larotrectinib
Fuentes regulatorias consultadas
Indicaciones aprobadas
- En adultos y pacientes pediátricos con tumores sólidos que presentan una fusión del gen NTRK, localmente avanzados o metastásicos o cuya cirugía probablemente causaría morbilidad grave, cuando no existen opciones terapéuticas satisfactorias.
Contraindicaciones
Absolutas
- Hipersensibilidad a larotrectinib o a sus excipientes.
Advertencias clínicas
- Advertencia mayor · Puede causar hepatotoxicidad y lesión hepática inducida por fármacos. Controla ALT, AST, fosfatasa alcalina y bilirrubina antes de iniciar, cada 2 semanas durante los primeros 2 meses y después mensualmente; interrumpe, reduce o suspende según gravedad. — DailyMed, VITRAKVI set_id 0c8ca614-58b2-4aa4-83d3-0387a8f782fd
- Advertencia mayor · Puede causar efectos neurológicos centrales, como mareo y alteraciones cognitivas, del ánimo o del sueño. Evita conducir o usar maquinaria si aparecen. — DailyMed, VITRAKVI set_id 0c8ca614-58b2-4aa4-83d3-0387a8f782fd
- Advertencia mayor · Se han notificado fracturas, con mayor incidencia en pediatría. Evalúa dolor o alteraciones de movilidad y maneja según práctica clínica. — DailyMed, VITRAKVI set_id 0c8ca614-58b2-4aa4-83d3-0387a8f782fd
Interacciones medicamentosas
- SeveraInhibidores potentes o moderados de CYP3A, P-gp o BCRP
Mecanismo: Pueden aumentar la exposición a larotrectinib y su toxicidad.
Recomendación: Evita la combinación; si un inhibidor potente de CYP3A es imprescindible, reduce larotrectinib un 50% y vigila toxicidad.
DailyMed, VITRAKVI set_id 0c8ca614-58b2-4aa4-83d3-0387a8f782fdhttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c8ca614-58b2-4aa4-83d3-0387a8f782fd
- SeveraInductores potentes o moderados de CYP3A
Mecanismo: Reducen la exposición y pueden disminuir la eficacia.
Recomendación: Evita la combinación, incluida la hierba de San Juan.
CIMA/AEMPS, ficha técnica VITRAKVI 100 mg, registro 1191385002https://cima.aemps.es/cima/dochtml/ft/1191385002/FT_1191385002.html
- ModeradaSustratos sensibles de CYP3A con margen terapéutico estrecho
Mecanismo: Larotrectinib puede aumentar su exposición.
Recomendación: Evita la combinación; si es imprescindible, vigila estrechamente la toxicidad y coordina el ajuste del sustrato con el equipo prescriptor.
DailyMed, VITRAKVI set_id 0c8ca614-58b2-4aa4-83d3-0387a8f782fdhttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c8ca614-58b2-4aa4-83d3-0387a8f782fd
Eventos adversos
Comunes (≥1%)
ALT elevada · AST elevada · vómitos · anemia · estreñimiento · diarrea · náuseas · fatiga · mareo
Embarazo y lactancia
Puede causar daño embriofetal. Verifica el embarazo antes de iniciar. Las mujeres y los hombres con parejas con capacidad gestante deben usar anticoncepción eficaz durante el tratamiento y al menos 1 mes después; si se usa anticoncepción hormonal sistémica, añade un método de barrera. No amamantes durante el tratamiento; el perfil CIMA exige 3 días después y el perfil FDA, 1 semana después.
Bibliografía reciente (PubMed)
Glioblastoma multiforme (GBM) is a WHO grade 4 glioma and the most common malignant primary brain tumour. Recently, there has been outstanding progress in the treatment of GBM. In addition to the newest form of GBM removal using fluorescence, three-dimensional (3D) imaging, tomoradiotherapy, moderate electro-hyperthermia, and adjuvant temozolomide (post-operative chemotherapy), new developments have been made in the fields of immunology, molecular biology, and virotherapy. An unusual and modern treatment has been created, especially for stage 4 GBM, using the latest therapeutic techniques, including immunotherapy and virotherapy. Modern oncological medicine is producing extraordinary and progressive therapeutic methods. Oncological therapy includes individual analysis of the properties of a tumour and targeted therapy using small-molecule inhibitors. Individualised medicine covers the entire patient (tumour and host) in the context of immunotherapy. An example is individualised multimodal immunotherapy (IMI), which relies on individual immunological tumour-host interactions. In addition, IMI is based on the concept of oncolytic virus-induced immunogenic tumour cell death. In this review, we outline current knowledge of the various available treatment options used in the therapy of GBM including both traditional therapeutic strategy and modern therapies, such as tomotherapy, electro-hyperthermia, and oncolytic virotherapy, which are promising treatment strategies with the potential to improve prognosis in patients with GBM. This newest therapy, immunotherapy combined with virotherapy (oncolytic viruses and cancer vaccines), is displaying encouraging signs for combating GBM. Additionally, the latest 3D imaging is compared to conventional two-dimensional imaging.
