The addition of immunotherapy (either atezolizumab or durvalumab) to platinum-etoposide for patients with extensive stage SCLC (ES-SCLC) has been recently established as standard first-line treatment based on IMPOWER133 and CASPIAN trials. Yet, the efficacy and safety in a real-world setting remains unclear.

Background Androgen deprivation therapy (ADT) for prostate cancer (PC) increases fracture risk. In non-cancer populations, FRAX, a fracture risk assessment tool, is used routinely to calculate 10-year probability of major osteoporotic fracture (MOF; spine/hip/forearm/humeral fractures) and hip fracture alone to determine the need for bone density (BMD) assessment and/or treatment. We calculated FRAX using risk factors at entry to the large STAMPEDE PC study. Methods STAMPEDE includes men with newly diagnosed metastatic/high risk non-metastatic PC about to commence ADT, randomised to add or substitute other therapies. Our pre-planned analysis included 6379 men, 86% of enrolment at the time of analysis (2018) for whom FRAX clinical risk factors (excluding femoral neck BMD) were collected prospectively. Secondary osteoporosis in FRAX was set to ‘yes’ for all, as they were about to receive ADT. Glucocorticoid use was set to ‘yes’ for men allocated to abiraterone due to potentially long concomitant use, but not for those allocated shorter treatment with docetaxel. Results Baseline characteristics for this largest dataset of its kind, are shown below. The mean (SD) baseline FRAX 10-year probability was 3.06(2.96)% for hip fracture and 8.70(4.02)% for MOF. Risk increased with increased age at entry, eg MOF probability at age 50-54 years was 4.9% rising to 11.3% in those aged 75 years or older. Using UK National Osteoporosis Guideline Thresholds, 2221 (34.8%) men were classified as high/intermediate risk (meriting BMD scan).The need for BMD assessment varied across planned treatment arms (18.4% in men receiving ADT only to 80.0% in men also planned to receive abiraterone). Table . 857P Characteristic Randomisation years 2006- 2018 Age (y) 67.4±7.2 Height (cm) 174.7±6.9 Weight (kg) 85.6±14.8 BMI (kg/m2) 28.0±4.5 Prevalence of FRAX risk factors (%) Previous fracture after age 50yr 6.1 Glucocorticoid use (≥4 mo) 27.4 Parental hip fracture 7.7 Rheumatoid arthritis 2.4 Alcohol (≥3 units daily) 15.5 Current smoking 11.5 Conclusions FRAX fracture risk assessment in men starting ADT suggests 1 in 3 require BMD assessment to decide on the need for bone protection. Planned treatment in addition to ADT, rather than age, was the main determinant for consideration of bone health. Clinical trial identification 2004-000193-31. Legal entity responsible for the study University of Sheffield. Funding University of Sheffield. Disclosure J.E. Brown: Honoraria (self), Research grant / Funding (institution): Amgen; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self): BMS; Honoraria (self): Daiichi-Sankyo; Honoraria (self): Ipsen; Honoraria (self): Sandoz; Honoraria (self): Merck Sharpe Dome. All other authors have declared no conflicts of interest.

