Activity and Safety of Crizotinib in Patients with Advanced, Metastatic Alveolar Soft Part Sarcoma (ASPS) with Rearrangement of TFE3: European Organization for Research and Treatment of Cancer (EORTC) