Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer : long-term survival results from the STAMPEDE trial

Background STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients. Methods We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional. Results Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69–0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57–0.76, P  0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression). Conclusions The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden

Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial

Background STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL). Methods and findings Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively. Conclusions Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC. Trial registration ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544

Pharmacist services for non-hospitalised patients

Contains fulltext : 200314.pdf (Publisher’s version ) (Open Access)BACKGROUND: This review focuses on non-dispensing services from pharmacists, i.e. pharmacists in community, primary or ambulatory-care settings, to non-hospitalised patients, and is an update of a previously-published Cochrane Review. OBJECTIVES: To examine the effect of pharmacists' non-dispensing services on non-hospitalised patient outcomes. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases and two trial registers in March 2015, together with reference checking and contact with study authors to identify additional studies. We included non-English language publications. We ran top-up searches in January 2018 and have added potentially eligible studies to 'Studies awaiting classification'. SELECTION CRITERIA: Randomised trials of pharmacist services compared with the delivery of usual care or equivalent/similar services with the same objective delivered by other health professionals. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures of Cochrane and the Effective Practice and Organisation of Care Group. Two review authors independently checked studies for inclusion, extracted data and assessed risks of bias. We evaluated the overall certainty of evidence using GRADE. MAIN RESULTS: We included 116 trials comprising 111 trials (39,729 participants) comparing pharmacist interventions with usual care and five trials (2122 participants) comparing pharmacist services with services from other healthcare professionals. Of the 116 trials, 76 were included in meta-analyses. The 40 remaining trials were not included in the meta-analyses because they each reported unique outcome measures which could not be combined. Most trials targeted chronic conditions and were conducted in a range of settings, mostly community pharmacies and hospital outpatient clinics, and were mainly but not exclusively conducted in high-income countries. Most trials had a low risk of reporting bias and about 25%-30% were at high risk of bias for performance, detection, and attrition. Selection bias was unclear for about half of the included studies.Compared with usual care, we are uncertain whether pharmacist services reduce the percentage of patients outside the glycated haemoglobin target range (5 trials, N = 558, odds ratio (OR) 0.29, 95% confidence interval (CI) 0.04 to 2.22; very low-certainty evidence). Pharmacist services may reduce the percentage of patients whose blood pressure is outside the target range (18 trials, N = 4107, OR 0.40, 95% CI 0.29 to 0.55; low-certainty evidence) and probably lead to little or no difference in hospital attendance or admissions (14 trials, N = 3631, OR 0.85, 95% CI 0.65 to 1.11; moderate-certainty evidence). Pharmacist services may make little or no difference to adverse drug effects (3 trials, N = 590, OR 1.65, 95% CI 0.84 to 3.24) and may slightly improve physical functioning (7 trials, N = 1329, mean difference (MD) 5.84, 95% CI 1.21 to 10.48; low-certainty evidence). Pharmacist services may make little or no difference to mortality (9 trials, N = 1980, OR 0.79, 95% CI 0.56 to 1.12, low-certaintly evidence).Of the five studies that compared services delivered by pharmacists with other health professionals, no studies evaluated the impact of the intervention on the percentage of patients outside blood pressure or glycated haemoglobin target range, hospital attendance and admission, adverse drug effects, or physical functioning. AUTHORS' CONCLUSIONS: The results demonstrate that pharmacist services have varying effects on patient outcomes compared with usual care. We found no studies comparing services delivered by pharmacists with other healthcare professionals that evaluated the impact of the intervention on the six main outcome measures. The results need to be interpreted cautiously because there was major heterogeneity in study populations, types of interventions delivered and reported outcomes.There was considerable heterogeneity within many of the meta-analyses, as well as considerable variation in the risks of bias