Exploratory analysis of tumor imaging in a Phase 2 trial with cabozantinib in gastrointestinal stromal tumor: lessons learned from study EORTC STBSG 1317 'CaboGIST'.

Background: Gastrointestinal stromal tumors (GISTs) are malignant mesenchymal tumors arising in the gastrointestinal tract. Their systemic treatment is based on the use of tyrosine kinase inhibitors (TKIs) with imatinib, sunitinib, and regorafenib being the preferred agents. Assessment of tumor response to TKI treatment in GISTs is traditionally done according the Response Evaluation Criteria in Solid Tumors (RECIST), while Choi criteria have also been proposed as alternative tool assessing both volumetric and density changes on computer tomography (CT) scans.

Long-term efficacy update of crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumour from EORTC trial 90101 CREATE.

Purpose: European Organisation for Research and Treatment of Cancer (EORTC) 90101 (CREATE) was a prospective, multicentric, non-randomised, open-label phase II basket trial to assess the efficacy and safety of crizotinib in patients with different types of cancers, including advanced inflammatory myofibroblastic tumour (IMT) with or without anaplastic lymphoma kinase (ALK) rearrangements. Here, we report updated results with long-term follow-up.

Patients/methods: After central reference pathology, eligible ALK-positive and ALK-negative patients with advanced/metastatic IMT deemed incurable with surgery, radiotherapy or systemic therapy received oral crizotinib 250 mg twice daily.

Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 'CaboGIST'.

Background: Gastrointestinal stromal tumour (GIST) is commonly treated with tyrosine kinase inhibitors (TKIs), but most patients ultimately develop secondary resistance. Cabozantinib, a multi-targeted TKI inhibitor, has activity in patient-derived GIST mouse xenograft models and can overcome compensatory MET signalling occurring on TKI treatment. European Organisation for Treatment of Cancer (EORTC) 1317 'CaboGIST' assessed the safety and activity of cabozantinib in patients with GIST who had progressed on imatinib and sunitinib.

Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumours with and without anaplastic lymphoma kinase gene alterations (European Organisation for Research and Treatment of Cancer 90101 CREATE): a multicentre, single-drug, prospective, non-randomised phase 2 trial.

Background: An inflammatory myofibroblastic tumour (IMFT) is a rare mesenchymal neoplasm characterised by anaplastic lymphoma kinase (ALK) gene rearrangements. We assessed the activity and safety of crizotinib, a tyrosine kinase inhibitor, targeting ALK in patients with advanced IMFT either with or without ALK alterations.

Methods: We did a multicentre, biomarker-driven, single-drug, non-randomised, open-label, two-stage phase 2 trial (European Organisation for Research and Treatment of Cancer 90101 CREATE) at 13 study sites (five university hospitals and eight specialty clinics) in eight European countries (Belgium, France, Germany, Italy, Netherlands, Poland, Slovakia, and the UK).

The tyrosine kinase inhibitor crizotinib does not have clinically meaningful activity in heavily pre-treated patients with advanced alveolar rhabdomyosarcoma with FOXO rearrangement: European Organisation for Research and Treatment of Cancer phase 2 trial 90101 'CREATE'.

Background: Alveolar rhabdomyosarcomas (ARMSs) can harbour MET and anaplastic lymphoma kinase (ALK) alterations. We prospectively assessed crizotinib in patients with advanced/metastatic ARMS.

Methods: Eligible patients with a central diagnosis of ARMS received oral crizotinib 250 mg twice daily.

Identification of microRNA biomarkers for response of advanced soft tissue sarcomas to eribulin: Translational results of the EORTC 62052 trial.

Background: Recent phase II and III clinical trials demonstrated anti-tumour activity of eribulin, a tubulin-interacting cytotoxic agent, in patients with metastatic soft tissue sarcoma (STS). In this exploratory study, we aimed to identify putative microRNA biomarkers that associate with eribulin sensitivity or resistance in STS.

Materials And Methods: Archival tumour tissue from primary tumours or metastatic lesions was collected prior to eribulin treatment, from 65 consenting patients involved in the EORTC trial 62052.