ESMO Open

Advances in the treatment of cancer have resulted in improved outcomes for patients, but improving the cure rate is a major unmet need. While testing new anticancer drugs in the earliest settings may be attractive as the chance of benefit may be greatest, it is also a setting where researchers must ensure patients are not harmed, by either over or undertreatment, or denial of timely standard curative treatments. The Methodology for the Development of Innovative Cancer Therapies Taskforce (MDICT) meets immediately before the ESMO-Targeted Anticancer Therapies (ESMO-TAT) meeting, usually held annually in Paris, France, to address questions that are considered important for early academic clinical trials...

BACKGROUND: The number and projections of cancer survivors are necessary to meet the healthcare needs of patients, while data on cure prevalence, that is, the percentage of patients who will not die of cancer by time since diagnosis, are lacking. MATERIALS AND METHODS: Data from Italian cancer registries (duration of registration ranged from 9 to 40 years, with a median of 22 years) covering 47% of the population were used to calculate the limited-duration prevalence, the complete prevalence in 2018, projections to 2030, and cure prevalence, by cancer type, sex, age, and time since diagnosis...

BACKGROUND: Programmed cell death protein 1 (PD-1) inhibitors prolong survival versus chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), which often expresses cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-ligand 1 (PD-L1), providing a rationale for combined PD-(L)1 and CTLA-4 blockade. We report a phase I, open-label study of the PD-L1 inhibitor durvalumab plus the CTLA-4 inhibitor tremelimumab (NCT02262741). METHODS: In dose exploration, two cohorts of previously treated patients received durvalumab 10 mg/kg plus tremelimumab 3 mg/kg, or durvalumab 20 mg/kg plus tremelimumab 1 mg/kg, for up to 12 months...

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No abstract text is available yet for this article.

BACKGROUND: Brigatinib is a next-generation tyrosine kinase inhibitor (TKI) targeting ALK and ROS1. The Barossa study is a multicenter, phase II basket study of brigatinib in patients with ROS1-rearranged solid tumors. ROS1 TKI-naive patients with ROS1-rearranged non-small-cell lung cancer (NSCLC) were enrolled in cohort 1, and ROS1-rearranged NSCLC patients treated previously with crizotinib were enrolled in cohort 2. Patients with ROS1-rearranged solid tumors other than NSCLC were enrolled in cohort 3...

BACKGROUND: Biliary tract cancers (BTCs) exhibit high mortality rates and significant heterogeneity in both clinical and molecular characteristics. This study aims to molecularly characterize a cohort of patients with BTC, with a specific focus on genomic alterations within homologous recombination repair (HRR) genes in a real-world setting. PATIENTS AND METHODS: We carried out a retrospective analysis on 256 patients with BTC treated at five Austrian centers and one German comprehensive cancer center between 2016 and 2023 utilizing comprehensive genomic profiling platforms to assess HRR status and its correlation with clinical outcomes after platinum-based chemotherapy...

Pioneer studies suggested that liver transplantation (LT) has the potential to provide long-term survival in patients with liver-limited metastatic colorectal cancer (mCRC) not amenable for surgery of metastases. Evidence, however, was limited to single-arm studies with few patients enrolled and suboptimal selection criteria, with concerns over access to organ availability overcoming the potential efficacy of LT in this setting. Recently, 5-year survival rates with chemotherapy followed by LT (73%) compared with chemotherapy alone (9%) have been demonstrated by the randomized TransMet trial, enrolling 94 definitively unresectable strictly selected liver-limited mCRC patients...

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) induces direct DNA damage and immunogenic cell death in patients with gastric cancer peritoneal metastases (GCPM). Combining PIPAC-OX with immune checkpoint inhibition remains untested. We conducted a phase I first-in-human trial evaluating the safety and efficacy of PIPAC-OX combined with systemic nivolumab (NCT03172416). METHODS: Patients with GCPM who experienced disease progression on at least first-line systemic therapy were recruited across three centers in Singapore and Belgium...

BACKGROUND: Neoadjuvant chemotherapy is an option for patients with locally advanced rectal cancer at low risk for local recurrence. This randomized phase II trial investigated whether the addition of aflibercept to modified FOLFOX6 (mFOLFOX6) could improve the rates of centrally confirmed pathological complete remissions (pCR) and (disease-free) survival in magnetic resonance imaging (MRI)-staged cT3 rectal cancer. PATIENTS AND METHODS: Patients with rectal cancer fulfilling the following criteria were included: lower border of tumor >5 cm and <16 cm from anal verge; circumferential resection margin >2 mm and T3-tumor with a maximum infiltration of 10 mm, as determined by MRI...

