Summary Background Hepatorenal syndrome and acute kidney injury are common complications of decompensated cirrhosis, and terlipressin is recommended as first‐line vasoconstrictor therapy. However, data on its use outside of clinical trials are lacking. Aims To assess practice patterns and outcomes around vasoconstrictor use for hepatorenal syndrome in UK hospitals. Methods This was a multicentre chart review study. Data were extracted from medical records of patients diagnosed with hepatorenal syndrome and treated by vasoconstrictor drugs between January 2013 and December 2017 at 26 hospitals in the United Kingdom. The primary outcome was improvement of kidney function, defined as complete response (serum creatinine improved to ≤1.5 mg/dL), partial response (serum creatinine reduction of ≥20% but >1.5 mg/dL) and overall response (complete or partial response). Other outcomes included need for dialysis, mortality, liver transplantation and adverse events. Results Of the 225 patients included in the analysis, 203 (90%) were treated with terlipressin (median duration, 6 days; range: 2‐24 days). Mean (±standard deviation) serum creatinine at vasopressor initiation was 3.25 ± 1.64 mg/dL. Terlipressin overall response rate was 73%. Overall response was higher in patients with mild acute kidney injury (baseline serum creatinine <2.25 mg/dL), compared to those with moderate (serum creatinine ≥2.25 mg/dL and <3.5 mg/dL) or severe (serum creatinine ≥3.5 mg/dL). Ninety‐day survival was 86% for all patients (93% for overall responders vs 66% for treatment nonresponders, P < 0.0001). Conclusion Terlipressin is the most commonly prescribed vasoconstrictor for patients with hepatorenal syndrome in the United Kingdom. Treatment with terlipressin in patients with less severe acute kidney injury (serum creatinine <2.25 mg/dL) was associated with higher treatment responses, and 90‐day survival.

Aims:To describe the incidence and identify prognostic factors of central nervous system (CNS) adverse events (AEs) and any AEs (CNS, skin rash, or fracture) and evaluate the healthcare resource utilization (HCRU), direct medical costs, and therapy discontinuation associated with these AEs among non-metastatic prostate cancer (nmPC) patients who received secondary hormone therapies. Methods and results: nmPC patients who had initiated secondary hormonal therapy with enzalutamide, bicalutamide, or abiraterone 1 year after androgen deprivation therapy (ADT) were identified in the MarketScan database. Survival analyses were used to describe the incidence of CNS or any AEs. Annual HCRU and costs were compared across patient groups (CNS AE vs no CNS AE; any AE vs no AE) using propensity score weighted generalized linear models. Multivariate Cox proportional hazards models were used to identify AE predictors and compare risks of discontinuation. Results: The analysis included 532 patients who initiated secondary hormonal therapies, among whom 201 (38%) and 244 (46%) experienced a CNS AE and any AE, respectively. Median times to CNS AE and any AE from therapy initiation were 17.90 and 11.00 months, respectively. Predictors of any AE were any AE in the baseline period (6 months before starting therapy), Charlson Comorbidity Index (CCI) score (1 vs 0), surgical castration, and older age. Predictors of CNS AEs were CNS AE in the baseline period and CCI score (1 vs 0). CNS and any AEs were associated with significantly higher HCRU. CNS AEs were associated with significantly higher incremental total medical costs ($18,522). CNS AEs and any AEs significantly increased therapy discontinuation risk by 48% and 38%, respectively. Conclusions: AEs increase the economic burden and therapy discontinuation among nmPC patients receiving secondary hormonal therapies subsequent to ADTs. These patients should be carefully evaluated for AEs to reduce therapy discontinuation, HCRU, and direct medical costs. ARTICLE HISTORY

Background Second-generation androgen receptor inhibitors (ARIs) have been associated with adverse events (AEs) such as fatigue, falls, fractures, and rash in non-metastatic castration-resistant prostate cancer (nmCRPC) patients as identified in clinical trials. The objectives of this study were to describe the incidence and management of AEs in patients receiving apalutamide and enzalutamide. Methods This retrospective chart review study was conducted in nmCRPC-treating sites in the United States. Patients starting apalutamide or enzalutamide between February 1, 2018 and December 31, 2018 were included and any AEs they experienced were recorded. AEs, including those considered to be of special interest as defined in the pivotal clinical trials of the second-generation ARIs, were analyzed and grouped retrospectively in this study. Detailed chart data (patient demographics, clinical characteristics, treatment history, type of AE, outcomes, and resource utilization) were then collected for a randomly selected subset among patients with ≥1 AE to characterize AEs and their management. Descriptive results were summarized. Results Forty-three sites participated in the study. A total of 699 patients were included, of whom 525 (75.1%) experienced ≥1 AE. The most common AEs were fatigue/asthenia (34.3%), hot flush (13.9%), and arthralgia (13.6%). In the subset of 250 patients randomly selected from those who experienced ≥1 AE, patients were primarily White (72.0%), the mean age was 71 years, 86.0% had an Eastern Cooperative Oncology Group score of 0–1 at nmCRPC diagnosis, and the average prostate specific antigen (PSA) value at diagnosis was 23.2 ng/mL. PSA-doubling time < 10 months was chosen as reason to initiate treatment in 40% of patients. The median duration of follow-up was 1.1 years, with 14.4% of patients progressing to metastasis by end of study period. Grade 3–4 and Grade 5 AEs occurred in 14.4 and 0.4% of patients, respectively. Actions taken to manage AEs included AE-directed treatment (38.0%), ARI discontinuation (10.4%), dose reduction (7.6%), and AE-related hospitalization (4.8%). Conclusions This study highlights the burden of AEs among nmCRPC patients treated with apalutamide or enzalutamide, providing a relevant real-world benchmark as clinical trial evidence and the treatment landcape for nmCRPC continues to evolve.

No abstract

Background: Patients with platinum-resistant ovarian cancer have a poor prognosis. Effective treatment options for these patients are limited. In this study (ANNIE), we evaluate the activity of niraparib combined with anlotinib in patients with platinum resistant recurrent ovarian carcinoma. Methods:The ANNIE trial (NCT04376073) was a multicentre, single-arm, phase II study that evaluated the safety and activity of niraparib combined with anlotinib in patients with platinum resistant recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer cancer, and with measurable disease according to the Response Evaluation Criteria in Solid Tumors. Patients received oral niraparib 300mg/ 200mg once daily continuously and anlotinib 12mg on day 1-14 of each 21-day cycle thereafter until disease progression or intolerable toxicity. The primary objective was to assess objective response rate according to RECIST version 1.1. 40 cases are planned to be enrolled.Results: Between May 22, 2020 and April 22, 2021, we enrolled 40 patients. Patients had received a median of four (range, 2-9) previous lines of therapy, only 3 patients had a deleterious germline BRCA1/2 mutation. The cut-off date of analysis was May 1, 2021, the median follow-up was 7.6 months (range, 0.2e11.1). At data cutoff, all but ten (2 voluntarily withdrew, 8 with progressive disease) of the patients were still on treatment. Twenty-six patients underwent imaging evaluation. The confirmed best overall response assessment showed 13 with partial responses, yielding the ORR of 50.0% (95% CI, 29.4%w70.6%). The median duration of response and the median PFS were not reached. Drug-related grade 3 or worse treatment-emergent adverse events were occurred in 32.5% patients. The most common treatment emergent adverse events was hand-foot skin reaction (47.5%). No treatment-related death was recorded.Conclusions: Niraparib in combination with anlotinib showed promising antitumor activity and tolerable toxicity in patients with platinum resistant recurrent ovarian cancer.Clinical trial identification: NCT04376073.