This PMS demonstrated that cabazitaxel was generally tolerated and showed promising efficacy in Japanese patients with mCRPC treated in real-world settings. Results are consistent with those of pre-registration clinical trials.

Objectives: Data on the safety and efficacy of cabazitaxel in patients aged ≥80 years with castration-resistant prostate cancer (CRPC) are limited. We report the safety (adverse drug reactions [ADRs]) and efficacy (overall survival [OS], time to treatment failure [TTF], and prostate-specific antigen [PSA] response rates) in patients aged b80 or ≥80 years treated with cabazitaxel for CRPC in clinical practice. Materials and methods: We performed post-hoc subgroup analyses of a Japanese post-marketing surveillance study involving 662 patients with CRPC treated with cabazitaxel between September 2014 and June 2016. Results: In patients aged b80 (n = 610) and ≥80 years (n = 49), median PSA at baseline was 168.7 and 109.0 ng/mL, and 86.7% and 83.7% of patients were previously treated with enzalutamide and/or abiraterone. ADRs (all grade) occurred in 77.2% and 79.6% of patients aged b80 and ≥80 years, with grade three/worse ADRs in 61.8% and 63.3% of patients. Hematologic toxicities were the most common grade three/worse ADRs, including neutropenia, febrile neutropenia, and anemia in both subgroups. No specific ADRs were observed in patients aged ≥80 years. The PSA response and median OS and TTF were 28.3%, 292 days, and 116 days in patients aged ≥80 years, and 29.7%, 319 days, and 125 days in patients aged b80 years. Conclusion: Cabazitaxel could be a treatment option for CRPC in patients aged ≥80 years based on its safety and efficacy profiles. This is the first report to investigate the safety and efficacy of cabazitaxel in patients aged ≥80 years with CRPC.

Background: The recommended starting dose of cabazitaxel for castration-resistant prostate cancer (CRPC) is 25 mg/m 2 in Japan and Europe. Although lower doses are established alternatives based on randomized controlled trials, the safety and efficacy of 25 and 20 mg/m 2 in real-world settings are not well established. Therefore, we investigated the safety and efficacy of cabazitaxel at the recommended starting dose or a lower dose (20 mg/m 2) in real-world clinical practice. Methods: We compared the safety and efficacy of cabazitaxel between patients who received cabazitaxel at starting doses of 25 and 20 mg/m 2 (C25 and C20, respectively) in a Japanese post-marketing surveillance study of 662 patients with docetaxel-refractory CRPC. Safety was assessed in terms of adverse drug reactions (ADRs). Prostate-specific antigen (PSA) response rate, overall survival (OS), and time-to-treatment failure (TTF) were compared between the C25 and C20 groups in unmatched patients and after applying propensity score matching. Results: The C20 and C25 groups comprised 190 and 159 patients without matching and 112 patients per group after matching. In unmatched patients, any-grade (C25 vs C20: 89.3% vs 78.4%, Fisher's p < 0.01) and grade ≥ 3 (81.1% vs 61.1%) ADRs were more frequent in the C25 group. Neutropenia (any grade: 61.6% vs 54.2%; grade ≥ 3: 55.3% vs 42.6%) and febrile neutropenia (grade ≥ 3: 30.2% vs 14.7%) were more frequent in the C25 group. In matched patients, the PSA response rate (reduction in PSA ≥30% from a baseline ≥5 ng/mL) was 26.4 and 32.0% in the C20 and C25 groups, respectively, median OS was 291 days (95% CI 230-not reached) versus not reached (hazard ratio 0.73, 95% CI 0.50-1.08), and TTF favored C25 (hazard ratio 0.75, 95% CI 0.57-0.99).

Background We aimed to evaluate relationships between clinical outcomes and explanatory variables by network clustering analysis using data from a post marketing surveillance (PMS) study of castration-resistant prostate cancer (CRPC) patients. Methods The PMS was a prospective, multicenter, observational study of patients with metastatic, docetaxel-refractory CRPC treated with cabazitaxel in Japan after its launch in 2014. Graphical Markov (GM) model-based simulations and network clustering in ‘R’ package were conducted to identify correlations between clinical factors and outcomes. Factors shown to be associated with overall survival (OS) in the machine learning analysis were confirmed according to the clinical outcomes observed in the PMS. Results Among the 660 patients analyzed, median patient age was 70.0 years, and median OS and time-to-treatment failure (TTF) were 319 and 116 days, respectively. In GM-based simulations, factors associated with OS were liver metastases, performance status (PS), TTF, and neutropenia (threshold 0.05), and liver metastases, PS, and TTF (threshold 0.01). Factors associated with TTF were OS and relative dose intensity (threshold 0.05), and OS (threshold 0.01). In network clustering in ‘R’ package, factors associated with OS were number of treatment cycles, discontinuation due to disease progression, and TTF (threshold 0.05), and liver and lung metastases, PS, discontinuation due to adverse events, and febrile neutropenia (threshold 0.01). Kaplan–Meier analysis of patient subgroups demonstrated that visceral metastases and poor PS at baseline were associated with worse OS, while neutropenia or febrile neutropenia and higher number of cabazitaxel cycles were associated with better OS. Conclusions Neutropenia may be a predictive factor for treatment efficacy in terms of survival. Poor PS and distant metastases to the liver and lungs were shown to be associated with worse outcomes, while factors related to treatment duration were shown to positively correlate with better OS.

IntroductionThis analysis investigated the relationship between baseline fasting pancreatic β-cell function and efficacy in Japanese patients with type 2 diabetes (T2D) treated with once-weekly dulaglutide 0.75 mg (dulaglutide) or once-daily liraglutide 0.9 mg (liraglutide) for up to 52 weeks.MethodsIn a 52-week study of monotherapy in Japanese patients with T2D, patients were categorized into three subgroups defined by tertiles (low, medium, and high) of baseline values of three pancreatic β-cell function parameters [fasting C-peptide, C-peptide index, and secretory units of islets in transplantation (SUIT) index]. Associations between these parameters and efficacy [defined by changes from baseline in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), postprandial blood glucose (PBG), mean of all meals blood glucose excursion, and body weight] in the dulaglutide group (280 patients) or the liraglutide group (137 patients) were evaluated.ResultsPatients in the subgroups with high insulin-secreting ability (based on pancreatic β-cell function) were younger and had shorter disease duration and higher body mass index compared to those with low insulin-secreting ability. No specific trend was observed between baseline pancreatic β-cell function and changes in HbA1c or FBG. Reductions from baseline in mean PBG and excursion were greatest for patients in the low β-cell function tertiles. Inconsistent trends in body weight were observed across the treatment groups and β-cell function parameters.ConclusionIn Japanese patients with T2D, changes in HbA1c and body weight after 52 weeks of treatment with dulaglutide or liraglutide could not be predicted by patients’ fasting pancreatic β-cell function before treatment.Clinical Trial RegistrationClinicalTrials.gov (NCT01558271).FundingEli Lilly K.K. (Kobe, Japan).