Characteristics of patients with sorafenib-treated advanced hepatocellular carcinoma eligible for second-line treatment

Abstract

Background Regorafenib has been investigated for its efficacy and safety as a second-line treatment in patients with advanced hepatocellular carcinoma (HCC). We assessed the characteristics of patients with HCC treated with sorafenib who might be eligible for second-line treatment in general and regorafenib in particular. Methods Patients with HCC treated with sorafenib were retrospectively analyzed. We defined second-line candidate patients as maintaining Child-Pugh A and ECOG-PS ≤1 at the time of sorafenib failure. We also defined regorafenib candidate patients as follows: 1) continuing sorafenib at the time of radiological progression, 2) maintaining Child-Pugh A and ECOG-PS ≤ 1 at the time of sorafenib failure, and 3) continuing sorafenib 400 mg or more without intolerable adverse events at least 20 days of the last 28 days of treatment. Results Of 185 patients, 130 (70%) and 69 (37%) were candidates for second-line treatment and regorafenib. Child-Pugh score 6 and ECOG-PS 1 at the time of starting sorafenib were significantly lower in both second-line treatment and regorafenib candidate patients. Moreover, hand-foot skin reaction and liver failure during sorafenib treatment were associated with significantly low and high probabilities, respectively, of both Child-Pugh score > 6 and ECOG-PS > 1 at the time of sorafenib failure. Conclusion Regorafenib candidate patients after sorafenib failure are limited, and generally fewer than those who are candidates for second-line treatment. A lower Child-Pugh score and a better ECOG-PS were predictors of eligibility for second-line therapy and regorafenib treatment in sorafenib-treated patients with advanced HCC patients.

Clinical characteristics and outcomes of candidates for second‐line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma after sorafenib treatment

“…Both good liver function (Child–Pugh A) and good general condition (ECOG‐PS score of 0 or 1) were adopted as essential inclusion criteria in clinical trials that clarified the efficacy of almost all new systemic chemotherapeutic agents in HCC patients . The number of candidates for second‐line treatments after sorafenib failure was reported to range from 50.3% to 70.0% . Similarly, in our study, the proportion of candidates for second‐line treatments at first radiologic PD was 57.3%.…”

“…The reasons for ineligibility were deterioration of liver function (Child–Pugh B or C) in 38.8% and worsening of general condition (ECOG‐PS score ≥ 2) in 23.3%; these factors, in addition to tolerance to sorafenib treatment, comprised the eligibility criteria for regorafenib treatment, according to the RESORCE trial . The number of candidates eligible for regorafenib treatment was reported as 30.6–44.2%, and the rate of the intolerability to sorafenib was reported as 32.0–53.7% . In our study, the proportion of candidates for regorafenib treatment at radiologic PD was 35.0%, and the most common reason for classification into the RESORCE‐out group was intolerability to sorafenib (42.7%).…”

“…[7][8][9] However, not all patients who are refractory or intolerant to sorafenib can be switched to second-line therapy. [10][11][12][13][14] Because the efficacy and safety of regorafenib in patients who do not meet the eligibility criteria for the RESORCE trial have not been verified, the Japan Clinical Practice Guidelines for Hepatocellular Carcinoma 2017 and the Barcelona Clinic Liver Cancer (BCLC) Guidelines for Hepatocellular Carcinoma 2018 recommended regorafenib as second-line treatment for patients tolerant to sorafenib and well-preserved liver function (Child-Pugh A) after radiologic PD with sorafenib.…”

Prognostic Factors Associated with Postprogression Survival in Advanced Hepatocellular Carcinoma Patients Treated with Sorafenib Not Eligible for Second-Line Regorafenib Treatment

“…There has been only one report [4] regarding the proportion of patients meeting the eligibility criteria for the RESORCE trial at radiological PD. The authors reported that, among 185 patients who failed sorafenib treatment and had both Child-Pugh class A and an ECOG-PS score of 0 or 1 at the time of sorafenib failure, and a starting sorafenib dose of 800 mg/day, 69 patients (37.0%) were candidates for regorafenib at the time of sorafenib failure.…”

“…Thus, in patients refractory to so­ra­fenib, postprogression survival (PPS) is expected to improve by switching from sorafenib to regorafenib [2, 3]. However, not all patients who have confirmed radiological PD can switch to regorafenib therapy, because the efficacy and safety of regorafenib administration in patients who do not meet the eligibility criteria for the RESORCE trial have not been verified [4]. According to the Clinical Practice Guidelines for Hepatocellular Carcinoma 2017 in Japan and the Barcelona Clinic Liver Cancer (BCLC) Guidelines for Hepatocellular Carcinoma 2018, it is recommended that regorafenib should be indicated for patients tolerant to sorafenib and with well-preserved liver function (Child-Pugh class A) as second-line treatment after radiological PD with sorafenib.…”