Treatment with the PD-1 inhibitor nivolumab demonstrated an objective response rate of 9% as a second-line therapy for patients with hepatocellular carcinoma.
In previous findings from the study, the ORR was 19%; however, for the latest update, the investigators cautioned that data were preliminary and so they may have underestimated the response rate. In the study, responses were frequently delayed, with a complete response occurring after 24 months of treatment. When considering those with stable disease, the disease control rate was 65%.
“The updated nivolumab in HCC data are still very encouraging. The disease control rate was 65%, and there were 3 complete responses,” said Kabir Mody, MD, from the Mayo Clinic.
The phase I/II study explored ascending doses of nivolumab ranging from 0.1 mg/kg to 10 mg/kg every 2 weeks for up to 2 years. All patients enrolled had Child-Pugh class A disease. The primary endpoint was ORR by RECIST criteria. Secondary outcome measures focused on overall survival (OS), progression-free survival, and biomarker assessments.
In an expansion cohort, nivolumab was administered at 3 mg/kg across 4 groups, including those uninfected by hepatitis who were sorafenib naïve/intolerant, those uninfected following progression on sorafenib, those with hepatitis C virus (HCV) infection, and those with hepatitis B virus (HBV) infection.
Overall, 206 patients were enrolled in the study, 65% with extrahepatic metastasis and 7% with vascular invasion. Most patients had received prior sorafenib (64%).
Of enrolled patients, 91 had ≥18 weeks of follow-up and were evaluable for response. For those who responded to treatment, the median duration of response was 17 months (range, 6-24). Stable responses occurred as late as 12 to 18 months following the initiation of treatment. Overall, PD-L1 status did not appear to impact response rates. The 6-month OS rate was 69% (95% CI, 0.43-0.85).
For uninfected, sorafenib-naïve or intolerant patients (n = 22), the ORR was 14%. In those who progressed on prior sorafenib and were uninfected (n = 27), the ORR was 7%. In the HCV-infected (n = 21) and HBV-infected (n = 21) patients, the ORRs were 14% and 0%, respectively.
Across all cohorts of the trial, patients received 5 to 6 doses of nivolumab (range, 1-19). Half of patients experienced a treatment-related adverse event (AE), with the most frequent events being fatigue (17%) and pruritus (12%). Grade 3/4 treatment-related AEs were seen in 14% of patients, with the most common being ALT and AST increases (3% each).
In the frontline setting, nivolumab is being compared with sorafenib for patients with HCC in a phase III study. The primary endpoints are time to progression and OS. The study hopes to enroll 726 patients with an estimated completion date of July 2017 (NCT02576509).