Radboud Universitair Medisch Centrum

PROpel met its primary endpoint showing statistically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus placebo plus abiraterone in patients with first-line metastatic castration-resistant prostate cancer (mCRPC) unselected by homologous recombination repair mutation (HRRm) status, with benefit observed in all prespecified subgroups. Here we report the final prespecified overall survival analysis.

This was a randomised, double-blind, phase 3 trial done at 126 centres in 17 countries worldwide. Patients with mCRPC aged at least 18 years, Eastern Cooperative Oncology Group performance status 0-1, a life expectancy of at least 6 months, with no previous systemic treatment for mCRPC and unselected by HRRm status were randomly assigned (1:1) centrally by means of an interactive voice response system-interactive web response system to abiraterone acetate (orally, 1000 mg once daily) plus prednisone or prednisolone with either olaparib (orally, 300 mg twice daily) or placebo. The patients, the investigator, and study centre staff were masked to drug allocation. Stratification factors were site of metastases and previous docetaxel at metastatic hormone-sensitive cancer stage. Radiographic progression-free survival was the primary endpoint and overall survival was a key secondary endpoint with alpha-control (alpha-threshold at prespecified final analysis: 0·0377 [two-sided]), evaluated in the intention-to-treat population. Safety was evaluated in all patients who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03732820, and is completed and no longer recruiting.

Between Oct 31, 2018 and March 11, 2020, 1103 patients were screened, of whom 399 were randomly assigned to olaparib plus abiraterone and 397 to placebo plus abiraterone. Median follow-up for overall survival in patients with censored data was 36·6 months (IQR 34·1-40·3) for olaparib plus abiraterone and 36·5 months (33·8-40·3) for placebo plus abiraterone. Median overall survival was 42·1 months (95% CI 38·4-not reached) with olaparib plus abiraterone and 34·7 months (31·0-39·3) with placebo plus abiraterone (hazard ratio 0·81, 95% CI 0·67-1·00; p=0·054). The most common grade 3-4 adverse event was anaemia reported in 64 (16%) of 398 patients in the olaparib plus abiraterone and 13 (3%) of 396 patients in the placebo plus abiraterone group. Serious adverse events were reported in 161 (40%) in the olaparib plus abiraterone group and 126 (32%) in the placebo plus abiraterone group. One death in the placebo plus abiraterone group, from interstitial lung disease, was considered treatment related.

Overall survival was not significantly different between treatment groups at this final prespecified analysis.

Supported by AstraZeneca and Merck Sharp & Dohme.

A booklet was developed in Canada in 2005 to inform family caregivers of people with dementia about end-of-life care. A Dutch version was published in 2011 after evaluation and revision. Developments in research and society call for a second revision. The aim of this study was to map out users' (family caregivers and healthcare professionals) preferences regarding the look and feel, and content of the booklet. To this end, in addition to the current paper booklet, we created a prototype website and app, along with three illustration options. Twenty-one family caregivers and nineteen healthcare professionals completed a questionnaire about their preferences. Open ended questions were analyzed using content analysis, multiple-choice questions using descriptive analysis. The participants valued the question-answer format. They perceived the text as too medically oriented and they expressed a need for more inclusive language and broader information. The participants found images of people suitable for the booklet and they preferred the illustrations to be less focused on the medical context. The participants preferred the paper booklet and a website. By understanding family caregivers' and healthcare professionals' preferences, in the second revision, the booklet can be tailored to the user. It is expected that this tailoring will support informing family caregivers about end-of-life care.

Emergency General Surgery (EGS) was identified as multidisciplinary surgery performed for traumatic and non-traumatic acute conditions during the same admission in the hospital by general emergency surgeons and other specialists. It is the most diffused surgical discipline in the world. To live and grow strong EGS necessitates three fundamental parts: emergency and elective continuous surgical practice, evidence generation through clinical registries and data accrual, and indications and guidelines production: the LIFE TRIAD.