BACKGROUND: Primary mediastinal germ-cell tumors (PMGCTs) account for 1%-3% of all germ-cell tumors (GCTs). Non-seminoma have a poorer prognosis compared to their gonadal counterpart and, according to the International Germ Cell Cancer Collaborative Group, they are considered 'poor risk' disease. Medical treatment is the same, with overall survival (OS) being ∼40%, declining to 10%-15% at 3 years in case of lung and non-visceral metastases. Patients failing first-line chemotherapy have a dismal prognosis, with only 5%-10% of cases being cured in the salvage setting...

BACKGROUND: Poly(ADP-ribose) polymerase inhibitors (PARPis) improved advanced ovarian cancer treatment. Most patients progress during or following PARPi exposure, however, with concerns about sensitivity of subsequent chemotherapy. PATIENTS AND METHODS: In this international cohort study, we evaluated the efficacy of a subsequent chemotherapy following PARPi exposure in high-grade ovarian carcinoma patients. Endpoints included progression-free survival (PFS), overall survival and a multivariable Cox model was built to identify factors influencing PFS...

BACKGROUND: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals with cancer have specific and unique health issues and needs. Reports persist of inequalities in the care provided for these patients, making it important to assess the attitudes and knowledge of LGBTQ needs among those who provide care. MATERIALS AND METHODS: The European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOP Europe) Adolescents and Young Adults Working Group designed this survey comprising 67 questions covering demographics, knowledge, and education of LGBTQ health needs, and attitudes regarding LGBTQ patients with cancer...

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer (BTC), published in late 2022 were adapted in December 2023, according to established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with BTC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with BTC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Taiwan Oncology Society (TOS)...

With the aging population, older adults constitute a growing proportion of the new cancer cases. Given the heterogeneous health status among older adults and their susceptibility to aging-related vulnerabilities, understanding their diversity and its implications becomes increasingly crucial for prognostication and guiding diagnostics, treatment decisions, and follow-up, as well as informing supportive care interventions. Geriatric assessment and management (GAM) refers to the comprehensive evaluation of an older individual's health status with subsequent management plans focusing on both oncologic and non-oncologic interventions...

BACKGROUND: This is a multicentre, single-arm, phase II study aimed at further exploring the activity of trabectedin as second-/further-line treatment in retroperitoneal leiomyosarcoma (LMS) and well-differentiated/dedifferentiated liposarcoma (LPS). MATERIALS AND METHODS: The primary endpoint was the growth modulation index (GMI) defined as the ratio between PFS under trabectedin (PFS) and during previous chemotherapy treatment: time to progression (TTP-1). Secondary endpoints were objective response rate (ORR) and PFS...

BACKGROUND: The introduction of anti-programmed cell death protein 1 (PD-1) immunotherapy has revolutionized the treatment landscape for melanoma, enhancing both response rates and survival outcomes in patients with advanced stages of the disease. Despite these remarkable advances, a noteworthy subset of patients (40%-60%) does not derive advantage from this therapeutic approach. This study aims to identify key predictive factors and create a user-friendly predictive nomogram for stage IV melanoma patients receiving first-line anti-PD-1-based immunotherapy, improving treatment decisions...

BACKGROUND: Mesothelioma is a rare and aggressive malignant neoplasm arising from mesothelial cells, which occasionally manifests recurrent fusions. EWSR1/FUS-CREB, YY1, MAP3K8, NR4A3, and ALK-rearranged proliferations have been reported in limited series with no clear histological or clinical correlations, limiting clinicians' ability to assess prognosis and integrate these new entities into therapeutic decisions. The aim of this study was to better characterize these rearranged proliferations histologically, molecularly, and clinically...

BACKGROUND: The mouse double minute 2 homolog (MDM2) oncogene exerts oncogenic activities in many cancers and represents a potential therapeutic target. This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of alrizomadlin (APG-115), a novel MDM2/p53 inhibitor, in patients with advanced solid tumors. PATIENTS AND METHODS: Patients with histologically confirmed advanced solid tumors who had progressed to standard treatment or lacked effective therapies were recruited...

BACKGROUND: Patients with testicular cancer treated with chemotherapy have an increased risk of developing early cardiovascular events. Identification of patients with testicular cancer at a high risk of these events enables the development of preventative strategies. This study validates the vascular fingerprint tool to identify these patients. PATIENTS AND METHODS: We carried out a multicenter prospective study in patients with metastatic testicular cancer [International Germ Cell Cancer Collaborative Group (IGCCCG) good or intermediate risk; retroperitoneal mass <5 cm]...