Dementia is a common condition in the UK with around 25% of patients in acute hospitals having dementia. In the UK, there is national guidance on the assessment of cognitive impairment in acute hospitals. This article is a qualitative study of junior doctors' experiences as part of a dementia and delirium team involved in changing the care of patients with dementia in a hospital in the UK. It draws on data from a focus group and follow-up questionnaire in two hospital trusts. We examine what drives doctors to become involved in such projects and the effects of this experience upon them. We suggest a typology for getting junior doctors involved in projects generating change when working with patients with dementia. Being more actively involved in caring for and developing services for patients with dementia may represent the crossing of an educational threshold for these junior doctors.
Indications for immune checkpoint inhibitor therapy are increasing. As the population ages, many patients receiving such drugs will be older adults. Such patients are under-represented in clinical trials, and therefore the safety of immune checkpoint inhibitors in this population has not been adequately assessed. A retrospective multicenter analysis of toxicities was performed in patients with advanced or metastatic solid cancers receiving anti-programmed cell death protein 1 (anti-PD-1) and/or anti-CTLA4 antibodies across three age cohorts (<65 years, 65–74 years and ≥75 years) using univariable and multivariable analyzes. Eligible patients (n=448) were divided into age cohorts: <65 years (n=185), 65–74 years (n=154) and ≥75 years (n=109). Fewer patients in the oldest cohort (7.3%) received an anti-CTLA4 antibody containing regimen compared with the younger cohorts (21.1% and 17.5%). There was no significant difference overall in all grade or ≥G3 toxicities between age cohorts. Significantly fewer patients in the older (65–74 years and ≥75 years) age cohorts discontinued treatment because of toxicity (10.1% and 7.4%) compared with in the <65 years cohort (20.5%; p=0.006). Using logistic regression, only treatment type (ipilimumab containing) was significantly associated with all grade toxicity. However, there was a significantly lower incidence of all-grade endocrine toxicity in the oldest cohort (11.0%) compared with the youngest cohort (22.7%, p=0.02; OR 0.43, 95% CI 0.21 to 0.87), while all-grade dermatological toxicity showed the reverse trend (28.4% vs 18.9%; OR 1.85, 95% CI 1.04 to 3.30). Results were corroborated in the sensitivity analysis using only data from patients who received PD-1 inhibitor monotherapy. This multicenter, real-world cohort demonstrates that immune checkpoint inhibitor therapy is safe and well tolerated regardless of age, with no appreciable increase in adverse events in older adult patients.
9592 Background: ICI responses in UM are rare (~5% with anti-CTLA4/PD1 monotherapy; 10-12% with combination ICI). IMC is a bispecific agent composed of a high affinity T cell receptor targeting the gp100 melanoma antigen fused to an anti-CD3 scFv that increases intratumoral CD8+ T cell infiltration and PD1/PDL1 expression, and may enhance response to post-IMCgp100 ICI. Methods: We previously reported on 19 UM pts treated in the phase I dose escalation cohort of IMC (IMCgp100-102). We performed a retrospective analysis of clinical features and response to pre- and post-IMC ICI for the 12 pts in this cohort as well as 17 other pts (n = 29) treated with post-IMC ICI at 7 centers from 8/2016 to 1/2019. 21/29 pts (including 10/12 pts from IMCgp100-102) are evaluable for response and/or survival and are included in the analysis. Results: Baseline characteristics (n = 21): median age 56 (range 45-69); 57% female; median number of prior therapies 2 (range 1-4). Pre- and post-IMC ICI included: IPI+NIVO (3 pre; 8 post), anti-PD1 monotherapy (7 pre; 8 post), and anti-CTLA4 monotherapy (4 pre; 5 post). 20 pts were evaluable for post-IMC ICI response (1 died before restaging): 3/20 (15%) had partial responses (53-78% regression); 5/20 (25%) had stable disease (SD) > 16 weeks; 1/20 had SD of unknown duration. Median PFS and OS from the initiation of post-IMC ICI were 4.9 (95% CI 2.7-10.7) and 10.1 (95% CI 5.7-NR) months, respectively. 13 pts received pre-IMC ICI, all with eventual disease progression. 3 pts had treatment duration or SD lasting > 6 months. Of these 3 pts, 2 had clinical benefit (defined as objective response or SD > 16 weeks) with post-IMC ICI. There was no clear association between rates of Gr ≥ 2 irAE with pre- or post-IMC ICI and response. For the 10 evaluable pts treated on IMCgp100-102, no marked difference in prior response to IMC (3 SD among 5 ICI responders vs 2 SD among 4 ICI non-responders) or mean tumor shrinkage with IMC (-14.0% vs -18.0%) was observed, but rates of Gr ≥ 2 fever, rash, and/or hypotension with IMC were higher among ICI responders (80% vs 50%). Conclusions: Survival outcomes with post-IMC ICI compare favorably to historical figures in pretreated UM pts. IMC may re-sensitize pts who had prior clinical benefit with ICI to subsequent ICI.
