Sintilimab, an anti–PD-1 antibody, in combination with a bevacizumab biosimilar as first-line therapy significantly improved survival compared to sorafenib in patients with advanced hepatocellular carcinoma, according to findings presented by Ren et al at the ESMO Asia Virtual Congress 2020 (Abstract LBA2).

ORIENT-32

Researchers presented data from the phase III efficacy portion of the randomized, open-label, multicenter phase II/III ORIENT-32 study, which evaluated sintilimab plus a bevacizumab biosimilar vs sorafenib as first-line treatment for advanced hepatocellular carcinoma. The phase II portion of the study demonstrated acceptable safety with the combination.

ORIENT-32 enrolled patients with unresectable or metastatic hepatocellular carcinoma naive to systemic hepatocellular carcinoma treatment. In phase III, following 2:1 random assignment, 380 patients were treated with intravenous sintilimab at 200 mg every 3 weeks plus a bevacizumab biosimilar at 15 mg/kg given intravenously every 3 weeks; 191 patients were treated with oral sorafenib at 400 mg twice daily. Stratification factors included macrovascular invasion and/or extrahepatic metastasis (presence vs absence), baseline alpha fetoprotein level (< 400 vs ≥ 400 ng/mL) and Eastern Cooperative Oncology Group performance status (0 vs 1).

The primary endpoints were overall survival and progression-free survival by independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Among the patients enrolled by data cut-off on 15 August 2020, the baseline characteristics were well-balanced; the majority (94.2%) of patients had hepatitis B infection and 4.2% of patients had Child-Pugh B status of chronic liver disease.

Results

With median follow-up of 10 months, median overall survival was significantly longer with the sintilimab plus the bevacizumab biosimilar than with sorafenib, and the combination demonstrated a 43.1% decreased risk of all-cause death; median overall survival was not estimable compared to 10.4 months, respectively (hazard ratio [HR] = 0.569, 95% confidence interval [CI] = 0.431–0.751, P < .0001).

Similarly, improved progression-free survival was also demonstrated, with a 43.5% decreased risk of progression assessed by IRRC per RECIST version 1.1; median progression-free survival with the combination was 4.6 months compared to 2.8 months with sorafenib (HR = 0.565, 95% CI = 0.455–0.701, P < .0001).

Overall benefit favored the combination over sorafenib consistently across all the subgroups evaluated.

Efficacy-evaluable patients demonstrated a confirmed objective response rate of 20.5% (95% CI = 16.5–25.1) with the combination vs 4.1% (95% CI = 1.7–8.2) with sorafenib.

Among patients receiving at least one drug dose, any-grade treatment-related adverse events occurred in 88.7% of patients receiving the combination vs 93.5% of sorafenib-treated patients. Grade 3/4 treatment-related adverse events were reported in 33.7% and 35.7% of patients, respectively.

According to the authors, sintilimab plus a bevacizumab biosimilar showed significant improvements in clinical benefits compared to sorafenib as first-line treatment of patients with advanced hepatocellular carcinoma.

Disclosure: Funding for this study was reported from Innovent Biologics, Inc. For full disclosures of the study authors, visit oncologypro.esmo.org.