Real-world data of sequential sorafenib followed by regorafenib in unresectable HCC

An interim analysis of the REFINE study demonstrated that, in real-world practice, most patients receive regorafenib as second-line after sorafenib. Efficacy and safety of regorafenib were similar to those in the clinical trials in both the overall cohort and in patients who discontinued sorafenib.

For patients with hepatocellular carcinoma (HCC) who are not or who are no longer candidates for locoregional therapy, systemic therapy with sorafenib is the current standard-of-care [1]. Recently, the RESORCE trial showed systemic treatment with regorafenib to be effective after progression on sorafenib [2].

The REFINE study was designed to evaluate the safety and effectiveness of second-line treatment with regorafenib in patients with HCC in real-world practice. This prospective, observational study aims to recruit 1,000 patients with unresectable HCC for whom a decision to treat with regorafenib was made by the treating physician prior to enrolment according to the local health authority approved label. Primary endpoint of REFINE is the incidence of treatment-related adverse events and dose modifications due to treatment-related adverse events. Secondary endpoints include overall survival (OS) and progression-free survival (PFS; investigator assessed). An interim analysis was performed after the first 500 patients were on study for at least 4 months [3]. Of these 500 patients, 498 received regorafenib and were evaluable. Patients were classified as Child-Pugh A 67%, B 11%, C 1%, and missing/not evaluable 21%.

Most patients (98%; n=490) had received prior systemic therapy; 97% (n=482) had received prior sorafenib. The median duration of prior sorafenib was 4.8 months, 45% (n=216) had a last daily sorafenib dose of 800 mg, and 8% (n=40) had a treatment-related adverse event leading to sorafenib discontinuation. Regorafenib was second-line treatment in 81% of patients (n=403), third-line or higher in 17% (n=87), and first-line in 2% (n=8).

Median OS for patients who received regorafenib in any line (n=498) was 13.2 months. Median OS for patients who received regorafenib in second line after sorafenib (n=398) was 14.8 months. Median OS for patients who received regorafenib in third or later line (n=87) was 8.3 months.

Among all treated patients, the most frequent treatment-related adverse events (any grade) were hand–foot skin reaction (30%), diarrhoea (21%), fatigue (16%), and decreased appetite (14%). In patients who discontinued sorafenib due to adverse events (n=40), the most frequent treatment-related adverse events (any grade) were diarrhoea (25%), hand–foot skin reaction (20%), abdominal pain (15%), and decreased appetite (13%).

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   1. Llovet JM, et al. N Engl J Med 2008; 359: 378-390.
   2. Bruix J, et al. Lancet 2017;389:56-66.
   3. Merle P, et al. ASCO Virtual Meeting, 29-31 May 2020, Abstract e16680.

Posted on 17 September 202019 September 2020