Large-scale, prospective observational study of regorafenib in Japanese patients with advanced gastrointestinal stromal tumors in a real-world clinical setting.

Background: Regorafenib improves overall survival (OS) of patients with advanced progressive gastrointestinal stromal tumors (GISTs) after standard chemotherapy in phase III trials in the 3rd-line setting. This large-scale, prospective observational study evaluated the safety and effectiveness of regorafenib in Japanese patients with GIST in a real-world clinical setting. Methods: Patients with GIST received oral regorafenib at a maximum daily dose of 160 mg for weeks 1-3 of each 4-week cycle (dose could be modified at investigator's discretion). The primary objective was to assess safety, particularly significant adverse drug reactions (ADRs), as well as the frequency of occurrence of ADRs, hand and foot syndrome (HFS), discontinuation of treatment due to disease progression and adverse events. A Cox proportional hazards model was used to evaluate associations between OS or time to treatment failure (TTF) and baseline characteristics or HFS. Results: Between August 2013 and March 2021, 143 evaluable patients were enrolled. ADRs occurred in 90.2% of patients and led to treatment discontinuation in 28.3%. The most frequent ADRs were HFS, hypertension, and liver injury. The overall response rate was 11.3% and disease control rate 56.5% (RECIST) based on investigators' assessments. Median OS was 17.4 months (95% CI 14.24-23.68). Median TTF was 5.3 (95% CI 4.0-6.5) months. Improved OS and TTF responses occurred in patients with an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1. Conclusion: The outcomes in this real-world study were consistent with those seen in clinical trials. No new safety concerns were identified. Clinical trial registration: https://clinicaltrials.gov, identifier NCT01933958.

Large-Scale, Prospective Observational Study of Regorafenib in Japanese Patients with Metastatic Colorectal Cancer in a Real-World Clinical Setting.

BACKGROUND: Regorafenib improved the overall survival (OS) of patients with metastatic colorectal cancer (mCRC) who progress after standard therapies in two phase III trials. The present large-scale prospective observational study evaluated the safety and effectiveness of regorafenib administered to Japanese patients with mCRC in real-life setting. MATERIALS AND METHODS: Patients with mCRC were prospectively registered and initially received ≤160 mg oral regorafenib daily, at the investigator's discretion, for weeks 1-3 of each 4-week cycle. The study's primary aim was to assess safety, particularly unexpected clinically significant adverse drug reactions (ADRs). A Cox's proportional hazards model was used to evaluate the association between OS, hand-foot skin reaction (HFSR), and baseline characteristics. RESULTS: We evaluated 1,227 of 1,301 patients (enrolled from March 2013 to May 2015). ADRs occurred in 89.3% of patients (mostly within the first 4 weeks) and were a major reason for discontinuing treatment. The most frequent ADRs were HFSR, liver injury, and hypertension. The cumulative incidence of HFSR and liver injury was higher in patients who initially received 160 mg than in those who received ≤120 mg. The incidence of hypertension and fatigue was similar between groups. Median OS was 6.9 months (95% confidential interval, 6.4-7.4). OS was associated with early onset of HFSR and good performance status (PS) but not with the initial dose. CONCLUSION: The outcomes of this study were consistent with those of clinical trials. There were no new safety concerns. Regorafenib treatment would not be recommended for patients with higher PS. IMPLICATIONS FOR PRACTICE: Previous clinical trials demonstrated regorafenib improved overall survival in patients with metastatic colorectal cancer who progress after standard chemotherapies. Because the eligibility criteria of the trials were restricted compared with a real-world setting, the data from the trials may not fully represent the profiles of regorafenib in clinical practice. This large-scale observational study showed that the safety and effectiveness of regorafenib in clinical practice were generally consistent with previous trials. The majority of patients reported adverse drug reactions within the first 4 weeks, most commonly hand-foot skin reaction. Regorafenib treatment would not be recommended for patients with higher performance status.

Post-marketing surveillance of gadobutrol for contrast-enhanced magnetic resonance imaging in Japan.

PURPOSE: To evaluate the safety of gadobutrol for magnetic resonance imaging in a prospective, non-interventional, post-marketing surveillance in Japan. MATERIALS AND METHODS: Gadobutrol was administered in accordance with Japanese prescribing information over a 2-year enrollment period, using a standardized questionnaire to collect information. The primary outcome was the incidence of adverse reactions (ARs) following gadobutrol injection. RESULTS: Questionnaire data were analyzed for 3337 patients (age, 58.1 ± 17.4 years [mean±SD]). Gadobutrol was administered at a dose of 0.10 ± 0.02 mL/kg body weight. Thirty-three patients were observed to have 42 ARs suspected to be due to gadobutrol, an incidence proportion of 0.99%; 29 ARs were acute (<1 h post-injection)-including one case of severe acute AR (0.03%). Patient subpopulations (with hepatic, renal, cardiovascular diseases) did not differ markedly in AR proportions categorized by age, sex, presence of comorbidity, or imaging indication. No cases of nephrogenic systemic fibrosis were reported. Investigators rated images as improved or profoundly improved following gadobutrol injection in 91.1% of examinations. CONCLUSION: Gadobutrol was well tolerated with a good safety profile in this post-marketing surveillance of a large patient population in Japan.