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Safety and effectiveness of sorafenib in Japanese patients with hepatocellular carcinoma in daily medical practice: interim analysis of a prospective postmarketing all-patient surveillance study
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ABSTRACT
Background: Sorafenib was approved for treatment of unresectable hepatocellular carcinoma (HCC) in Japan in 2009. A prospective postmarketing all-patient surveillance (PMS) study was requested by Japanese authorities to confirm safety and effectiveness of sorafenib in Japanese HCC population. Methods: Patients with unresectable HCC treated with sorafenib were followed up for 12 months. Data on patient demographic characteristics, treatment status, clinical outcome, and adverse events (AEs) were collected. Results: This interim analysis included 1109 and 1065 patients evaluable for safety and effectiveness, respectively. Most patients (83.4 %) received the recommended initial dose of 400 mg twice daily. After a follow-up of 12-months, 89.8 % had discontinued treatment, most because of AEs (44.5 %) or progression (33.8 %). The most common drug-related adverse events (DRAE) were hand-foot skin reaction (51.4 %), liver dysfunction (26.4 %), diarrhea (25.1 %), and hypertension (21.6 %). The median overall survival (OS) was 348 days [95 % confidence interval (CI) 299–389 days], and the median duration of treatment was 87 days (95 % CI 78–98 days). Multivariate analyses identified baseline prognostic factors for longer OS, including female sex, low Child-Pugh score, Eastern Cooperative Oncology Group performance status 0, tumor stage I/II/III, low aspartate aminotransferase level, high hemoglobin level, hepatitis C and history of surgical resection. Conclusions: In general, the safety and effectiveness findings in this PMS were consistent with findings from previous clinical studies. Sorafenib was well tolerated and clinically useful for Japanese patients. Conclusions: Clinical trial registration number: NCT01411436 Electronic supplementary material: The online version of this article (doi:10.1007/s00535-016-1173-5) contains supplementary material, which is available to authorized users. No MeSH data available. Related in: MedlinePlus |
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Fig1: Time course of onset of drug-related adverse events (DRAE) evaluated based on the ratio of cumulative incidence rate at day 30 to that at day 365 using the Kaplan–Meier method: a DRAE occurring in the early stage of treatment (ratio ≥ 0.6); b intermediate DRAE (ratio ≥0.4 to <0.6); c DRAE occurring over the entire period (ratio <0.4). *Clinically similar terms of MedDRA were combined in one DRAE. MedDRA Medical Dictionary for Regulatory Activities Mentions: The time course of onset of DRAE is shown in Fig. 1. DRAE, including hand-foot skin reaction, hypertension, rash, platelet count decreased, increased lipase/amylase, and pyrexia, occurred predominantly in the early stage of treatment [ratio of incidence rates (day 30/day 365), ≥ 0.6], whereas diarrhea, alopecia, hemorrhagic events and ascites occurred over the entire period (ratio < 0.4). liver dysfunction, anorexia, and malaise were intermediate (ratio ≥ 0.4 to < 0.6).Fig. 1 |
View Article: PubMed Central - PubMed
Background: Sorafenib was approved for treatment of unresectable hepatocellular carcinoma (HCC) in Japan in 2009. A prospective postmarketing all-patient surveillance (PMS) study was requested by Japanese authorities to confirm safety and effectiveness of sorafenib in Japanese HCC population.
Methods: Patients with unresectable HCC treated with sorafenib were followed up for 12 months. Data on patient demographic characteristics, treatment status, clinical outcome, and adverse events (AEs) were collected.
Results: This interim analysis included 1109 and 1065 patients evaluable for safety and effectiveness, respectively. Most patients (83.4 %) received the recommended initial dose of 400 mg twice daily. After a follow-up of 12-months, 89.8 % had discontinued treatment, most because of AEs (44.5 %) or progression (33.8 %). The most common drug-related adverse events (DRAE) were hand-foot skin reaction (51.4 %), liver dysfunction (26.4 %), diarrhea (25.1 %), and hypertension (21.6 %). The median overall survival (OS) was 348 days [95 % confidence interval (CI) 299–389 days], and the median duration of treatment was 87 days (95 % CI 78–98 days). Multivariate analyses identified baseline prognostic factors for longer OS, including female sex, low Child-Pugh score, Eastern Cooperative Oncology Group performance status 0, tumor stage I/II/III, low aspartate aminotransferase level, high hemoglobin level, hepatitis C and history of surgical resection.
Conclusions: In general, the safety and effectiveness findings in this PMS were consistent with findings from previous clinical studies. Sorafenib was well tolerated and clinically useful for Japanese patients.
Conclusions: Clinical trial registration number: NCT01411436
Electronic supplementary material: The online version of this article (doi:10.1007/s00535-016-1173-5) contains supplementary material, which is available to authorized users.
No MeSH data available.
