Metastatic osteosarcoma challenged by regorafenib
Mené en France sur 43 patients adultes atteints d'un ostéosarcome de stade métastatique, cet essai de phase II évalue l'efficacité, du point de vue de la proportion de patients sans progression de la maladie à 8 semaines, et la toxicité du régorafénib après l'échec d'une chimiothérapie de référence
Osteosarcomas belong to a large family of tumour entities of mesenchymal origin which exhibit heterogeneous histological, genetic, and molecular features. Their pathogenesis can be explained by initial TP53 or RB1 somatic alterations, or both, leading to chromosomal instability, followed by secondary oncogenic events and the development of a polyclonal disease associated with the metastatic process. This genetic complexity has been illustrated by a recent series of patients in which investigators have identified a substantial number of point mutations and deletions in an impressive number of genes. It has also stimulated the development of numerous therapeutic strategies targeting tumour cells and their microenvironment. The fact that osteosarcomas are both rare forms of cancer and highly heterogeneous explains why patient survival has not improved in the past four decades, especially for metastatic and unresectable osteosarcomas. Regardless of whether or not the drugs used in the first line of chemotherapy (in neoadjuvant and/or adjuvant chemotherapy for 6–12 months) have been standardised (relatively speaking) and include doxorubicin, cisplatin, methotrexate, and ifosfamide, no consensus has been reached on either the optimum combination or the therapeutic options for patients with recurrent metastatic disease
The Lancet Oncology , commentaire, 2017