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Background: Immune checkpoint inhibitors have transformed the treatment landscape of many cancers, including melanoma and renal cell carcinoma (RCC). Randomised trials are evaluating outcomes from reduced ICI treatment schedules with the aim of improving quality of life, tolerability, and cost-effectiveness. This study aims to provide insight into patient and carer's perspectives of these trials., Methods: Seven focus groups were conducted with 31 people with stage IV melanoma, RCC, or caregivers for people receiving ICI. Transcripts were analysed using reflexive thematic analysis., Results: Three themes were generated: 1) "Treatment and clinic visits provide reassurance": reducing hospital visits may not improve quality of life. 2) "Assessment of personal risk versus benefit": the decision to participate in an ICI optimisation trial is influenced by treatment response, experience of toxicity and perceived logistical benefits based on the individual's circumstances. 3) "Pre-existing experience and beliefs about how treatment and trials work", including the belief that more treatment is better, influence views around ICI optimisation trials., Conclusion: This study provides insight into recruitment challenges and recommends strategies to enhance recruitment for ongoing ICI optimisation trials. These findings will influence the design of future ICI optimisation trials ensuring they are acceptable to patients., (© 2024. The Author(s).)

Purpose: Docetaxel and abiraterone acetate plus prednisone or prednisolone (AAP) both improve survival when commenced alongside standard of care (SOC) androgen deprivation therapy in locally advanced or metastatic hormone-sensitive prostate cancer. Thus, patient-reported quality of life (QOL) data may guide treatment choices., Methods: A group of patients within the STAMPEDE trial were contemporaneously enrolled with the possibility of being randomly allocated to receive either docetaxel + SOC or AAP + SOC. A mixed-model assessed QOL in those who had completed at least one QLQ-C30 + PR25 questionnaire. The primary outcome measure was difference in global-QOL (QLQ-C30 Q29&30) between patients allocated to docetaxel + SOC or AAP + SOC over the 2 years after random assignment, with a predefined criterion for clinically meaningful difference of > 4.0 points. Secondary outcome measures included longitudinal comparison of functional domains, pain, and fatigue, plus global-QOL at defined timepoints., Results: Five hundred fifteen patients (173 docetaxel + SOC and 342 AAP + SOC) were included. Baseline characteristics, proportion of missing data, and mean baseline global-QOL scores (docetaxel + SOC 77.8 and AAP + SOC 78.0) were similar. Over the 2 years following random assignment, the mean modeled global-QOL score was +3.9 points (95% CI, +0.5 to +7.2; P = .022) higher in patients allocated to AAP + SOC. Global-QOL was higher for patients allocated to AAP + SOC over the first year (+5.7 points, 95% CI, +3.0 to +8.5; P < .001), particularly at 12 (+7.0 points, 95% CI, +3.0 to +11.0; P = .001) and 24 weeks (+8.3 points, 95% CI, +4.0 to +12.6; P < .001)., Conclusion: Patient-reported QOL was superior for patients allocated to receive AAP + SOC, compared with docetaxel + SOC over a 2-year period, narrowly missing the predefined value for clinical significance. Patients receiving AAP + SOC reported clinically meaningful higher global-QOL scores throughout the first year following random assignment., Competing Interests: Alicia K. MorgansHonoraria: Genentech, Janssen, Sanofi, AstraZeneca, Astellas Scientific and Medical Affairs Inc, Astellas Pharma, Janssen Oncology, Bayer, Janssen, Clovis Oncology, Myovant Sciences, Advanced Accelerator Applications, Exelixis, Pfizer, MerckConsulting or Advisory Role: AstraZeneca, Sanofi, Bayer, Astellas Pharma, Janssen, Advanced Accelerator Applications, Myovant Sciences, Blue Earth Diagnostics, Myovant Sciences, Exelixis, Novartis, Myriad Genetics, Lantheus Medical Imaging, MerckResearch Funding: Bayer, Seattle Genetics/Astellas, Genentech, AstraZeneca, Astellas Scientific and Medical Affairs Inc, Dendreon, Sanofi, Myovant SciencesTravel, Accommodations, Expenses: Sanofi Noel W. ClarkeHonoraria: Janssen-Cilag, Astellas Pharma, Sanofi, Bayer, AstraZeneca, Ferring, IpsenConsulting or Advisory Role: Astellas Pharma, Janssen-Cilag, Ferring, Bayer, SanofiSpeakers' Bureau: Janssen-Cilag, Astellas PharmaResearch Funding: AstrazenecaTravel, Accommodations, Expenses: Janssen-Cilag, Astellas Pharma, Sanofi, Bayer, AstraZeneca, Ferring, Ipsen