Fusion gene-oriented precision medicine in soft tissue sarcoma
Mené sur 26 patients atteints d’un chondrosarcome myxoïde extrasquelettique de stade avancé (âge médian : 63 ans ; durée médiane de suivi : 27 mois), cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse objective, et la toxicité du pazopanib après échec d'une chimiothérapie de première intention à base d'anthracyclines
Collection of clinical data and development of drugs for rare cancers is difficult because of the small numbers of patients who have the disease. Soft tissue sarcoma is one such rare cancer, which comprises more than 50 histological subtypes. Doxorubicin has been the gold standard drug over the past 30 years because it is the most effective and first choice drug for soft tissue sarcomas in general. The combination of ifosfamide and doxorubicin is the next standard treatment owing to its high toxicity. Gronchi and colleagues introduced a histotype-tailored chemotherapy regimen in the ISG-STS 1001 study to account for probable differences in the efficacy of the standard chemotherapy according to the different histological subtype. Patients were randomly assigned to standard chemotherapy (with epirubicin) versus trabectedin for the treatment of high-grade myxoid liposarcoma, gemcitabine plus dacarbazine for leiomyosarcoma, high-dose ifosfamide for synovial sarcoma, etoposide plus ifosfamide for malignant peripheral nerve sheath tumour, and gemcitabine plus docetaxel for undifferentiated pleomorphic sarcoma. However, none of the histotype-tailored regimens were more efficacious than the standard chemotherapy regimen. Through the development of the first molecular targeted drug in this niche field, pazopanib became the first approved molecular targeted drug for non-adipocytic soft tissue sarcoma, after publication of the results of a randomised, double-blind, placebo-controlled phase 3 trial (PALLETTE). Although oral pazopanib resulted in significant efficacy in progression-free survival compared with placebo, it is more commonly used as a second-line treatment following previous chemotherapy (such as doxorubicin).
The Lancet Oncology 2019