Inducing tolerability of adverse events increases sorafenib exposure and optimizes patient's outcome in advanced hepatocellular carcinoma

Abstract

In patients with advanced hepatocellular carcinoma, sorafenib dose adjustments based on inducing tolerability of relevant adverse events prolong drug exposure and maximize survival.

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. [20][21][22] 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. 23 Indeed, patients who develop dermatologic AEs might constitute the ideal population in whom the addition of sorafenib would work.…”

“…Furthermore, the significant differences found in these studies can be attributed to ignorance of the response to therapy. 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 .…”

“…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.…”

First- and Second-Line Targeted Systemic Therapy in Hepatocellular Carcinoma—An Update on Patient Selection and Response Evaluation

“…In their cohort, HFS was not associated with OS or TTP, but BCLC stage was a negative independent prognostic factor [18]. In this regard, Ponziani et al found that adjustment of the sorafenib dose because of relevant side effects, to induce tolerability rather than stopping the drug, prolonged OS and TTP, and achieved even better results compared to the treatment group with minor side effects and unchanged treatment with 800 mg per day (OS 12.5 vs. 5.7 months, HR = 0.4, p < 0.0001, and TTP 9.5 vs. 3 months, HR = 0.3, p < 0.0001) [19]. A Japanese group performed a retrospective, propensity score matching analysis to investigate the effect of starting the treatment with an initial dosage of 400 mg per day vs. the recommended 800 mg per day (including the option to adjust the dose depending on tolerance and side effects).…”