Frontline sintilimab + bevacizumab biosimilar ups survival in advanced HCC

Combining the anti-PD-1 antibody sintilimab and a bevacizumab biosimilar significantly improves survival compared with the standard treatment of sorafenib in the first-line setting for patients with advanced, unresectable hepatocellular carcinoma (HCC), according to the ORIENT-32 study presented at ESMO Asia 2020.

Previously, the phase II part of the ORIENT-32 study has also shown acceptable safety profile with the combination regimen of sintilimab plus a bevacizumab biosimilar.

The current phase III part of the open-label, multicentre study involved 571 patients (~88.5 percent male) with unresectable or metastatic HCC, who did not have prior systemic treatment. They were randomized 2:1 in a ratio to receive intravenous sintilimab 200 mg Q3W plus a bevacizumab biosimilar (Sinbev arm) at 15 mg/kg Q3W or oral sorafenib 400 mg BID. Majority of the patients (94.2 percent) had hepatitis B infection and 4.2 percent were with Child-Pugh B status. [ESMO Asia, abstract LBA2]

After a median follow-up of 10.0 months, patients treated with the combination therapy had significantly prolonged overall survival (OS) than the sorafenib arm (median, not estimable vs 10.4 months; hazard ratio [HR], 0.569; p<0.0001).

Similarly, the coprimary endpoint of progression-free survival (PFS) was significantly improved in the Sinbev arm vs the sorafenib arm (median, 4.6 vs 2.8 months; HR, 0.565; p<0.0001), as assessed by an independent radiographic review committee (IRRC) based on RECIST v1.1.

In addition, the survival benefits with Sinbev were consistent across subgroups regardless of the presence of microvascular invasion, ECOG performance status, Child-Pugh class, and BCLC staging.

The objective response rates, as per RECIST v1.1 by the IRRC, were also higher in the Sinbev arm vs the sorafenib arm (20.5 percent vs 4.1 percent; p<0.0001), among patients with evaluable baseline tumour assessment.

“ORIENT-32 is the first randomized phase III study reporting the efficacy and safety of [an] anti-PD-1 antibody plus bevacizumab biosimilar vs sorafenib as first-line treatment in patients with advanced unresectable HCC with a large proportion of HBV infection,” said lead author Dr Ren Zhenggang from Zhongshan Hospital, Fudan University in Shanghai, China.

The findings are in line with those of the IMbrave 150 study, which found that combining the anti-PD-L1 antibody atezolizumab plus bevacizumab conferred significant survival benefit vs sorafenib in patients with unresectable HCC.

Sintilimab has recently been approved in China for classical Hodgkin's lymphoma that is refractory or has relapsed following at least two lines of systemic chemotherapy.

“The combination regimen had an acceptable safety profile without new unexpected safety signals,” noted Ren.

The rates of treatment-related adverse events (TRAEs) of any grade were 88.7 percent in the Sinbev combination therapy arm compared with 93.5 percent in the sorafenib arm. Grade 3/4 TRAEs occurred at a rate of 33.7 percent and 35.7 percent, respectively.

“Incidence of patients testing ADA-positive was very low, suggesting a potentially higher clinical benefit with this combination setting,” said Ren. Among the 363 patients who were evaluable for adenosine deaminase (ADA), only 3.3 percent tested positive for treatment-emergent ADA of sintilimab.

“Sintilimab + bevacizumab biosimilar could be a candidate first-line treatment option for patients with unresectable or metastatic HCC,” he suggested.

*BCLC: Barcelona Clinic Liver Cancer