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A systematic review and network meta-analysis of second-line therapy in hepatocellular carcinoma
S Delos Santos1, S Udayakumar1, A Nguyen2
1Sunnybrook Research Institute, University of Toronto, Toronto, ON.
Background:
In patients with advanced hepatocellular carcinoma (hcc) following sorafenib failure, it is unclear which treatment is most efficacious, as treatments in the second-line setting have not been directly compared and no standard therapy exists. This systematic review and network meta-analysis (nma) aimed to compare the clinical benefits and toxicities of these treatments.
Methods:
A systematic review of randomized controlled trials (rcts) was conducted to identify phase iii rcts in advanced hcc following sorafenib failure. Baseline characteristics and outcomes of placebo were examined for heterogeneity. Primary outcomes of interest were extracted for results, including overall survival (os), progression-free survival (pfs), objective response rate (orr), grade 3/4 toxicities, and subgroups. An nma was conducted to compare both drugs through the intermediate placebo. Comparisons were expressed as hazard ratios (hrs) for os and pfs, and as risk difference (rd) for orr and toxicities. Subgroup analyses for os and pfs were also performed.
Results:
Two rcts were identified (1280 patients) and compared through an indirect network; celestial (cabozantinib vs. placebo) and resorce (regorafenib vs. placebo). Baseline characteristics of patients in both trials were similar. Both trials also had similar placebo outcomes. Cabozantinib, compared with regorafenib, showed similar os [hazard ratio (hr): 1.21; 95% confidence interval (ci): 0.90 to 1.62], pfs (hr: 1.02; 95% ci: 0.78 to 1.34) and orr (-3.0%; 95% ci: -7.6% to 1.7%). Both treatments showed similar toxicities, but there were marginally higher risks of grade 3/4 hand-foot syndrome (5%; 95% ci: 0.1% to 9.8%), diarrhea (4.8%; 95% ci: 1.1% to 8.5%), and anorexia (4.4%; 95% ci: 0.8% to 8.0%) for cabozantinib. Subgroup results for os and pfs were consistent with overall results.
Conclusions:
Overall, this nma determined that cabozantinib and regorafenib have similar clinical benefits and toxicities for second-line hcc.
Insights
Cabozantinib and regorafenib show similar efficacy and safety in advanced hepatocellular carcinoma (HCC) patients after sorafenib failure. This network meta-analysis provides crucial insights for second-line treatment decisions in HCC.
Area of Science:
- Oncology
- Hepatocellular Carcinoma (HCC) Treatment
- Clinical Trial Analysis
Background:
- Advanced hepatocellular carcinoma (HCC) patients often fail first-line sorafenib treatment.
- Second-line treatment options for advanced HCC lack direct comparisons and a standard therapy.
- This study addresses the clinical uncertainty regarding the efficacy and toxicity of available second-line treatments.
Purpose of the Study:
- To conduct a systematic review and network meta-analysis (NMA) of second-line treatments for advanced HCC post-sorafenib.
- To compare the clinical benefits, including overall survival (OS) and progression-free survival (PFS), of available therapies.
- To evaluate and compare the toxicity profiles of these second-line treatments.
Main Methods:
- Systematic review of Phase III randomized controlled trials (RCTs) in advanced HCC following sorafenib failure.
- Network meta-analysis (NMA) comparing treatments indirectly through a placebo.
- Extracted outcomes included OS, PFS, objective response rate (ORR), and Grade 3/4 toxicities; analyses included subgroup evaluations.
Main Results:
- Two RCTs (1280 patients) comparing cabozantinib and regorafenib indirectly via placebo were analyzed.
- Both cabozantinib and regorafenib demonstrated similar overall survival (HR: 1.21; 95% CI: 0.90–1.62), PFS (HR: 1.02; 95% CI: 0.78–1.34), and ORR (RD: -3.0%; 95% CI: -7.6%–1.7%).
- Toxicity profiles were comparable, with slightly higher risks for cabozantinib in hand-foot syndrome, diarrhea, and anorexia.
Conclusions:
- Cabozantinib and regorafenib offer similar clinical benefits for advanced HCC patients progressing on sorafenib.
- The NMA indicates comparable toxicity profiles between cabozantinib and regorafenib in this patient population.
- These findings suggest that both agents are viable options for second-line therapy in advanced HCC.
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