Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors

Abstract Background Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors. Methods Patients with TRK fusion-positive primary CNS tumors from two clinical trials (NCT02637687, NCT02576431) were identified. The primary endpoint was investigator-assessed objective response rate (ORR). Results As of July 2020, 33 patients with TRK fusion-positive CNS tumors were identified (median age: 8.9 years; range: 1.3–79.0). The most common histologies were high-grade glioma (HGG; n = 19) and low-grade glioma (LGG; n = 8). ORR was 30% (95% confidence interval [CI]: 16–49) for all patients. In all patients, the 24-week disease control rate was 73% (95% CI: 54–87). Twenty-three of 28 patients (82%) with measurable disease had tumor shrinkage. The 12-month rates for duration of response, progression-free survival, and overall survival were 75% (95% CI: 45–100), 56% (95% CI: 38–74), and 85% (95% CI: 71–99), respectively. Median time to response was 1.9 months (range 1.0–3.8 months). Duration of treatment ranged from 1.2–31.3+ months. Treatment-related adverse events were reported for 20 patients, with Grade 3–4 in 3 patients. No new safety signals were identified. Conclusions In patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile. </jats:sec

Dementia resources in Argentina: policy, services, and statistics overview-up to date

Argentina, the second largest country in South America, has traditionally been involved in caring for elderly. In 1971 the National Government created the Institute for the Elderly to take care of the social and medical needs of retired people with the program PAMI. This review has updated the local resources of dementia and the challenges that these face with regard to the issues associated with cognitive impairment in elderly people. Health care is shared between the public and private sectors. The distribution of resources and specialists (neurologists, psychiatrist, and geriatricians) is unequal most located in large cities. Facilities for accurate diagnosis are scarce; most of the memory clinics are in big cities like Buenos Aires, Rosario, and Cordoba. Early diagnosis is another challenge with the incorporation of the biomarkers of Alzheimer’s diseases (MRI scan, FDG-PET, amyloid-PET, and Aβ42, tau, and f-tau in cerebrospinal fluid). However the availability is limited to one center in Buenos Aires (FLENI Neurological Institute). ALMA (Association against Alzheimer’s Disease), a member of Alzheimer Disease International, is the local voluntary health organization in Alzheimer’s care and family support. In 2011, the Argentine Neurological Society launched the first dementia guideline for diagnosis and treatment. Although we have a long road ahead, the first steps taken by the organization of a dementia national plan constitute a hopeful challenge.Fil: Bagnati, Pablo Miguel. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; ArgentinaFil: Román, Fabián. Gobierno de la Ciudad Autónoma de Buenos Aires. Ministerio de Salud; ArgentinaFil: Bonafina, Marcela. Clinical and Forensic Neuropsychology; Estados UnidosFil: Blake, Andrew. Gobierno de la Ciudad Autónoma de Buenos Aires. Ministerio de Salud; ArgentinaFil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentin