Nivolumab after selective internal radiation therapy for the treatment of hepatocellular carcinoma: a phase 2, single-arm study

Abstract

PurposeTo evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in combination with a PD-1 inhibitor in patients with unresectable hepatocellular carcinoma (uHCC) and liver-only disease ineligible for chemoembolization.Patients and methodsNASIR-HCC is a single-arm, multicenter, open-label, phase 2 trial that recruited from 2017 to 2019 patients who were naïve to immunotherapy and had tumors in the BCLC B2 substage (single or multiple tumors beyond the up-to-7 rule), or unilobar tumors with segmental or lobar portal vein invasion (PVI); no extrahepatic spread; and preserved liver function. Patients received SIRT followed 3 weeks later by nivolumab (240 mg every 2 weeks) for up to 24 doses or until disease progression or unacceptable toxicity. Safety was the primary endpoint. Secondary objectives included objective response rate (ORR), time to progression (TTP), and overall survival (OS).Results42 patients received SIRT (31 BCLC-B2, 11 with PVI) and were followed for a median of 22.2 months. 27 patients discontinued and 1 never received Nivolumab. 41 patients had any-grade adverse events (AE) and 21 had serious AEs (SAE). Treatment-related AEs and SAEs grade 3–4 occurred in 8 and 5 patients, respectively. Using RECIST 1.1 criteria, ORR reported by investigators was 41.5% (95% CI 26.3% to 57.9%). Four patients were downstaged to partial hepatectomy. Median TTP was 8.8 months (95% CI 7.0 to 10.5) and median OS was 20.9 months (95% CI 17.7 to 24.1).ConclusionsThe combination of SIRT and nivolumab has shown an acceptable safety profile and signs of antitumor activity in the treatment of patients with uHCC that were fit for SIRT.Trial registration numberNCT03380130

Optimization of the Clinical Effectiveness of Radioembolization in Hepatocellular Carcinoma with Dosimetry and Patient-Selection Criteria

“…Controlled trials currently investigate the combination of SIRT plus immunotherapy in patients with intermediate and advanced stages of HCC. Preliminary results of the combination of nivolumab three weeks after SIRT demonstrated a favorable tolerability and encouraging response rates [24,25]. A randomized trial (NCT04541173) is also investigating the safety and effectiveness of SIRT followed by the combination of atezolizumab plus bevacizumab.…”

Selective Internal Radiation Therapy Approval for Early HCC: What Comes Next?

“…(5) Preliminary data suggest enhanced activity of this combination. (6) The long-term safety of SIRT is also an important issue. With seven systemic agents and two combinations approved by the FDA to treat HCC, survival beyond 3 years can be reached by a significant proportion of patients in the advanced stage.…”

Nifuroxazide Suppresses PD-L1 Expression and Enhances the Efficacy of Radiotherapy in Hepatocellular Carcinoma

“…This finding could potentially provide a valuable strategy for patients who exhibit resistance to radiation therapy in clinical practice. Moreover, clinical trial investigations have demonstrated that nivolumab, a PD-1 monoclonal antibody, when combined with radiotherapy for HCC, exhibits promising safety and efficacy (26). This evidence supports the future application of nifuroxazide in the treatment of HCC.…”