BACKGROUND: In patients with metastatic hormone-sensitive prostate cancer (mHSPC), darolutamide significantly improved radiological progression-free survival versus placebo (hazard ratio [HR] 0·54, 95% CI 0·41-0·71) in t...BACKGROUND: In patients with metastatic hormone-sensitive prostate cancer (mHSPC), darolutamide significantly improved radiological progression-free survival versus placebo (hazard ratio [HR] 0·54, 95% CI 0·41-0·71) in the phase 3 ARANOTE study. In addition to survival, symptom control and health-related quality of life (HRQoL) are important factors in treatment decision making; we therefore report pain, HRQoL, and safety outcomes from the ARANOTE trial. METHODS: ARANOTE is an international, randomised, double-blind, placebo-controlled, phase 3 trial involving men aged 18 years or older, with Eastern Cooperative Oncology Group performance status 0-2 and recurrent or de novo mHSPC, treated at 133 cancer centres in 15 countries. Participants were randomly assigned (2:1) to 600 mg darolutamide or matching placebo orally twice daily, both with investigator's choice of androgen deprivation therapy (ADT; luteinising hormone-releasing hormone agonist or antagonist, or orchiectomy) starting within 12 weeks before randomisation. Randomisation was stratified by presence versus absence of visceral metastases and by previous versus no previous local therapy. Treatment was assigned centrally using an interactive web response system based on a computer-generated permuted block randomisation list with block sizes of six. The investigators, the participants, and the sponsor remained masked to treatment assignment throughout the study. The primary endpoint (reported previously) was radiological progression-free survival. Here, we assessed time to pain progression (≥2-point increase in Brief Pain Inventory-Short Form worst pain score or initiation of opioid for ≥7 days; secondary endpoint) and time to deterioration of overall wellbeing (≥10-point decrease in Functional Assessment of Cancer Therapy-Prostate [FACT-P] total score; prespecified exploratory endpoint). Pain and HRQoL outcomes were analysed in the intention to treat population; safety was analysed in all treated patients according to treatment actually received. The trial, registered at ClinicalTrials.gov, NCT04736199, is ongoing, but no longer recruiting. FINDINGS: Between Feb 23, 2021, and June 14, 2022, 669 patients (all male; 376 [56%] White, 209 [31%] Asian, 65 [10%] Black, 19 [3%] other race) were randomly assigned to receive darolutamide (n=446) or placebo (n=223). At the data cutoff date for the primary analysis (June 7, 2024), the median follow-up duration for the analyses presented here was 22·8 months (IQR 12·3-27·4) in the darolutamide group and 20·3 months (11·4-25·2) in the placebo group. Darolutamide delayed time to pain progression (HR 0·72; 95% CI 0·54-0·96) and extended time to deterioration in FACT-P total score (HR 0·76; 0·61-0·94) versus placebo. The most common grade 3-4 adverse events were hypertension (19 [4%] of 445 patients who received darolutamide vs eight [4%] of 221 patients who received placebo), anaemia (14 [3%] vs eight [4%]), and aspartate aminotransferase increase (ten [2%] vs one [<1%]). Serious adverse events occurred in 105 (24%) versus 52 (24%) patients, respectively. One treatment-related grade 5 event occurred, reported as death (not otherwise specified). INTERPRETATION: Along with the known survival benefits, the clinically meaningful delays in pain progression and time to deterioration of overall wellbeing support consideration of darolutamide plus ADT as a standard-of-care treatment option in patients with mHSPC. FUNDING: Bayer and Orion Pharma.
Persistent inequities in cancer outcomes remain a defining challenge for global health systems, including in high-income countries. Despite advances across prevention, early detection, treatment, and survivorship, dispar...Persistent inequities in cancer outcomes remain a defining challenge for global health systems, including in high-income countries. Despite advances across prevention, early detection, treatment, and survivorship, disparities persist, reflecting entrenched social and structural inequities. While equity is increasingly articulated within national and global cancer agendas, comparative analysis of how equity is conceptualised and operationalised in national cancer control planning remains limited. This Policy Review addresses this gap by synthesising evidence across seven high-income countries comprising the G7 Cancer collaboration-Australia, Canada, France, Germany, Japan, the UK, and the USA-drawing on policy frameworks, National Cancer Control Plans (NCCPs), and semi-structured expert interviews. The Policy Review identifies marked variation in equity definitions and application, with most countries emphasising access to care, fewer addressing outcomes or patient experience, and equity often being framed as secondary to broader health system goals. Terminology is inconsistently applied and action on structural determinants is limited. Barriers to NCCP implementation encompass fragmented accountability, restricted policy mandates, and fiscal or cultural sensitivities. Enablers of effective NCCP implementation include data infrastructure systems, multistakeholder engagement, legislative frameworks, and cross-sector collaboration. Synthesising these findings, we present an evidence-informed Policy Framework for Equity in Cancer Control, to guide equitable cancer policy in high-income settings.
