In a single-arm study, 100% of patients treated with sintilimab plus stereotactic body radiotherapy who had oligometastases of hepatocellular carcinoma achieved disease control and were alive and progression free at 6 months.
All patients treated with sintilimab plus stereotactic body radiotherapy (SBRT) who had oligometastases of hepatocellular carcinoma (HCC) achieved disease control and were alive and progression free at 6 months, according to a preliminary analysis of a single-arm study (NCT03857815).
Yi-Xing Chen, MD, PhD, of Zhongshan Hospital, Fudan University in Shanghai, China, said in a presentation during the 2021 Digital Liver Cancer Summit that the combination of SBRT and sintilimab showed encouraging antitumor activity in patients with oligometastatic HCC.
SBRT is an emerging option for the treatment of oligometastatic tumors. In oligometastatic HCC, the radiation approach has induced local control with low toxicity, yet distant progression is still a cause of treatment failure, especially in patients with recurrent disease.
In the ongoing phase 2 study, investigators are exploring the synergistic effect of radiation and immunotherapy with the investigational PD-1 inhibitor sintilimab in combination with SBRT in patients with oligometastases of HCC. The ongoing trial is seeking to enroll 30 patients with unresectable HCC who have a maximum of 5 recurrent or metastatic lesions, Child-Pugh A disease, and an ECOG performance status of 0 or 1.
Patients received 200 mg intravenous sintilimab every 3 weeks plus SBRT to all lesions starting on day 1 of cycle 1. Treatment was continued for up to a year or until progression or unacceptable toxicity.
Progression-free survival (PFS) by modified RECIST criteria is the primary end point. Secondary end points include objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety and tolerability.
Twenty patients had been enrolled as of the data cutoff date for the preliminary analysis of the trial. The median age was 64.5 years (range, 33-77), 95% of patients were male, and 85% had an ECOG performance status of 0. Ninety-five percent had hepatitis B virus and 85% had intrahepatic recurrence. Prior therapy included surgery for 85%, ablation for 45%, and transarterial chemoembolization for 65%. Seventy percent of patients had 1 lesion, 25% had 2 lesions, and 5% had 3.
The median follow-up was 7.5 months (range, 1.2-20.1). SBRT administration was a median of 54 Gy (range, 48-60) and 6 fractions (range, 6-10), and sintilimab treatment duration was a median of 6.1 months (range, 0.7-12.7). At the time of data cutoff, 60% of patients remained on treatment; 10% discontinued at the end of the year. Ten percent of patients discontinued due to progression, 10% due to treatment-related adverse events (AEs), 5% due to unrelated AEs, and 5% due to withdrawal of consent.
Sixteen patients were evaluable for response; among these patients, investigators observed objective responses in 15, for an ORR of 93.8%, and the remaining patient reached stable disease, for a DCR of 100%. At 1 year, the local control rate was 100%.
The median duration of response, median PFS, and OS were not reached at the time of data cutoff. At 6 months the PFS rate was 100% and at 12 months it was 71.4%.
Investigators observed any-grade treatment-related AEs in 40% of all treated patients, only 1 of which was grade 3/4. They reported serious AEs in 15% of patients, which were treatment related in 2 of the 3 patients. No fatal events were reported. According to Chen, no unexpected toxicities have been observed thus far in the study.
Treatment-related AEs consisted of platelet count decrease in 15% of patients; creatine kinase increase in 15%, which was grade 3 for 1 patient; rash in 10%; alanine/aspartate aminotransferase increase in 10%; dry eyes in 5%; and myocarditis in 5%.
Chen concluded that longer follow-up is necessary to confirm the results from the preliminary analysis.
Chen YX, Yang P, Du SS, et al. A phase II study of stereotactic body radiotherapy (SBRT) combined with sintilimab in patients with oligometastases of hepatocellular carcinoma (HCC). Abstract presented at: European Association for the Study of the Liver Digital Liver Cancer Summit 2021; February 5-6, 2021; Virtual. Abstract O04.