STRIDE-Based Regimens Plus TACE Improve PFS in Embolization-Eligible HCC

For more than two decades, transarterial chemoembolization (TACE) has served as the global standard of care for patients with unresectable, embolization-eligible hepatocellular carcinoma (eeHCC). However, results from the Phase 3 EMERALD-3 trial, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, indicate a potential paradigm shift.

The study demonstrated that combining TACE with the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab) significantly improves progression-free survival (PFS) compared to TACE alone.

Ghassan K. Abou-Alfa, MD, JD, MBA, PhD, of Memorial Sloan Kettering Cancer Center, presented the findings, which suggest that the addition of immunotherapy — and in some cases, a tyrosine kinase inhibitor (TKI) — to local therapy may overcome the historical limitations of TACE monotherapy, which typically yields a median PFS of only 8 to 10 months.

The synergy of local and systemic therapy

The rationale behind EMERALD-3 rests on the immunity cycle. TACE induces tumor cell death, which triggers the release of tumor antigens and upregulates immune checkpoints. By introducing durvalumab (Imfinzi, anti-PD-L1) and tremelimumab (Imjudo, anti-CTLA4) into this environment, investigators sought to enhance T-cell priming and infiltration. The addition of lenvatinib (Lenvima), a VEGF-targeting TKI, further addresses the anti-angiogenic needs of these vascular tumors.

EMERALD-3 study design

The global, randomized, open-label study enrolled 760 participants with pathologically or radiologically confirmed HCC not amenable to curative treatment. Patients were randomized into three arms:

• Arm A: STRIDE plus lenvatinib and TACE (n=293)
• Arm B: STRIDE plus TACE (n=175)
• Arm C: TACE monotherapy (n=292)

The primary endpoint was PFS for Arm A versus Arm C. Key secondary endpoints included overall survival (OS) and the performance of Arm B versus Arm C.

PFS and OS results

The study met its primary endpoint, showing a statistically significant improvement in PFS for the triplet combination. Patients in Arm A (STRIDE+L+TACE) achieved a median PFS of 13.0 months, compared to 9.8 months in the TACE-only arm (HR 0.70; p=0.0007). The 12-month PFS rate was 56.2% for the triplet compared to 42.9% for TACE alone.

Arm B (STRIDE+TACE) also showed clinically meaningful improvements, with a median PFS of 12.9 months versus 8.1 months for the first 175 participants in the TACE arm (HR 0.71).

Abou-Alfa noted that these results suggest STRIDE is a major driver of efficacy in this population.

While the OS data are still maturing, interim analysis showed a favorable trend for the combination. In Arm A, the median OS was 39.5 months versus 34.7 months for Arm C (HR 0.84). Notably, significantly fewer patients in the combination arms required subsequent anticancer therapy compared to the TACE monotherapy arm (43.3% in Arm A vs. 70.2% in Arm C), likely due to the prolonged initial response.

Nursing implications: Navigating a complex safety profile

For oncology nurses, the transition from TACE monotherapy to these intensive combinations requires heightened vigilance. The safety profile was "acceptable and consistent" with the known profiles of the individual agents, but the combination arms experienced significantly higher rates of adverse events (AEs).

Key safety data included:

• Any Grade AEs: Reported in 99.7% of patients in Arm A and 98.9% in Arm B, compared to 88.3% for TACE alone.
• Grade 3/4 AEs: These occurred in 71.4% of the triplet arm (Arm A) and 64.0% of the STRIDE+TACE arm (Arm B), significantly higher than the 28.6% seen with TACE alone.
• Management of Lenvatinib: In Arm A, 78.7% of patients required a lenvatinib interruption, and 49.5% required a dose reduction.

Nurses play a critical role in educating patients that while these regimens are more effective, they are also more demanding. Proactive monitoring for immunotherapy-related AEs (irAEs) from durvalumab and tremelimumab, as well as TKI-associated toxicities from lenvatinib, is essential to keep patients on therapy. The investigators noted that a significant portion of AEs (67.6% to 77.1%) were assessed as being "provoked by TACE," emphasizing the need for meticulous post-procedural care.

Conclusion

EMERALD-3 is the first Phase 3 study to demonstrate that a STRIDE-based regimen improves clinical outcomes when combined with TACE. As this combination moves toward becoming a potential new treatment option in eeHCC, oncology nurses will be at the forefront of managing these complex patients, balancing the gains in progression-free survival with the intensified monitoring required for multi-agent therapy.

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 (pts) with unresectable embolization-eligible hepatocellular carcinoma (eeHCC). Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract LBA4000.