Gerhardt AttardHonoraria: Astellas Pharma, Janssen (I)Consulting or Advisory Role: Janssen-Cilag, Veridex, Ventana Medical Systems, Astellas Pharma, Medivation, Novartis, Millennium, Abbott Laboratories, ESSA, Bayer, Pfizer, AstraZeneca, FerringSpeakers' Bureau: Janssen, Astellas Pharma, Takeda, Sanofi, Ventana Medical Systems, Ipsen, AstraZeneca, FerringResearch Funding: Janssen, Arno Therapeutics, Innocrin PharmaPatents, Royalties, Other Intellectual Property: I am on The ICR rewards to inventors list of abiraterone acetateTravel, Accommodations, Expenses: Astellas Pharma, Medivation, Ventana Medical Systems, Abbott Laboratories, Bayer, ESSA, Janssen (I), Astellas Pharma (I), Pfizer (I), FerringOther Relationship: Institute of Cancer Research David P. DearnaleyPatents, Royalties, Other Intellectual Property: Abiraterone acetate was developed at The Institute of Cancer Research, which therefore has a commercial interest in the development of this agent. Professor Dearnaley is on the Institute’s Rewards to Inventors list for abiraterone acetate, patent issued EP1933709B1 (location and stabilization device)Travel, Accommodations, Expenses: Janssen Oncology Christopher C. ParkerHonoraria: Bayer, JanssenConsulting or Advisory Role: Clarity Pharmaceuticals, Myovant Sciences, ITM Oncologics Silke GillessenConsulting or Advisory Role: Astellas Pharma (Inst), Janssen (Inst), Bayer (Inst), Orion Pharma GmbH, Tolero Pharmaceuticals (Inst), MSD Oncology (Inst), Roche (Inst), Amgen, Pfizer (Inst), BMS (Inst), Telix Pharma (Inst), MSD Oncology, AAA HealthCare (Inst), Orion Corporation (Inst), Amgen (Inst)Patents, Royalties, Other Intellectual Property: Method for biomarker (WO 3752009138392 A1)Travel, Accommodations, Expenses: ProteoMedixOther Relationship: ProteoMedix, Aranda Pharma (Inst), Menarini Silicon Biosystems (Inst) Christopher D. BrawleyResearch Funding: Astellas Pharma, Clovis Oncology, Janssen, Sanofi/Aventis, Pfizer, Novartis, Jacob S. TanguayConsulting or Advisory Role: AstraZeneca, Astellas Pharma, BayerTravel, Accommodations, Expenses: Janssen, Roche, Bayer Robert J. JonesHonoraria: Astellas Pharma, Janssen, AstraZeneca, MSD Oncology, Bristol Myers Squibb, Pfizer, Novartis, Ipsen, Seattle Genetics, Sanofi, Bayer, Roche/Genentech, EUSA Pharma, Pharmacyclics, Clovis OncologyResearch Funding: Roche, Astellas Pharma, AstraZeneca, Pfizer, Novartis, Exelixis, Clovis Oncology, BayerTravel, Accommodations, Expenses: Ipsen, Bayer, Janssen, Astellas Pharma, MSD John WagstaffHonoraria: Bristol Myers Squibb, Roche, Pierre Fabre, Novartis, GlaxoSmithKline UK Ltd., PfizerConsulting or Advisory Role: Bristol Myers Squibb, Roche, Pfizer, Novartis, Pierre FabreSpeakers' Bureau: Bristol Myers Squibb Sarah RudmanHonoraria: Bristol Myers Squibb Foundation, EUSA Pharma, Ipsen, PfizerConsulting or Advisory Role: Ipsen, Pfizer, EUSA Pharma Joe M. O'SullivanConsulting or Advisory Role: Bayer, Janssen, Astellas Pharma, Sanofi, NovartisSpeakers' Bureau: Bayer, Janssen, NovartisResearch Funding: Bayer Alison BirtleHonoraria: Janssen-CilagConsulting or Advisory Role: Roche, Astellas Medivation, Janssen Oncology, AstraZeneca, Sanofi, Bayer Schering Pharma, Bristol Myers Squib, Merck Serono, PfizerSpeakers' Bureau: Bayer, Janssen Oncology, PfizerResearch Funding: Genzyme Andrew ProtheroeEmployment: Genesis Cancer CareHonoraria: Astellas Pharma, MSD Oncology, Ipsen, Astellas Pharma, Merck Serono, Eisai, MerckTravel, Accommodations, Expenses: Bayer, EUSA Pharma Emma GrayEmployment: Genesis Cancer CareHonoraria: Astellas Pharma, MSD Oncology, Ipsen, Astellas Pharma, Merck Serono, Eisai, MerckTravel, Accommodations, Expenses: Bayer, EUSA Pharma Neil McPhailConsulting or Advisory Role: Eisai, GlaxoSmithKline, IpsenTravel, Accommodations, Expenses: Ipsen Zaf I. MalikConsulting or Advisory Role: Sanofi/Aventis Salil VengalilHonoraria: Bristol Myers Squibb, PfizerConsulting or Advisory Role: Merck/PfizerTravel, Accommodations, Expenses: Ipsen Peter HoskinResearch Funding: Varian Medical Systems, Astellas Pharma, Bayer, Roche, Pfizer, Elekta Matthew R. SydesHonoraria: Lilly, Sanofi, JanssenResearch Funding: Astellas Pharma, Janssen-Cilag, Pfizer, Novartis, Sanofi, Clovis Oncology Simon ChowdhuryHonoraria: Clovis Oncology, NovartisConsulting or Advisory Role: Clovis Oncology, Astellas Pharma, Bayer, Pfizer, Janssen-Cilag, BeiGene, NovartisSpeakers' Bureau: Pfizer, Janssen-CilagResearch Funding: Sanofi/Aventis Mahesh K. B. ParmarResearch Funding: AstraZeneca, Astellas Pharma, Janssen, Clovis Oncology Nicholas D. JamesHonoraria: Sanofi, Bayer, Janssen, Astellas PharmaConsulting or Advisory Role: Sanofi, Bayer, Astellas Pharma, Janssen, Clovis Oncology, EUSA pharma, pfizerSpeakers' Bureau: Pierre Fabre, Ferring, Sanofi, Astellas Pharma, Janssen Oncology, MerckResearch Funding: Janssen, Astellas Pharma, Pfizer, Sanofi, Novartis, AstraZenecaTravel, Accommodations, Expenses: Sanofi, Janssen Ruth E. LangleyConsulting or Advisory Role: Bayer Schering PharmaResearch Funding: Bayer Schering PharmaNo other potential conflicts of interest were reported.

Objectives: To compare quality-of-life (QoL) outcomes at 6 months between men with advanced prostate cancer receiving either transdermal oestradiol (tE2) or luteinising hormone-releasing hormone agonists (LHRHa) for androgen-deprivation therapy (ADT)., Patients and Methods: Men with locally advanced or metastatic prostate cancer participating in an ongoing randomised, multicentre UK trial comparing tE2 versus LHRHa for ADT were enrolled into a QoL sub-study. tE2 was delivered via three or four transcutaneous patches containing oestradiol 100 μg/24 h. LHRHa was administered as per local practice. Patients completed questionnaires based on the European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core (EORTC QLQ-C30) with prostate-specific module QLQ PR25. The primary outcome measure was global QoL score at 6 months, compared between randomised arms., Results: In all, 727 men were enrolled between August 2007 and October 2015 (412 tE2, 315 LHRHa) with QoL questionnaires completed at both baseline and 6 months. Baseline clinical characteristics were similar between arms: median (interquartile range) age of 74 (68-79) years and PSA level of 44 (19-119) ng/mL, and 40% (294/727) had metastatic disease. At 6 months, patients on tE2 reported higher global QoL than those on LHRHa (mean difference +4.2, 95% confidence interval 1.2-7.1; P = 0.006), less fatigue, and improved physical function. Men in the tE2 arm were less likely to experience hot flushes (8% vs 46%), and report a lack of sexual interest (59% vs 74%) and sexual activity, but had higher rates of significant gynaecomastia (37% vs 5%). The higher incidence of hot flushes among LHRHa patients appear to account for both the reduced global QoL and increased fatigue in the LHRHa arm compared to the tE2 arm., Conclusion: Patients receiving tE2 for ADT had better 6-month self-reported QoL outcomes compared to those on LHRHa, but increased likelihood of gynaecomastia. The ongoing trial will evaluate clinical efficacy and longer term QoL. These findings are also potentially relevant for short-term neoadjuvant ADT., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Background: Neoadjuvant chemotherapy before surgery improves survival compared with surgery alone for patients with oesophageal cancer. The OE05 trial assessed whether increasing the duration and intensity of neoadjuvant chemotherapy further improved survival compared with the current standard regimen.Methods: OE05 was an open-label, phase 3, randomised clinical trial. Patients with surgically resectable oesophageal adenocarcinoma classified as stage cT1N1, cT2N1, cT3N0/N1, or cT4N0/N1 were recruited from 72 UK hospitals. Eligibility criteria included WHO performance status 0 or 1, adequate respiratory, cardiac, and liver function, white blood cell count at least 3 × 109 cells per L, platelet count at least 100 × 109 platelets per L, and a glomerular filtration rate at least 60 mL/min. Participants were randomly allocated (1:1) using a computerised minimisation program with a random element and stratified by centre and tumour stage, to receive two cycles of cisplatin and fluorouracil (CF; two 3-weekly cycles of cisplatin [80 mg/m2 intravenously on day 1] and fluorouracil [1 g/m2 per day intravenously on days 1-4]) or four cycles of epirubicin, cisplatin, and capecitabine (ECX; four 3-weekly cycles of epirubicin [50 mg/m2] and cisplatin [60 mg/m2] intravenously on day 1, and capecitabine [1250 mg/m2] daily throughout the four cycles) before surgery, stratified according to centre and clinical disease stage. Neither patients nor study staff were masked to treatment allocation. Two-phase oesophagectomy with two-field (abdomen and thorax) lymphadenectomy was done within 4-6 weeks of completion of chemotherapy. The primary outcome measure was overall survival, and primary and safety analyses were done in the intention-to-treat population. This trial is registered with the ISRCTN registry (number 01852072) and ClinicalTrials.gov (NCT00041262), and is completed.Findings: Between Jan 13, 2005, and Oct 31, 2011, 897 patients