Latest news with #multicentre
Medscape
21-07-2025
- Health
- Medscape
TNT Shows Similar Efficacy Across Regimens in Rectal Cancer
TOPLINE: In a multicentre study of patients with locally advanced rectal cancer, substantial variation existed in the choice of total neoadjuvant therapy (TNT), but efficacy was comparable across different regimens and consistent with that reported in clinical trials. METHODOLOGY: Researchers conducted an international, multicentre study in 21 countries and included 1585 patients (median age, 61 years; 37.1% women) with stage II/III rectal adenocarcinoma from September 2012 to December 2023. The primary objective focused on the type of TNT administered depending on the regimen, timing and type of chemotherapy, and type of radiotherapy. Secondary objectives encompassed safety and efficacy overall and on the basis of the type of TNT after propensity vector matching. Efficacy endpoints included pathologic complete response, complete response, local or distant progression at the time of treatment failure, event-free survival (EFS), and overall survival (OS). Overall, 17.7%, 33.4%, 12%, and 16.2% of patients were treated according to PRODIGE 23-like, RAPIDO-like, OPRA induction-like, and OPRA consolidation-like regimens, respectively. TAKEAWAY: Chemotherapy was given as induction, consolidation, and sandwich for 34.5%, 51.0%, and 14.5% of patients, respectively; regimens were single agent (1.1%), doublet (78.8%), and triplet (20.1%). Radiotherapy was delivered as short-course radiotherapy in 37.2% and long-course chemoradiotherapy in 62.8% of cases. The pathologic complete response rate was 21.3%, and the complete response rate was 23.2%; local and distant progression at the time of treatment failure were 7% and 16.2%, respectively. Three-year EFS reached 68%, and 5-year OS was 79%. In the overall population, PRODIGE 23-like regimens showed better survival outcomes than RAPIDO-like regimens (EFS: hazard ratio [HR], 0.68; P = .03; OS: HR, 0.51; P = .04), OPRA induction-like regimens (EFS: HR, 0.66; P = .04; OS: HR, 0.35; P = .003), and OPRA consolidation-like regimens (EFS: HR, 0.64; P = .02; OS: HR, 0.50; P = .05). After the propensity vector matching analysis of 928 patients (58.5%), no significant differences in survival outcomes were observed between TNT regimens. IN PRACTICE: "This case series study illuminates the applicability of TNT to clinical practice," the authors of the study wrote. "TNT decisions should be made based on the individual risk profile and following an accurate discussion about the positives and negatives of each option while considering patient preferences and expectations," they added. SOURCE: This study was led by Alessandro Audisio, MD, Université libre de Bruxelles, Institut Jules Bordet-Hôpital Erasme, Brussels, Belgium. It was published online on July 10, 2025, in JAMA Oncology. LIMITATIONS: The retrospective design of the study introduced potential data collection errors and biases, which were only partially addressed through remote monitoring and data imputation. The relatively short follow-up period may have prevented the detection of differences in long-term outcomes between TNT regimens. Additionally, variations in treatment delivery, staging methods, and supportive care across institutions complicated direct comparisons. Despite involving multiple countries, the predominant European patient population limited the generalisability of the results. DISCLOSURES: This study was sponsored by the Institut Jules Bordet and endorsed by the Oncodistinct Network. Several authors reported receiving personal fees and grants and having other ties with various sources. Additional disclosures are noted in the original article. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Yahoo
14-07-2025
- Health
- Yahoo
Verastem's avutometinib combination shows 31% ORR in ovarian cancer trial
Verastem Oncology has reported primary analysis data from the two-part multicentre Phase II RAMP 201 trial, demonstrating that avutometinib plus defactinib showed a confirmed overall response rate (ORR) of 31% in treating recurrent low-grade serous ovarian cancer (LGSOC) patients. The analysis was published in the Journal of Clinical Oncology (JCO). The parallel cohort, adaptive, open-label, randomised study assessed avutometinib alone and in conjunction with defactinib in those with recurrent LGSOC. These patients had undergone a median of three previous therapy lines, including hormonal therapy, chemotherapy, bevacizumab, and MEK inhibitors. Part A of the trial determined the choice of the go-forward regimen, which was the combination therapy against avutometinib alone, based on ORRs. Parts B and C, the trial's expansion phases, assessed the safety and efficacy of the go-forward regimen of 3.2mg of avutometinib bi-weekly, and 200mg of defactinib twice a day. Part D of the trial assessed a low dose of the combination to inform the reduction of the individualised dose. The data published stated that the combination resulted in an ORR of 31% in 109 evaluable subjects in the trial. The response rate was also higher in those with a KRAS mutation, at 44%, compared to 17% in KRAS wild-type patients. The median duration of response (DOR) was reported to be 31.1 months across all subjects, with similar results seen in the KRAS mutant population. Despite this, the KRAS wild-type population had a shorter median DOR of 9.2 months. Median progression-free survival (PFS) was 12.9 months for all subjects, extending to 22 months in the KRAS mutant population and 12.8 months in the KRAS wild-type population. The disease control rate (DCR) at six months or more was 61% in the total population, with a higher rate of 70% in the KRAS-mutated group and 50% in the KRAS wild-type group. Most patients, regardless of KRAS mutation status, experienced some minimisations in target lesions. Last year, Verastem announced the dosing of the first subject with GFH375/VS-7375 as part of a Phase I/II trial in China. "Verastem's avutometinib combination shows 31% ORR in ovarian cancer trial" was originally created and published by Clinical Trials Arena, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site. Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Medscape
14-07-2025
- Health
- Medscape
Lurbinectedin Shows Modest Efficacy and Safety in ES-SCLC
TOPLINE: In a multicentre study, lurbinectedin demonstrated a favourable safety profile and consistent efficacy and may be considered for compassionate use in patients with extensive-stage small cell lung cancer (ES-SCLC). However, poor performance status, a chemotherapy-free interval of less than 90 days, and the presence of brain or liver metastases may have negatively affected overall survival (OS). METHODOLOGY: This multicentric, international cohort included 238 adult patients with ES-SCLC (median age, 65 years) who received lurbinectedin intravenously at 3.2 mg/m 2 every 3 weeks as second- or further-line treatment between November 2019 and September 2024. every 3 weeks as second- or further-line treatment between November 2019 and September 2024. The primary objective was to assess the effectiveness of lurbinectedin with regard to objective response rate, disease control rate, duration of response, progression-free survival (PFS), and OS and its safety profile. The median follow-up duration was 5.53 months. TAKEAWAY: Overall, 37% of patients received lurbinectedin as second-line therapy, 45% received it as third-line therapy, and 18% received it as further-line therapy. The objective response rate was 23.1%, and the disease control rate was 45.4%. The median PFS was 2.2 months, and the median OS was 5.4 months. The 6-month PFS and OS rates were 12.2% and 42.4%, respectively. Patients with a chemotherapy-free interval of 90 days or more showed significantly longer PFS (3.1 vs 1.8 months; hazard ratio [HR], 0.46; P < .001) and OS (6.8 vs 4.5 months; HR, 0.56; P = .006) than chemoresistant patients. Eastern Cooperative Oncology Group performance status of two or more at treatment start and the presence of brain or liver metastases were associated with worse outcomes. Treatment-related adverse events (AEs) of any grade were recorded in 92% of patients, with 29% of patients experiencing at least one grade 3-4 toxicity and the most frequent being neutropenia that occurred in 22% of patients. IN PRACTICE: "Our study provides valuable real-world insights into the effectiveness and safety of lurbinectedin as compassionate use treatment for ES-SCLC, supporting its use with outcomes consistent with those observed in clinical trials and other real-world studies. However, the outcomes for patients with poor PS [performance status] at lurbinectedin start, a CFI [chemotherapy-free interval] of less than 90 days, and brain or liver metastases remain suboptimal and this should be carefully considered when making treatment decisions," the authors of the study wrote. SOURCE: This study was led by Daniela Scattolin, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy. It was published online on July 02, 2025, in the European Journal of Cancer. LIMITATIONS: This study was limited by its retrospective design, the small number of participating centres, and imbalanced cohort sizes between countries. Researchers noted heterogeneity in baseline patient characteristics, treatment management strategies, and tumour assessment protocols. Additionally, differences in national regulations regarding chemoimmunotherapy use could have introduced bias. The retrospective nature of data collection may have resulted in underreporting of AEs. DISCLOSURES: This study did not receive any specific funding. Several authors reported receiving speaker/consultant fees and having other ties with various sources. Additional disclosures are noted in the original article. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
07-07-2025
- Health
- Medscape
Delayed Breast Cancer Care Raises Mortality Risk
TOPLINE: Patient-attributable delays exceeding 90 days in breast cancer care were associated with a more than threefold higher risk for 2-year mortality. Living alone emerged as the only independent predictor of prolonged patient-attributable delay (PPAD), increasing the risk for delay by 88.2%. METHODOLOGY: This multicentre prospective cohort study included 543 symptomatic patients with breast cancer diagnosed between 2013 and 2015 across 10 hospitals in Spain's National Health System. PPAD was defined as a delay of more than 90 days between symptom onset and the first medical consultation; overall, 77 patients experienced a PPAD. Researchers examined associations between PPADs and clinical outcomes, including 2-year mortality, while considering sociodemographic and clinical-pathological factors. Diagnosis confirmation