Background Many pts with aGOAC are elderly and/or frail. GO2 [ASCO 2019 #4006] found that lower dose OxaliplatinCapecitabine (OCap) led to non-inferior progression free survival, less toxicity and better patient-centred outcomes using a novel composite endpoint ‘Overall Treatment Utility’. QoL endpoints were chosen to reflect the balance between benefits and harms of the three dose levels and to help patients understand likely implications of treatment for shared decision making. Methods Eligible pts unsuitable for full-dose 3-drug chemotherapy due to frailty, but fit for OCap. Baseline assessment included QoL; symptoms; functional scales; comorbidity; frailty. Randomization was 1:1:1 to dose Level (Lvl) A (Ox 130 mg/m2d1, Cap 625 mg/m2bd d1-21, q21d), B (80% Lvl A doses) or C (60% Lvl A doses) until progression or decision to stop. An alternative randomisation option where chemo benefit was considered uncertain (‘uc’) was between OCap Lvl C and Best Supportive Care (BSC). QoL (EQ-VAS) was measured weekly during chemotherapy. QoL (EQ-5D), Fatigue (EORTC QLQ-C30 Fatigue scale) were measured 9-weekly for 1 year. QoL endpoints were analysed descriptively as pre-defined in the statistical analysis plan. Results 558 pts were enrolled, 2014-17, 61 UK centres, of which 45 pts were in the uc randomisation. Table . LBA46 Lvl A Lvl B Lvl C Lvl C (‘uc’) BSC (‘uc’) Pts 170 171 173 23 22 Median Age 76 76 77 79 79 % PS ≥ 2 31 32 31 57 68 % Severely Frail 61 56 58 70 68 9 wk Δ QLQ QoLa +0.4 +5.3 +4.9 na na 9 wk Δ EQ-5D QoLa -0.01 +0.06 +0.8 -0.19 -0.35 9 wk Δ EQ-VAS QoLa +8.6 +3.4 +5.4 +2.7 +0.2 9 wk Δ Fatigueb +8.6 +3.4 -0.6 +4.0 +15.1 Median TDFc (mths) 7.1 5.4 6.5 na na a. higher=better; b. higher=worse; c. TDF=Time to deterioration in fatigue Longitudinal QoL and Fatigue over the one year follow-up period were very similar between arms. Cancer symptoms also improved to a similar extend in each arm. Conclusions GO2 is the largest RCT to date investigating frail and/or elderly aGOAC pts, and should guide future treatment. Lower doses led to more rapid improvements in QoL and fatigue without compromising disease control or survival. Clinical trial identification EudraCT: 2013-000009-21; ISRCTN44687907 Rec No: 13/YH/0229. Legal entity responsible for the study University of Leeds. Funding Cancer Research UK. Disclosure All authors have declared no conflicts of interest.

Aims: To analyse outcomes in metastatic castrate-resistant prostate cancer (mCRPC) patients treated with radium 223 (Ra-223) across the Yorkshire and Humber Cancer Network. Materials and methods: A regional, multicentre, retrospective cohort study of 189 men undergoing Ra-223 for mCRPC between March 2014 and April 2017 was undertaken. Factors predicting overall survival and completion of planned treatment were assessed. Results: The median overall survival for the entire cohort was 10.5 months. Those completing five to six cycles of Ra-223 had a higher overall survival of 18.6 months. On multivariable analysis, four factors remained independent significant predictors of overall survival: age (P = 0.005, hazard ratio 1.07 [1.02-1.12]); number of cycles of Ra-223: 5-6 versus 1-4 (P <= 0.001, hazard ratio 0.10 [0.005-0.20]); baseline alkaline phosphatase (P = 0.044, hazard ratio 1.06 [1.002-1.12]); neutrophil-to-lymphocyte ratio (P = 0.033, hazard ratio 1.19 [1.01-1.40]). Baseline performance status 0 versus 2 (P = 0.026, odds ratio 0.080 [0.001-0.74]) and higher baseline haemoglobin (P = 0.028, odds ratio 1.04 [1.004-1.074]) were independent predictors of the completion of five to six cycles of Ra-223. Conclusions: Younger age, completion of five to six cycles of Ra-223, lower alkaline phosphatase and neutrophil-to-lymphocyte ratio are predictors of overall survival. This is the first study to report neutrophil-to-lymphocyte ratio as an independent predictor of overall survival in a Ra-223 cohort. Good performance status and higher baseline haemoglobin predict the completion of five to six cycles of Ra-223. Crown Copyright (C) 2018 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. All rights reserved.

Aims: STAR is a randomised phase II/III trial of first-line therapy (sunitinib or pazopanib) comparing a conventional continuation strategy (CCS) to a drug-free interval strategy (DFIS) in the treatment of advanced renal cancer. On transition to phase III a number of important radiology-related protocol alterations were made, which may have a more general application.

