Sorafenib ( Nexavar ) is approved as first-line therapy for patients with advanced hepatocellular carcinoma ( HCC ), but there is still an unmet need to prolong survival and improve tolerability.
A phase III study compared clinical efficacy and safety of Nivolumab with Sorafenib as first-line therapy in patients with advanced hepatocellular carcinoma.
Systemic therapy–naive patients aged greater than or equal to 18 years with advanced hepatocellular carcinoma were randomized 1:1 to Nivolumab ( 240 mg IV Q2W ) or Sorafenib ( 400 mg oral BID ).
Primary endpoint was overall survival ( OS ). Additional endpoints were objective response rate ( ORR ) and progression-free survival ( PFS ) by blinded independent central review per RECIST v1.1, efficacy by tumor programmed death ligand 1 ( PD-L1 ) expression, and safety.
743 patients with advanced hepatocellular carcinoma were randomized to Nivolumab ( n = 371 ) or Sorafenib ( n = 372 ) with minimum follow-up of 22.8 months at data cutoff.
Overall survival did not meet the predefined threshold of statistical significance ( hazard ratio, HR=0.84, P = 0.0419 ).
Median overall survival ( mOS ) was 16.4 months for Nivolumab and 14.7 months for Sorafenib ( HR=0.85 [ 95% CI: 0.72–1.02 ]; P = 0.0752 ).
Clinical benefit was observed across predefined subgroups, including hepatitis infection status, presence of vascular invasion and/or extrahepatic spread, and region ( Asia vs non-Asia ).
ORR was 15% for Nivolumab ( 14 patients with complete response [ CR ] ) and 7% for Sorafenib ( 5 patients with CR ).
Grade 3/4 treatment-related adverse events were reported in 81 patients ( 22% ) in the Nivolumab arm and 179 patients ( 49% ) in the Sorafenib arm and led to discontinuation in 16 ( 4% ) and 29 ( 8% ) patients, respectively.
No new safety signals were observed with Nivolumab.
140 patients ( 38% ) in the Nivolumab arm and 170 patients ( 46% ) in the Sorafenib arm received subsequent therapy.
In conclusion, though the primary endpoint of overall survival did not achieve statistical significance versus Sorafenib, Nivolumab has shown clinically meaningful improvements in overall survival, overall response rate, and complete response rate as first-line treatment for advanced hepatocellular carcinoma.
Nivolumab has demonstrated a favorable safety profile consistent with previous reports. ( Xagena )
Source: ESMO ( European Society of Medical Oncology ) Meeting, 2019