HK study: START-FIT strategy using STRIDE regimen promising in HCC

Sequential transarterial chemoembolization, stereotactic body radiotherapy, and immunotherapy (START-FIT) using the STRIDE regimen of single-dose tremelimumab plus regular-interval durvalumab offers promising efficacy and is well tolerated in patients with locally advanced, unresectable hepatocellular carcinoma (HCC), a single-arm, multicentre, phase II study in Hong Kong has shown.

“START-FIT using anti–PD-L1 therapy has demonstrated promising efficacy in locally advanced HCC,” wrote the researchers from the University of Hong Kong, Chinese University of Hong Kong, Tuen Mun Hospital, Queen Elizabeth Hospital, and Gleneagles Hospital Hong Kong. [Lancet Gastroenterol Hepatol 2023;8:169-178; JAMA Oncol 2024;10:1548-1553] “However, there is limited prospective data on the combination of locoregional therapy with anti–PD-L1 and anti–CTLA-4 therapies.”

They therefore evaluated the activity of the START-FIT strategy using the STRIDE regimen in 33 adult patients with unresectable HCC (≥5 cm, ≤3 nodules, Child-Pugh class A–B7) (median age, 67 years; male, 91 percent) recruited between 2020 and 2024. [Chiang CL, et al, ASCO GI 2026, abstract 540]

Hepatitis B was the predominant HCC aetiology (78.7 percent) among the study’s participants. The median tumour size was 11 cm. Macrovascular invasion was present in 72.7 percent of the patients (hepatic vein invasion, n=14; branched portal vein invasion, n=5; both, n=5). Barcelona Clinic Liver Cancer (BCLC) staging was A–B in 27 percent and C in 73 percent.

The patients received a single episode of transarterial chemoembolization (TACE), followed 4 weeks later by stereotactic body radiotherapy (SBRT; 27.5–40 Gy in 5 fractions). The STRIDE regimen was started 1 week after completion of SBRT, with single-dose tremelimumab (300 mg) plus durvalumab (1,500 mg) followed by regular-interval durvalumab (1,500 mg) Q4W.

The primary endpoint of objective response rate by modified RECIST 1.1 criteria was 72.7 percent (n=24/33). Complete response (CR) was achieved in 42.4 percent (n=14/33) of patients, while partial response (PR) was achieved in 27.3 percent (n=9/33). About 9 percent of patients (n=3/33) had stable disease, while 12.1 percent (n=4/33) had progressive disease.

Among patients with CR, seven were converted to receive curative treatment (resection; n=3; ablation, n=4), while 14 were under surveillance. Among patients with PR, six underwent curative surgery.

At 18 months, local control rate was 96.6 percent, progression-free survival rate was 61.8 percent, and overall survival rate was 90.0 percent.

Grade ≥3 treatment-related adverse events were reported in 36.3 percent (n=13/33) of patients. Most of these events were transient aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevations after TACE (n=5). Grade ≥3 immune-related adverse events were reported in 12.1 percent (n=4/33) of patients.

“START-FIT using the STRIDE regimen is a safe and promising therapy in locally advanced HCC,” the researchers concluded.