Introduction Self-expanding metal stents (SEMS) are an important treatment modality in palliation of malignant dysphagia, either alone or in addition to chemotherapy or radiotherapy. However, the optimal timing of stent insertion remains uncertain when considering prognosis in advanced malignancy. We present a large single centre experience of patients undergoing SEMS insertion for malignant dysphagia. The aim was to identify risk factors associated with overall and 30 day mortality post-oesophageal stenting. Method All patients receiving an oesophageal stent for palliation of dysphagia in primary oesophageal malignancy between January 2009 and December 2013 in Leeds Teaching Hospitals NHS Trust were included. All devices used were Niti S double covered stents inserted by four experienced practitioners using a combined endoscopic and fluoroscopic procedure. Demographics, tumour site and stage, performance status, Charlson co-morbidity index, dysphagia score, previous oncological therapies and serum albumin and CRP in the week prior to stent insertion were retrieved from electronic patient records. Kaplan-Meier survival estimates and Cox proportional hazards regression were performed to identify risk factors predictive of mortality. Results Among 259 patients (mean age 70.3 (range 32 to 99)), the median post-stent survival was 100 days (95% CI, 87 to 116). 51 patients (20%) died within 30 days of the stenting procedure and 10 patients (4%) died within 7 days. 35 patients (14%) required repeat stenting for tumour overgrowth, stricture or stent migration; the median time to re-stent was 137 days (95% CI, 99 to 175). Serum CRP > 50 was an independent predictor of 30 day mortality (hazard ratio [HR], 3.7; 95% CI, 1.7 to 8.0). Overall post-stent mortality was associated with CRP > 50 (HR, 2.3; 95% CI, 1.6 to 3.2) and albumin < 30 (HR, 1.9; 95% CI, 1.1 to 3.1). Conclusion Our 30 day mortality of 20% is consistent with data published elsewhere (131–25%2), but this study identifies the association of elevated CRP with short-term mortality. This may reflect advanced disease or concurrent infection (such as aspiration pneumonia) and may be a useful guide to optimising timing of stent insertion. Disclosure of interest None Declared. References Homs MY, Steyerberg EW, Eijkenboom WM, et al. Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia from oesophageal cancer: multicentre randomised trial. Lancet 2004;364(9444):1497–504 van Heel NC, Haringsma J, Boot H, et al. Comparison of 2 expandable stents for malignant esophageal disease: a randomized controlled trial. Gastrointestinal Endoscopy;76(1):52–8

BACKGROUNDFrailty is a state of vulnerability to poor resolution of homeostasis following a stressor event, such as chemotherapy or cancer surgery. Better knowledge of the epidemiology of frailty could help drive a global cancer care strategy for older people. The aim of this review was to establish the prevalence and outcomes of frailty and pre-frailty in older cancer patients.METHODSObservational studies that reported data on the prevalence and/or outcomes of frailty in older cancer patients with any stage of solid or haematological malignancy were considered. We searched Medline, CINAHL, Cochrane Library, EMBASE, Web of Science, Allied and Complementary medicine, Psychinfo and ProQuest (1 January 1996 to 30 June 2013). The primary outcomes were prevalence of frailty, treatment-related side-effects, unplanned hospitalization and mortality. Risk of bias was assessed using the Newcastle-Ottawa checklist.RESULTSData from 20 studies evaluating 2916 participants are included. The median reported prevalence of frailty and pre-frailty was 42% (range 6%-86%) and 43% (range 13%-79%), respectively. A median of 32% (range 11%-78%) of patients were classified as fit. Frailty was independently associated with increased all-cause mortality [adjusted 5-year hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.36-2.57]. There was evidence of increased risk of postoperative mortality for both frailty (adjusted 30-day HR 2.67, 95% CI 1.08-6.62) and pre-frailty (adjusted HR 2.33, 95% CI 1.20-4.52). Treatment complications were more frequent in those with frailty, including intolerance to cancer treatment (adjusted odds ratio 4.86, 95% CI 2.19-10.78) and postoperative complications (adjusted 30-day HR 3.19, 95% CI 1.68-6.04).CONCLUSIONSMore than half of older cancer patients have pre-frailty or frailty and these patients are at increased risk of chemotherapy intolerance, postoperative complications and mortality. The findings of this review support routine assessment of frailty in older cancer patients to guide treatment decisions, and the development of multidisciplinary geriatric oncology services.

Introduction: Polypharmacy refers to the use of several medications for the treatment or prevention of one or more co-existing diseases. Older oncology patients often have comorbid disorders for which they are taking medication, and may take medication for secondary prevention. The addition of chemotherapy and supportive medications to non-cancer medications increases the risk of drug-related adverse events.

Introduction: The population of elderly patients with cancer is heterogenous. Chronological age alone is a poor predictor of tolerance and outcome from cancer therapy. Comprehensive Geriatric Assessment (CGA) is a process that encompasses somatic, functional and psychosocial domains. It has the potential to be used for prognostication and prediction of benefit from treatment in elderly cancer patients, but may be burdensome to administer. There is a need to define the optimal composition of CGA for each tumour type, and to determine feasibility of administration.