Background The End-of-Life Care (EoLC) Strategy 2008 highlighted the importance of early identification of potential for dying and Advanced Care Planning (ACP).1 2 3 Early awareness of poor prognosis helps patients and their relatives to understand their illness and make informed choices about their care; for instance whether to decline aggressive intervention and hospitalisation if it is unlikely to improve their quality of life. Aims and Objectives To prompt early communication within the MDT and with patients and their relatives about ACP for those deemed to be in their last year of life. Method Data from 40 discharged patients, who had been identified as likely being in their last year of life, was collected in each audit cycle.Cycle 1 was a retrospective case notes analysis from one Care-of-the-Eldery (CoE) ward. Five key areas of ACP were reviewed: resuscitation status, prognosis, ceiling of care, readmission plans, patient/family awareness of condition and prognosis.Prior to cycle 2, an ACP Summary proforma was implemented where discussions around the five key areas could be summarised. It was introduced at a CoE department meeting and teaching sessions were held for junior doctors.Results Tables 1 and 2 illustrate our findings.
In the past 10 years there have been significant advances in the understanding and treatment of metastatic prostate cancer. These include the earlier use of docetaxel chemotherapy, and the use of abiraterone, enzalutamide, radium‐223 and cabazitaxel.1–6 This has led to significant improvements in survival, but has increased the choice and complexity of treatment. In this article, the authors review these advances and look at the sequencing of agents.
e15116 Background: Little data exists for the use of immune checkpoint inhibitors (ICI) in patients ≥80y old. Ageing is associated with immunosenescence, which may impact the efficacy and toxicity of immune-based therapies. Here we provide efficacy and immune related adverse event (irAE) data for patients ≥80y old and younger patient cohorts treated in routine clinical practice at 3 UK Cancer Centres: Guy’s and St Thomas’ NHS Foundation Trust, Oxford University Hospitals NHS Foundation Trust and University Hospitals of Leicester NHS Trust. Methods: Melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) and urothelial carcinoma (UC) patients treated with ICIs between March 2016 – August 2018 were identified, and divided into five age-defined cohorts: < 50y, 50-59y, 60-69y, 70-79y, ≥80y. Median progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method with data censored on 5th February 2018. Frequency and severity of five common irAEs were determined: hepatitis, endocrinopathies, immune-related gastrointestinal, skin and rheumatological. Results: 386 patients aged 22 – 98y (median 67y) received single-agent nivolumab (21%), pembrolizumab (62%), ipilimumab (10%) or combination ipilimumab and nivolumab (7%). 12% of patients were aged < 50y, 18% were 50-59y, 29% were 60-69y, 28% were 70-79y and 13% were ≥80y. Response rates (partial + complete response) were similar across all age groups (53% < 50y, 29% 50-59y, 48% 60-69y, 43% 70-79y and 47% ≥80y). Median PFS was 10.6, 10.3, 10.0, 5.8 and 19.7 months and OS was not reached, not reached, 29.0, 18.3, and 20.9 months for patients < 50y, 50-59y, 60-69y, 70-79y and ≥80y, respectively. The rate of any grade irAEs was lowest in patients ≥80y (59%), and highest in patients < 50y (92%). Grade 3-5 irAEs were also less frequent in patients ≥80y (10%) than those < 50y and 60-69y (both 18%). Conclusions: Of 386 patients 13% were ≥80y with response rates comparable to younger patient cohorts and rates of irAEs lower than younger patient cohorts in this retrospective analysis of a heterogenous patient population. Our data suggests that ICIs are well-tolerated and efficacious in elderly patients and that age alone should not preclude ICI use.
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