Triple-negative breast cancer (TNBC) is associated with high recurrence rates, high incidence of distant metastases, and poor overall survival (OS). Taxane and anthracycline-containing chemotherapy (CT) is currently the main systemic treatment option for TNBC, while platinum-based chemotherapy showed promising results in the neoadjuvant and metastatic settings. An early arising of intrinsic or acquired CT resistance is common and represents the main hurdle for successful TNBC treatment. Numerous mechanisms were uncovered that can lead to the development of chemoresistance. These include cancer stem cells (CSCs) induction after neoadjuvant chemotherapy (NACT), ATP-binding cassette (ABC) transporters, hypoxia and avoidance of apoptosis, single factors such as tyrosine kinase receptors (EGFR, IGFR1), a disintegrin and metalloproteinase 10 (ADAM10), and a few pathological molecular pathways. Some biomarkers capable of predicting resistance to specific chemotherapeutic agents were identified and are expected to be validated in future studies for a more accurate selection of drugs to be employed and for a more tailored approach, both in neoadjuvant and advanced settings. Recently, based on specific biomarkers, some therapies were tailored to TNBC subsets and became available in clinical practice: olaparib and talazoparib for BRCA1/2 germline mutation carriers larotrectinib and entrectinib for neurotrophic tropomyosin receptor kinase (NTRK) gene fusion carriers, and anti-trophoblast cell surface antigen 2 (Trop2) antibody drug conjugate therapy for heavily pretreated metastatic TNBC (mTNBC). Further therapies targeting some pathologic molecular pathways, apoptosis, miRNAS, epidermal growth factor receptor (EGFR), insulin growth factor 1 receptor (IGF-1R), and androgen receptor (AR) are under investigation. Among them, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and EGFR inhibitors as well as antiandrogens showed promisin
Tumor-agnostic, or histology-agnostic, cancer therapy marks a groundbreaking evolution in the realm of precision oncology. In stark contrast to conventional cancer treatments that categorize malignancies based on their tissue of origin (eg, breast, lung, renal cell, etc), tumor-agnostic therapies transcend histologic boundaries, honing in on the genetic and molecular attributes of tumors, regardless of their location. This article offers a comprehensive review of the current landscape of tissue-agnostic cancer therapies and provides clinical insights to empower surgical oncologists with a deeper understanding of these innovative therapeutic approaches.
Advanced cholangiocarcinoma and gene fusions Cholangiocarcinomas (CCAs) are rare digestive tumors classified as intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) CCAs. These tumors are most often diagnosed at an advanced stage, unresectable or metastatic, and associated with a poor prognosis. The identification in recent years of multiple molecular alterations of interest, particularly in iCCA, has nevertheless allowed the development of new targeted therapeutic options for a significant proportion of patients. Gene fusions are among the most frequent alterations, involving FGFR2 in 10-15% of iCCAs in particular, and NTRK genes at a lower frequency (<1%). A dedicated analysis, most often based on RNA sequencing, is required to identify such alterations. Three FGFR inhibitors, pemigatinib, infigratinib and futinatinib, have recently received FDA approval for use in pre-treated patients. These compounds are currently being evaluated as first-line therapy in several phase III trials. Promising results have also been reported with new-generation inhibitors such as RLY-4008, which may soon constitute new therapeutic options. In the case of NTRK fusion, larotrectinib and entrectinib have also demonstrated their efficacy. The objectives of this review are to clarify the specific diagnostic modalities for gene fusions and to summarize the results of the main trials and developments underway for the management of advanced CCA with gene fusions.