Mellinghoff SC, Liss B, Stemler J
… +17 more, Petzer V, Egger-Heidrich K, Monin MB, Christopeit M, Giesen N, Keppler-Hafkemeyer A, Hattenhauer T, Heinz WJ, Khatamzas E, Maschmeyer G, Mispelbaum R, Steinke J, Richardson T, Sprute R, Cornely OA, Rieger CT, German Society of Hematology and Medical Oncology Infectious Diseases Working Group (AGIHO)
Vaccine-preventable infections remain a major cause of morbidity and mortality in patients with cancer. The updated guideline for anti-infective vaccination strategies in patients with cancer of the German Society of Hem...Vaccine-preventable infections remain a major cause of morbidity and mortality in patients with cancer. The updated guideline for anti-infective vaccination strategies in patients with cancer of the German Society of Hematology and Medical Oncology Infectious Diseases Working Group was developed by a guideline panel of experts in internal medicine, haematology, medical oncology, and infectious diseases. For previously covered vaccinations, we included all publications in patients with cancer starting from 2017, as this was the data cutoff for the previous guideline, and for newly included vaccines all publications were reviewed. After data extraction and critical discussion, the recommendations were graded following a standardised international grading system. This update introduces general recommendations, optimal vaccination timing, potential use of live vaccines, and immunisation of close contacts and household members of patients. Moreover, specific sections for patients with solid tumours and patients with haematological malignancies have been introduced. Guidance has been added for patients receiving novel therapies such as tyrosine kinase inhibitors, bispecific antibodies, and chimeric antigen receptor T cells. This guideline addresses the urgent medical need to reduce vaccine-preventable diseases and aims to improve vaccination uptake among patients with cancer and their caregivers.
Bhatt A, Stepanyan A, Al-Niaimi A
… +22 more, Brennan D, Baumgartner J, Bakrin N, Chi D, Deraco M, Ferron G, Fotopoulou C, Kepenekian V, Kusamura S, Lavoue V, Moran B, Planchamp F, Arjona-Sanchez A, Sehouli J, Sukumar V, Turaga K, Villeneuve L, Van Der Speeten K, Van Driel W, Eriksson AGZ, Zapardiel I, Glehen O
Complete macroscopic resection is the key objective of cytoreductive surgery for peritoneal malignancy. However, heterogeneity in terminology and operative technique persists across centres and between surgical and gynae...Complete macroscopic resection is the key objective of cytoreductive surgery for peritoneal malignancy. However, heterogeneity in terminology and operative technique persists across centres and between surgical and gynaecological disciplines. This study sought to establish international consensus on the nomenclature of cytoreductive surgery procedures, key technical principles of peritonectomy procedures and visceral resections, and management of regional lymph nodes in the context of peritoneal malignancy. A modified Delphi process was undertaken involving 148 surgical and gynaecological oncologists across six continents. Cytoreductive surgery was endorsed as the preferred term for potentially curative surgery for peritoneal malignancy. Agreement was reached on core principles guiding peritonectomy, including the extent of peritoneal resection around tumour deposits. For visceral resections, the panel favoured a conservative, tumour biology-informed strategy that considers disease distribution and patient-specific factors. The group recommended selective removal of clinically enlarged nodes only. This global consensus defines foundational principles for cytoreductive surgery in patients with peritoneal malignancy and provides standardised terminology and operative guidance that can be integrated into routine surgical practice across various surgical oncology disciplines. Adoption of these recommendations has the potential to reduce variability in cytoreductive surgery techniques, facilitate comparison between studies by increasing standardisation, and facilitate the design and conduct of high-quality surgical trials in peritoneal malignancy.