were recruited and 451 were assigned to the CF group and 446 to the ECX group. By Nov 14, 2016, 327 (73%) of 451 patients in the CF group and 302 (68%) of 446 in the ECX group had died. Median survival was 23·4 months (95% CI 20·6-26·3) with CF and 26·1 months (22·5-29·7) with ECX (hazard ratio 0·90 (95% CI 0·77-1·05, p=0·19). No unexpected chemotherapy toxicity was seen, and neutropenia was the most commonly reported event (grade 3 or 4 neutropenia: 74 [17%] of 446 patients in the CF group vs 101 [23%] of 441 people in the ECX group). The proportions of patients with postoperative complications (224 [56%] of 398 people for whom data were available in the CF group and 233 [62%] of 374 in the ECX group; p=0·089) were similar between the two groups. One patient in the ECX group died of suspected treatment-related neutropenic sepsis.Interpretation: Four cycles of neoadjuvant ECX compared with two cycles of CF did not increase survival, and cannot be considered standard of care. Our study involved a large number of centres and detailed protocol with comprehensive prospective assessment of health-related quality of life in a patient population confined to people with adenocarcinomas of the oesophagus and gastro-oesophageal junction (Siewert types 1 and 2). Alternative chemotherapy regimens and neoadjuvant chemoradiation are being investigated to improve outcomes for patients with oesophageal carcinoma.Funding: Cancer Research UK and Medical Research Council Clinical Trials Unit at University College London. [ABSTRACT FROM AUTHOR]

Background: Whole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group is poor. We aimed to establish whether WBRT could be omitted without a significant effect on survival or quality of life.Methods: The Quality of Life after Treatment for Brain Metastases (QUARTZ) study is a non-inferiority, phase 3 randomised trial done at 69 UK and three Australian centres. NSCLC patients with brain metastases unsuitable for surgical resection or stereotactic radiotherapy were randomly assigned (1:1) to optimal supportive care (OSC) including dexamethasone plus WBRT (20 Gy in five daily fractions) or OSC alone (including dexamethasone). The dose of dexamethasone was determined by the patients' symptoms and titrated downwards if symptoms improved. Allocation to treatment group was done by a phone call from the hospital to the Medical Research Council Clinical Trials Unit at University College London using a minimisation programme with a random element and stratification by centre, Karnofsky Performance Status (KPS), gender, status of brain metastases, and the status of primary lung cancer. The primary outcome measure was quality-adjusted life-years (QALYs). QALYs were generated from overall survival and patients' weekly completion of the EQ-5D questionnaire. Treatment with OSC alone was considered non-inferior if it was no more than 7 QALY days worse than treatment with WBRT plus OSC, which required 534 patients (80% power, 5% [one-sided] significance level). Analysis was done by intention to treat for all randomly assigned patients. The trial is registered with ISRCTN, number ISRCTN3826061.Findings: Between March 2, 2007, and Aug 29, 2014, 538 patients were recruited from 69 UK and three Australian centres, and were randomly assigned to receive either OSC plus WBRT (269) or OSC alone (269). Baseline characteristics were balanced between groups, and the median age of participants was 66 years (range 38-85). Significantly more episodes of drowsiness, hair loss, nausea, and dry or itchy scalp were reported while patients were receiving WBRT, although there was no evidence of a difference in the rate of serious adverse events between the two groups. There was no evidence of a difference in overall survival (hazard ratio 1·06, 95% CI 0·90-1·26), overall quality of life, or dexamethasone use between the two groups. The difference between the mean QALYs was 4·7 days (46·4 QALY days for the OSC plus WBRT group vs 41·7 QALY days for the OSC group), with two-sided 90% CI of -12·7 to 3·3.Interpretation: Although the primary outcome measure result includes the prespecified non-inferiority margin, the combination of the small difference in QALYs and the absence of a difference in survival and quality of life between the two groups suggests that WBRT provides little additional clinically significant benefit for this patient group.Funding: Cancer Research UK, Medical Research Council Clinical Trials Unit at University College London, and the National Health and Medical Research Council in Australia. [ABSTRACT FROM AUTHOR]