Pembrolizumab plus Olaparib in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort A Study

Metastatic castration-resistant prostate cancer; Olaparib; PembrolizumabCáncer de próstata metastásico resistente a la castración; Olaparib; PembrolizumabCàncer de pròstata metastàtic resistent a la castració; Olaparib; PembrolizumabBackground Pembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC). Objective To evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC. Design, setting, and participants Cohort A of the phase 1b/2 KEYNOTE-365 study enrolled patients with molecularly unselected, docetaxel-pretreated mCRPC whose disease progressed within 6 mo of screening. Intervention Pembrolizumab 200 mg intravenously every 3 wk plus olaparib 400-mg capsule or 300-mg tablet orally twice daily. Outcome measurements and statistical analysis The primary endpoints were safety, confirmed prostate-specific antigen (PSA) response rate, and objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, by blinded independent central review. The secondary endpoints included radiographic progression-free survival (rPFS) and overall survival (OS). Results and limitations Of 104 enrolled patients, 102 were treated. The median age was 70 yr (interquartile range [IQR], 65–76), and 59 patients (58%) had measurable disease as per RECIST v1.1. The median time from the first dose to database cutoff was 24 mo (IQR, 22–47). The confirmed PSA response rate was 15%. The confirmed ORR was 8.5% (five partial responses) for patients with measurable disease. The median rPFS was 4.5 mo (95% confidence interval [CI], 4.0–6.5) and median OS was 14 mo (95% CI, 10.4–18.2). Clinical activity was consistent across the programmed death ligand 1 (PD-L1)-positive and homologous recombination repair mutation subgroups. Treatment-related adverse events (TRAEs) occurred in 93 patients (91%). Grade 3–5 TRAEs occurred in 49 patients (48%). Six deaths (5.9%) were due to adverse events; two (myocardial infarction and unknown cause) were attributed to treatment. Limitations of the study include the single-arm design. Conclusions Pembrolizumab plus olaparib had a safety profile consistent with the profiles of the individual agents and demonstrated antitumor activity in previously treated patients with molecularly unselected, docetaxel-pretreated mCRPC

The concept of spiritual care in mental health nursing

NoIn this paper we aim to clarify the issue of spiritual care in the context of mental health nursing. Background. The concept of spirituality in nursing has received a great deal of attention in recent years. However, despite many articles addressed to the issue, spiritual care remains poorly understood amongst nursing professionals and, as a result, spiritual needs are often neglected within the context of health care. Methods. A series of focus groups was conducted to obtain the views of service users, carers and mental health nursing professionals about the concept of spirituality and the provision of spiritual care in mental health nursing. Results. According to the views expressed in our focus groups, spiritual care relates to the acknowledgement of a person¿s sense of meaning and purpose to life which may, or may not, be expressed through formal religious beliefs and practices. The concept of spiritual care was also associated with the quality of interpersonal care in terms of the expression of love and compassion towards patients. Concerns were expressed that the ethos of mental health nursing and the atmosphere of care provision were becoming less personal, with increasing emphasis on the `mechanics of nursing¿. Conclusions. The perceived failure of service providers to attend adequately to this component of care may be symptomatic of a medical culture in which the more readily observable and measurable elements in care practice have assumed a prominence over the more subjective, deeply personal components. In order for staff to acknowledge these issues it is argued that a more holistic approach to care should be adopted, which would entail multidisciplinary education in spiritual care