Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: First-line treatment with camrelizumab and rivoceranib offers significant survival advantages over sorafenib for patients with advanced hepatocellular carcinoma (HCC), suggests research presented at the ESMO Congress 2022 in Paris, France.
Presenting author Shukui Qin, from Nanjing University of Chinese Medicine in China, said the trial was the first to show both significant progression-free survival (PFS) and overall survival (OS) benefits for the combination of an anti-PD-1/PD-L1 agent plus a small-molecule tyrosine kinase inhibitor in this patient population.
And he emphasized that the regimen “provides the longest OS seen in a front-line pivotal phase 3 study in advanced HCC to date.”
In the trial, patients with advanced HCC unsuitable for radical surgery and/or locoregional therapy were randomly assigned to receive camrelizumab 200 mg every 2 weeks plus rivoceranib 250 mg/day (n=272) or to receive sorafenib 400 mg twice daily (n=271), with both regimens continuing until loss of benefit or intolerable toxicity.
The presenter said the camrelizumab plus rivoceranib and sorafenib treatment arms were well balanced, with the majority of participants in both arms being men (83.5 vs 84.9%) from Asia (82.7 vs 82.7%) with hepatitis B viral (HBV) aetiology (76.5 vs 72.7%).
Most patients had BCLC stage C disease (86.0 vs 85.2%), a Child–Pugh score of A5 (86.8 vs 84.9%), macrovascular invasion and/or extrahepatic spread (73.5 vs 73.8%) and an alpha-fetoprotein level below 400 ng/mL (AFP; 64.7 vs 63.1%). Over half of the patients had previously received local therapy (59.2 vs 55.4%).
Primary analysis of PFS gave a median duration of 5.6 months for the combination regimen versus 3.7 months for sorafenib, translating to a significant hazard ratio (HR) of 0.52 in favour of camrelizumab plus rivoceranib.
Similarly, interim analysis of OS indicated a significant benefit with camrelizumab plus rivoceranib versus sorafenib, with median durations of 22.1 and 15.2 months, respectively, and a HR of 0.62.
And prespecified subgroup analysis indicated that the OS benefit with the combination regimen was found in Asian and non-Asian participants and regardless of baseline AFP levels and prior receipt of local therapy.
However, it appeared that patients with BCLC stage C may benefit more from the combination treatment versus sorafenib than those with stage B disease, as did those with HBV aetiology versus hepatitis C or non-viral aetiology. Patients with macrovascular invasion or extrahepatic spread also appeared to benefit more from the combination than monotherapy treatment.
Camrelizumab plus rivoceranib also achieved a significantly higher objective response rate than sorafenib (25.4 vs 5.9%), as well as a longer median duration of response (14.8 vs 9.2 months) and median time to progression (7.2 vs 3.7 months).
Turning to the safety summary, Shukui Qin said that grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 80.5% of patients given the combination regimen versus 52.0% of those given sorafenib, with serious TRAEs in 24.3% and 5.9%, respectively, and one treatment-related death in each arm.
The most common TRAEs of at least grade 3 in the camrelizumab plus rivoceranib arm were hypertension (37.5%), elevated aspartate aminotransferase (AST; 16.5%) or alanine aminotransferase (12.9%), and palmar–plantar erythrodysaesthesia (PPE; 12.1%). The most frequent TRAEs at grade 3 or worse with sorafenib were PPE (15.2%), hypertension (14.9%) and elevated AST and diarrhoea (5.2% each).
TRAEs led to dose modifications or interruption in a corresponding 80.5% and 50.2% of patients, and to discontinuation of any treatment component in 24.3% and 4.5% of cases.
“The combination of camrelizumab plus rivoceranib was generally well tolerated, with a safety profile in line with each individual agent and the underlying disease”, the presenter summarised.
He concluded: “These findings support that camrelizumab plus rivoceranib represents another new first-line treatment option for unresectable HCC.”
Discussant Robin Kate Kelley, from the University of California – San Francisco in the USA, compared the positive results for camrelizumab plus rivoceranib with those of the phase III LEAP-002 study in a similar population, also presented at the session, which failed to show an overall significant OS benefit with first-line lenvatinib plus pembrolizumab versus lenvatinib alone.
She noted that both trials found that patients with HBV aetiology had better OS than other individuals and hypothesised that the higher proportion of HBV-positive patients in the camrelizumab plus rivoceranib trial might partially explain the differences in outcome between the studies.
The discussant also questioned whether the study population is “broad enough” to extend the recommendation for camrelizumab plus rivoceranib to non-Asian populations, and whether the findings for this combination “adequately differentiate” from those of the previously reported IMbrave150 trial of first-line atezolizumab plus bevacizumab.
She concluded that the “optimal” combination of anti-angiogenic and/or immunotherapy has not yet been established and that translational analyses are required to determine this for different patient subgroups.
Nevertheless, she concluded that “[t]he advent of multiple first- and later-line treatment options marks enormous progress in HCC and provides new opportunity to individualize treatment decisions.”
Reference
LBA35 - Qin S, Chan LS, Gu S, et al. Camrelizumab plus rivoceranib vs. sorafenib as first-line therapy for unresectable hepatocellular carcinoma: A randomized, phase III trial. Ann Oncol 2022; 33 (suppl_7): S808–S869. Doi: 10.1016/annonc/annonc1089
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