involved imaging techniques, including mammography and/or ultrasound, followed by biopsy. TAKEAWAY: Living alone emerged as the sole independent predictor of PPAD (odds ratio [OR], 1.882; 95% CI, 1.033-3.42; P = .039). Among patients who sought medical care within 90 days, the mortality rate was 3.2%; however, among those who experienced delays exceeding 90 days, the rate was 11.7%. In multivariate analysis, patient-attributable delays exceeding 90 days remained a significant risk factor for 2-year mortality (OR, 3.08; 95% CI, 1.05-9.07), and advanced disease stages (stages III-IV) demonstrated the highest risk for mortality (OR, 6.78; 95% CI, 2.51-18.3). Age remained a significant predictor of mortality (OR, 1.04; 95% CI, 1.01-1.07). The basal-like immunophenotype demonstrated the highest risk for mortality among subtypes (OR, 7.49; 95% CI, 2.68-20.9). IN PRACTICE: "Our findings highlight the need for targeted interventions to raise cancer symptom awareness and address barriers faced by vulnerable groups, such as the elderly and individuals living alone, to reduce delays, improve clinical outcomes, increase survival rates, and ultimately the quality of life for patients," the authors of the study wrote. SOURCE: This study was led by Desirée Martín-García, Hospital Universitario Costa del Sol, Marbella, Spain. It was published online on June 24, 2025, in the European Journal of Surgical Oncology. LIMITATIONS: Psychosocial factors that contributed to delayed medical attention were not collected as part of the original study protocol, which limited the ability to fully understand patient motivations. This study relied on self-reported data regarding the time patients take to seek medical care, which may have introduced recall bias. Additionally, the study's focus on the Spanish healthcare context may have limited the generalisability of the findings to other settings with different healthcare systems and cultural dynamics. DISCLOSURES: This study received funding from the Carlos III Health Institute and Andalusian Ministry of Health, with co-funding from the European Social Fund/European Regional Development Fund. The authors declared having no conflicts of interest. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
18-06-2025
- Health
- Medscape
Comorbidities Intensify Rare Neurologic Diseases
Comorbidities, especially cardiovascular and autoimmune diseases, were frequent in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), correlating with worse clinical outcomes, including more frequent optic neuritis relapses, greater disability, and retinal layer thinning. METHODOLOGY: The CROCTINO study was a retrospective, multicentre cohort study that analysed data of 442 patients with AQP4-NMOSD, MOGAD, and double seronegative NMOSD (DN-NMOSD) across 22 centres worldwide between 2000 and 2018, focusing on retinal pathology using optical coherence tomography (OCT). Researchers assessed comorbidities (classified into 14 categories) and their impact on disease severity, optic neuritis relapse rates, Expanded Disability Status Scale (EDSS) scores, and retinal integrity using OCT. They compared the prevalence and types of comorbidities across disease groups, evaluated associations with clinical outcomes, and analysed changes in retinal layer thickness. TAKEAWAY: Comorbidities were present in 43.5% of patients with AQP4-NMOSD, 40.8% of those with MOGAD, and 36.4% of those with DN-NMOSD. Those with AQP4-NMOSD had more multiple comorbidities than those with MOGAD (50% vs 25%; P = .03). = .03). EDSS scores were higher in patients with MOGAD and comorbidities than in those without (3.0 vs 2.0; P = .006) and in those with DN-NMOSD and comorbidities than in those without (5.0 vs 2.0; P = .008), but not significantly different between those with AQP4-NMOSD and those without. = .006) and in those with DN-NMOSD and comorbidities than in those without (5.0 vs 2.0; = .008), but not significantly different between those with AQP4-NMOSD and those without. Among patients with AQP4-NMOSD, those with cardiovascular comorbidities exhibited higher annual optic neuritis relapses than those with autoimmune comorbidities (mean, 1.06 ± 3.33 vs 0.49 ± 0.98; P < .001). < .001). Retinal changes showed reduced inner nuclear layer thickness in patients with AQP4-NMOSD having comorbidities, especially cardiovascular conditions ( P = .009). IN PRACTICE: "Comorbidities are frequent in AQP4-NMOSD and MOGAD and are associated with ON [optic neuritis] frequency and disability. These findings highlight the need for proactive comorbidity management to improve patient care," the authors wrote. SOURCE: This study, led by Sara Samadzadeh, Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark, was published online on June 09, 2025, in the European Journal of Neurology . LIMITATIONS: This study's retrospective design may have led to inaccuracies in comorbidity documentation, including unrecorded risk factors (eg, smoking) and inconsistent data recorded. Some comorbidities could independently affect OCT or EDSS outcomes, potentially confounding the results. DISCLOSURES: This study was supported by the Lundbeck Foundation; the University of Southern Denmark, Slagelse Hospital Research Fund, and Region Zealand Health Sciences Research Fund; and the Guthy-Jackson Charitable Foundation. Some authors reported receiving support from several other organisations.
