Update on clinical research and state of the art management of patients with advanced sarcomas and GIST

Abstract

Sarcomas constitute a rare group of malignancies. According to histology, different treatment options are effective. For gastrointestinal stromal tumours (GISTs), targeted treatment with imatinib controls about 20% of advanced or metastatic disease, whereas chemotherapy is more effective for the rest of the sarcomas. Currently, new targeted treatments are emerging, showing activity in cases resistant to established primary treatment. On the other hand, the exciting results of immunotherapy for other solid tumours, for example, melanoma and lung cancer, make it a promising option in the fight against sarcomas. In this review, we have collected data of established and promising treatments in trials with a view to facilitating the sequencing of sarcoma treatments and for identifying the future of these therapeutic options.

B7-H3 and B7-H4 expression in phyllodes tumors of the breast detected by RNA in situ hybridization and immunohistochemistry: Association with clinicopathological features and T-cell infiltration

“…PD-1/PD-L1 pathway blockade is being rapidly introduced as a therapeutic strategy for several types of cancer, including sarcoma. [9][10][11] Recently, Gatalica et al 5 evaluated PD-1 and PD-L1 expression in 22 malignant PTs including three metastatic tumors. The expression of PD-L1 in tumor tissues was observed in three malignant PT cases (14%) including one metastatic PT.…”

“…7,8 Recent clinical trials have indicated a potential for using immunotherapeutic approaches in patients with sarcomas. [9][10][11] Therefore, we sought to identify targetable immune regulators in PTs of the breast. The interactions between B7 molecules and CD28-family receptors are essential for the regulation of adaptive immunity.…”

Robust Activity of Avapritinib, Potent and Highly Selective Inhibitor of Mutated KIT, in Patient-derived Xenograft Models of Gastrointestinal Stromal Tumors

“…The occurrence of resistance, which is mainly caused by the acquisition of secondary mutations, leads to progression during treatment with imatinib or related compounds. Other small-molecule TKIs, such as sunitinib and regorafenib, are used in patients who are progressing on or are intolerant to imatinib (6). Despite their well-documented clinical activity in imatinibrefractory GIST and their broader activity against a variety of molecular targets, progression on these agents typically occurs after a median treatment duration of less than a year (6).…”

“…Other small-molecule TKIs, such as sunitinib and regorafenib, are used in patients who are progressing on or are intolerant to imatinib (6). Despite their well-documented clinical activity in imatinibrefractory GIST and their broader activity against a variety of molecular targets, progression on these agents typically occurs after a median treatment duration of less than a year (6). To date, there are no established standard treatment alternatives for patients with GIST after failure on all three approved lines of TKI treatment, but a number of compounds are currently being tested in early clinical trials in patients with refractory tumors.…”

Extragastrointestinal Stromal Tumor Presenting as a Recurrent Vaginal Mass: Case Report

“…25,26 Regorafenib is an FDA-suggested third-line therapy drug for GIST patients. 27,28 The second-and third-line treatments do not hold much promise owing to significant side effects and short effective time. 29 Avapritinib (BLU-285, Blueprint Medicines) is a selective KIT inhibitor for the PDGFRA and KIT activation loop mutants.…”