a leadership role with Oncominds, Inc.; owned stock in Oncominds, Inc.; has received honoraria from Alkem Laboratories, AstraZeneca, Glenmark, Intas, Lupin Pharmaceuticals, MSD Oncology, NATCO Pharma, Novartis, Reddy Labs, Takeda and Zydus Pharmaceuticals; and has served as a consultant or advisor for Zydus Pharmaceuticals.
REFERENCE
1. Abou-Alfa GK, Ren Z, Erinjeri JP, et al: Efficacy and safety results from EMERALD-3: A phase 3, randomized study of tremelimumab plus durvalumab with or without lenvatinib combined with transarterial chemoembolization (TACE) in participants with unresectable embolization-eligible hepatocellular carcinoma. 2026 ASCO Annual Meeting. Abstract LBA4000. Presented June 1, 2026.
EXPERT POINT OF VIEW
EMERALD-3’s invited discussant, Stephen L. Chan, MD, Professor in the Department of Clinical Oncology at The Chinese University of Hong Kong, lauded the improvement in progression-free survival with TACE plus STRIDE but questioned whether the combination, with or without lenvatinib, is ready for routine clinical use.
Stephen L. Chan, MD
Dr. Chan noted that EMERALD-3 strengthens the findings of four previous studies showing that the addition of immunotherapy to TACE improves progression-free survival, including one presented at the 2026 ASCO Annual Meeting evaluating camrelizumab (PD-1 immune checkpoint inhibitor) plus rivoceranib (oral VEGFR2 tyrosine kinase inhibitor).2 The consistency of the hazard ratios across these studies, which ranged from approximately 0.60 to 0.70, suggests a possible class effect, he said. [Editor’s note: Camrelizumab and rivoceranib are made in China; the U.S. Food and Drug Administration accepted the resubmitted new drug application for camrelizumab plus rivoceranib as first-line treatment for unresectable hepatocellular carcinoma and set a PDUFA action date of July 23, 2026.]
“But I think it makes sense to ask whether the triplet will further optimize the outcome of patients,” he said. “In the exploratory analysis, the shape of the progression-free survival curve is not substantially different; therefore, I question the contribution of lenvatinib to STRIDE. Considering the toxicity associated with STRIDE plus lenvatinib, it makes more sense not to give lenvatinib initially but to consider it as a subsequent treatment.”
Commenting on overall survival, Dr. Chan noted the complexity of the treatment sequence and its potential to confound interpretation. The first 6 months represent “a TACE phase,” in which TACE is combined with systemic immunotherapy (STRIDE), followed by a phase in which immunotherapy is combined with targeted therapy (lenvatinib). After that, “in the real world,” some patients may receive a variety of subsequent therapies. “Therefore, when you look at the overall survival curves, it’s a good sign that with such a short follow-up we already see a trend toward separation of the overall survival curves, but we need to be cautious and let the metrics mature,” he said.
Dr. Chan also observed that in EMERALD-3 and the other trials evaluating TACE plus immunotherapy, the overall survival curves overlap during the first 6 to 9 months, corresponding to the TACE phase. This raises questions about the source of any eventual survival benefit—whether it is driven by the TACE plus systemic therapy phase, the systemic therapy maintenance phase, or subsequent treatment. More detailed information is needed on subsequent treatment, he said.
Dr. Chan emphasized that a key question is whether every embolization-eligible patient should receive TACE plus immunotherapy. “What is the additional price to pay for the improvement in progression-free survival achieved with these combinations?” he asked.
“You see the rates of grade 3 and all-cause serious adverse events are higher... In the oncology world, we know we need tradeoffs when we combine treatments, but overall in these studies about 20% of patients need to discontinue any drug, and with the triplet [that includes lenvatinib] it is more than 35%. Is this a worthwhile price to pay?” he asked.
“We need quality of life data to see how patients feel about this combination, and unfortunately, at this moment, we have not seen any,” Dr. Chan said. “I would like to urge the investigators to report this for TACE combined with systemic therapy. This will help us make decisions.”
Future studies are needed to identify the subgroups most likely to benefit from combination therapy based on factors such as tumor burden or organ function. “I don’t think we need to subject every single embolization-eligible patient to TACE plus STRIDE therapy,” Dr. Chan concluded.
DISCLOSURE: Dr. Chan had personal financial disclosures for AstraZeneca, Eisai, Elevar Therapeutics, Ipsen, Exelixis, MSD Oncology, and Roche.
REFERENCES
1. Abou-Alfa GK, Ren Z, Erinjeri JP, et al: Efficacy and safety results from EMERALD-3: a phase 3, randomized study of tremelimumab plus durvalumab with or without lenvatinib combined with transarterial chemoembolization (TACE) in participants with unresectable embolization-eligible hepatocellular carcinoma. 2026 ASCO Annual Meeting. Abstract LBA4000. Presented June 1, 2026.
2. Jia W-D, Qin S, Zhou J, et al: Camrelizumab plus rivoceranib with transarterial chemoembolization (TACE) vs TACE alone in unresectable hepatocellular carcinoma: A randomized, phase 3 trial. 2026 ASCO Annual Meeting. Abstract 4001. Presented June 1, 2026.
