Early sorafenib‐related adverse events predict therapy response of TACE plus sorafenib: A multicenter clinical study of 606 HCC patients

Abstract

The purpose of our study was to test the hypothesis that sorafenib-related dermatologic adverse events (AEs) as an early biomarker can predict the long-term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S). The intermediate-stage hepatocellular carcinoma patients who received either TACE-S or TACE-alone treatment were consecutively included into analysis. In the TACE-S group, patients with grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those with < grade 2 were defined as nonresponders. In the TACE-S group, the median overall survival (OS) of the responders was significantly longer than that of nonresponders (28.9 months vs. 16.8 months, respectively; p 5 0.004). Multivariate analysis demonstrated that nonresponders were significantly associated with an increased risk of death compared with responders (HR 5 1.9; 95% confidence Interval-CI: 1.3-2.7; p 5 0.001). The survival analysis showed that the median OS was 27.9 months (95% CI: 25.0-30.8) among responders treated with TACE-S vs.18.3 months (95% CI: 14.5-22.1) among those who received TACE-alone (p 5 0.046). The median time to progression was 13.1 months (95% CI: 4.4-21.8) in the TACE-S group, a duration that was significantly longer than that in the

mRECIST response combined with sorafenib‐related adverse events is superior to either criterion alone in predicting survival in HCC patients treated with TACE plus sorafenib

“…Because of the lack of reliable biomarkers for sorafenib use, dermatologic AEs related to sorafenib have become widely recognized as surrogate markers for efficacy in patients with HCC . The prognostic value of these dermatologic AEs was also confirmed in our very recent multicentre clinical study of 606 HCC patients, which demonstrated that sorafenib‐related dermatologic AEs may be used as clinical indicators to identify responders to sorafenib and those who are more likely to benefit from TACE‐S treatment . Indeed, patients who develop dermatologic AEs might constitute the ideal population in whom the addition of sorafenib would work.…”

“…AEs were evaluated every 2 weeks by two independent physicians (W. Bai and G. Han). Consistent with previous studies, grade 2 was selected as the cut‐off . We defined patients with skin toxicity ≥ Grade 2 as dermatologic responders and patients with skin toxicity < Grade 2 as dermatologic nonresponders.…”

“…Therefore, evaluating the efficacy of TACE‐S by mRECIST alone is not sufficient. Interestingly, several studies, including our recent article, have confirmed that the dermatologic adverse events (AEs) that arise during sorafenib treatment can be used as an early and significant prognostic factor of survival …”

“…Interestingly, several studies, including our recent article, have confirmed that the dermatologic adverse events (AEs) that arise during sorafenib treatment can be used as an early and significant prognostic factor of survival. [20][21][22][23] Because mRECIST can be used to assess the primary tumor response after locoregional or systemic therapy and dermatologic AEs can reflect the efficacy of systematic sorafenib treatment, we postulated that combining the mRECIST response with dermatologic AEs may comprehensively and accurately predict survival among HCC patients treated with TACE-S. Therefore, we aimed to combine these two criteria to evaluate the response to TACE-S treatment of patients with unresectable HCC.…”

Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma

“…beyond the Milan criteria), TACE barely accomplished a 3-year survival rate of 30% even in experienced centers [9,10]. The use of TACE with External Beam Radiotherapy [16] or Sorafenib [17,18] also failed to demonstrate a satisfactory patient survival. Suboptimal survival (3-year survival of ~20%) has also been reported with Yttrium-90 selective internal radiation therapy in patients with intermediate-stage HCC deemed unsuitable for LT [19][20][21].…”