Dataset Information

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.

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.

Clinical trial registration number

NCT01411436.

SUBMITTER: Kaneko S

PROVIDER: S-EPMC5037148 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Kaneko Shuichi S Ikeda Kenji K Matsuzaki Yasushi Y Furuse Junji J Minami Hironobu H Okayama Yutaka Y Sunaya Toshiyuki T Ito Yuichiro Y Inuyama Lyo L Okita Kiwamu K

Journal of gastroenterology 20160301 10

<h4>Background</h4>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.<h4>Methods</h4>Patients with unresectable HCC treated with sorafenib were followed up for 12 months. Data on patient demographic characteristics, treatment status, clinical outcome, and adverse event ...[more]

PMID: 26931117

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Project description:BackgroundEculizumab, a humanized monoclonal antibody targeted to terminal complement protein C5, is approved in Japan for treatment of patients with anti-acetylcholine receptor antibody-positive (AChR+) generalized myasthenia gravis (gMG) whose symptoms are difficult to control with high-dose intravenous immunoglobulin (IVIg) therapy or plasmapheresis.MethodsThis interim analysis of mandatory post-marketing surveillance in Japan assessed the safety and effectiveness of eculizumab at 26 weeks after treatment initiation in patients with AChR+ gMG.ResultsData were available for 40 adult patients in Japan [62.5% (25/40) female; mean age at eculizumab initiation, 51.0 years]. Fifteen patients had a history of thymoma. Six patients were excluded from the effectiveness analysis set due to participation in the open-label extension part of the phase III, randomized, double-blind, placebo-controlled REGAIN study [ClinicalTrials.gov identifier: NCT02301624]. After 26 weeks' follow up, 32 patients (80%) were continuing eculizumab treatment. Adverse drug reactions were reported by seven patients [most frequently headache (n = 3)]. One death was reported during eculizumab treatment (relationship unclear as determined by the treating physician) and there was one death 45 days after the last dose (considered unrelated). No meningococcal infections were reported. Mean (standard deviation) changes from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores were -3.7 (2.61) (n = 27) and -5.6 (3.50) (n = 26), respectively, at 12 weeks, and -4.3 (2.72) (n = 26) and -5.6 (4.02) (n = 24), respectively, at 26 weeks. Improvements in MG-ADL and QMG scores were generally similar in patients with/without a history of thymoma. Frequency of IVIg use decreased following eculizumab initiation.ConclusionIn a real-world setting, eculizumab was effective and well tolerated for the treatment of AChR+ gMG in adult Japanese patients whose disease was refractory to IVIg or plasmapheresis. These findings are consistent with the efficacy and safety results from the global phase III REGAIN study of eculizumab.

Project description:This all-case postmarketing surveillance (PMS) survey (101 centers; February 15, 2017, to March 3, 2020) captured factors that impact the safety and effectiveness of newly initiated pembrolizumab monotherapy for the treatment of radically unresectable melanoma in Japan. Eligible patients were enrolled both retrospectively and prospectively, and followed up at 1, 3, 6, and 12 months. Safety assessments included treatment-related adverse events (TRAEs), adverse events of special interest (AEOSIs) from the Japanese Risk Management Plan (J-AEOSIs), and J-AEOSIs related to pembrolizumab. Effectiveness assessments included objective response rate (ORR; complete response/partial response) and disease control rate (DCR) according to the RECIST criteria. Overall, 294 and 236 patients comprised the safety and effectiveness (RECIST) assessment sets, respectively. Median (range) age of the patients was 70 (22-94) years, and the majority (60.4%) received pembrolizumab as first-line therapy. The most common type of melanoma was cutaneous (41.5%), followed by mucosal (29.3%), acral (24.8%), and unknown (4.4%). Overall, 45.2% and 24.8% of patients experienced TRAEs and AEOSIs, respectively. In total, 24.8% and 9.2% of patients experienced any-grade and grade ≥3 pembrolizumab-related AEOSIs, respectively. The most common grade ≥3 pembrolizumab-related AEOSIs were endocrine disorders and liver dysfunction (2.4% each), followed by colitis/severe diarrhea (2.0%), interstitial lung disease (1%), and type 1 diabetes (0.7%). No grade 5 J-AEOSIs were observed. ORR was 16.5% at the 1-year follow-up: mucosal melanoma (20%), acral melanoma (10%), and cutaneous melanoma (17.5%). ORR was higher among patients who did not receive versus those who did receive previous systemic therapy across all three melanoma types. DCR was 52.1% at the 1-year follow-up: cutaneous melanoma (57.3%), acral melanoma (51.7%), and mucosal melanoma (43.1%). This all-case PMS survey confirmed the real-world safety and effectiveness of pembrolizumab monotherapy for the treatment of radically unresectable melanoma in Japan.

Project description:Abstract Background Direct oral anticoagulants (DOACs) are the recommended first‐line therapy for ischemic stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). However, the safety and effectiveness of edoxaban for this indication requires monitoring over the long term in real‐world settings. Methods ETNA‐AF‐Japan (trial no. UMIN000017011) was a prospective, multicenter observational study (part of postmarketing surveillance in Japan). NVAF patients due to receive edoxaban to prevent ischemic stroke were enrolled between 13 April 2015 and 30 September 2017. Results A total of 11 569 patients were enrolled. For the 11 111 patients (female, 40.6%) whose data comprised the safety analysis set, age, body weight, creatinine clearance (CLcr), and CHADS2 score were 74.2 ± 10.0 years, 60.0 ± 12.7 kg, 63.9 ± 25.8 mL/min, and 2.2 ± 1.3, respectively (mean ± SD). The majority (86.3%) received edoxaban in accordance with package insert information. The mean duration of treatment was 561.9 ± 261.2 days. The annual incidence (95% confidence interval) of all bleeding events and major bleeding events was 5.60% (5.25%–5.98%) and 1.02% (0.88%–1.18%), respectively. The annual incidence of ischemic stroke (excluding transient ischemic attack, TIA) or systemic embolism was 1.08% (0.93%–1.25%). Multivariate analysis showed low body weight, low CLcr, history of gastrointestinal bleeding, anemia, and use of an antiplatelet agent to be associated with major bleeding, and history of ischemic stroke or TIA, vascular disease, and antiplatelet agent use to be associated with ischemic stroke (excluding TIA) or systemic embolism. Conclusions These results provide real‐world evidence for the long‐term good safety and effectiveness profile of edoxaban in Japanese NVAF patients under clinical practice. This prospective, multicenter observational study was carried out to evaluate the safety and effectiveness of edoxaban as first‐line therapy to prevent ischemic stroke in Japanese patients with nonvalvular atrial fibrillation (NVAF). Annual incidence (95% confidence interval) of all bleeding events, major bleeding events, and ischemic stroke (excluding transient ischemic attack, TIA) or systemic embolism was 5.60% (5.25%–5.98%), 1.02% (0.88%–1.18%), and 1.08% (0.93%–1.25%), respectively (safety analysis set, 11 111; effectiveness analysis set, 11 063; mean duration of treatment, 561.9 ± 261.2 days). These results add to the evidence for the long‐term good safety and effectiveness profile of edoxaban in Japanese patients with NVAF in a real‐world clinical setting.

Dataset Information

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.

Background

Methods

Results

Conclusions

Clinical trial registration number

Publications

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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