Introduction: Traditional clinical trial endpoints fail to individually capture the balance of benefits and harms from cancer treatments. "Overall Treatment Utility" (OTU) is a novel composite outcome measure that was developed within the FOCUS2 trial in elderly patients treated with chemotherapy for advanced colorectal cancer [1]. It combines clinical and radiological response, toxicity, adverse events and patient-reported acceptability of treatment. OTU needs further development and validation.

Introduction: Advanced gastric and oesophageal cancer typically affects the elderly. Palliative chemotherapy may relieve cancer symptoms and may also extend life-expectancy, but it may also cause side-effects. Establishing the correct balance of benefits and harms in this vulnerable population is critical. Evidence-based chemotherapy consists of intensive multi-drug combinations developed in young fit patients. There is only limited evidence for its use in patients not fit enough to tolerate such regimens. Drug manufacturers and researchers have historically excluded such patients from clinical trials in this type of cancer. There is therefore an urgent need to conduct research that tells us which less-fit people can benefit from, or are harmed by, less intense chemotherapy.

Introduction Many formulae are used to estimate renal function, but none account for the significant variation in creatinine (Cr) measurement between the 26 assays currently used in the UK. The UK National External Quality Assessment Service has published assay-specific Cr adjustors, but the calculated 'standardised Cr' (SCr) dangerously overestimates GFR when used in formulae such as Cockroft and Gault (C&G) and Wright (W). We aimed to develop a simple formula to accurately estimate GFR in oncology patients, using easily available patient characteristics and the SCr, hence accounting for inter-assay variation. Methods Isotopic GFR (iGFR) was measured using Tc99mDTPA clearance. Serum Cr was measured using the O'Leary Jaffe assay and from this SCr derived. Clinical parameters (age, sex, height, weight, SCr, urea and albumin) were used in regression modelling (STATA) to investigate the relationship of individual parameters with iGFR. From this a novel formula was derived to estimate iGFR (the Leeds formula). This formula was then prospectively validated on a second cohort of patients. Results In the discovery set 423 oncology patients were included with a range of malignancies, a median age of 49 (range 18-91) years and serum Cr between 50-130 µmol/l who underwent iGFR measurement between 1/4/06 and 31/3/09. A model incorporating SCr, age, sex, height, weight, urea and albumin predicted iGFR (median calculated GFR 92 ml/ min, range 25-217; r2 of 0.74) more accurately than alternative established GFR formulae e.g. C&G and W formulae (r2 0.4-0.6) . Prospective validation on a separate cohort of oncology patients (496 patients between 1/4/09 and 31/3/11) validated the Leeds formula with an r2 of 0.71 for correlation with iGFR. Conclusions The Leeds formula uses readily available clinical information to estimate GFR more precisely than existing formulae and has the advantage of being applicable to Cr results from any laboratory provided the assay type is known. Many oncologists do not appreciate the resultant effect of inter-Cr assay variability on estimated renal function (GFR) and hence chemotherapy dosing. Disclosure All authors have declared no conflicts of interest.

The National Institutes of Health sponsored a randomized, double-blind, multicenter, placebo-controlled trial of flunarizine (FNR) in epileptic patients receiving concomitant phenytoin (PHT) or carbamazepine (CBZ). Because of FNR's long half-life (up to 7 weeks), a parallel rather than crossover design was used. Each patient received an individualized loading dose and maintenance dosage targeted at a 60-ng/ml plasma FNR concentration. Of 93 patients randomized, 92 provided seizure data for the full 25-week treatment period; one placebo-treated patient dropped out for personal reasons. Fifty-four patients received CBZ only, nine received PHT only, and 30 received both CBZ and PHT. Eighty-seven patients had a history of complex partial seizures, and 60 had secondarily generalized seizures. Eight patients discontinued FNR prematurely, all because of adverse neurologic or psychiatric signs or symptoms; depression was the specific cause in three cases. Calculated maintenance dosages, based on single-dose pharmacokinetic profiles, ranged from 7 to 138 mg/day (mean, 40 mg/day). Plasma FNR concentrations generally exceeded the target, with the highest concentrations observed immediately after loading; excluding the first three treatment weeks and all concentrations after a FNR dosage change, the median plasma FNR concentration was 71.7 ng/ml. The percent reduction from baseline seizure rate was statistically greater (p = 0.002) in the FNR-treated group (mean, 24.4%) than in the placebo-treated group (mean, 5.7%).