An exploratory analysis of findings from the phase III REFLECT trial suggests that an objective response could serve as a surrogate endpoint for prolonged overall survival (OS) in patients with hepatocellular carcinoma (HCC).

Masatoshi Kudo, MD, PhD, of the Kindai University Faculty of Medicine in Japan, and fellow REFLECT investigators used the data from this large, global, randomized trial, which was designed to establish the noninferiority of first-line lenvatinib versus sorafenib in 954 patients with unresectable HCC, to analyze the correlation between objective response and OS irrespective of treatment.

The researchers found that median OS reached 22.4 months for patients who had a complete or partial response to either lenvatinib or sorafenib. In contrast, median OS reached only 11.4 months for nonresponders—those with stable disease, progressive disease, or unknown response status.

In a multivariate analysis, the typical predictors of OS surfaced—factors such as macroscopic portal vein invasion, baseline alpha-fetoprotein level, the number of tumor sites at baseline, and liver involvement. However, objective response also emerged as a strong independent predictor of prolonged OS, with a hazard ratio of 0.61 (95% CI [0.49, 0.76]; p < 0.001).

If validated in other studies, use of objective response as a surrogate for OS could offer two key advantages. First, if applied in clinical trials of advanced HCC, it could enable faster readout regarding the benefit of investigational therapies, potentially streamlining the approval of new agents. Second, it could enable clinicians to promptly identify those patients who are unlikely to derive a survival benefit from a particular therapy, triggering an early switch to another treatment that might prove more fruitful.

This article is news of a study presented at the 2019 Gastrointestinal Cancers Symposium. Read the original here.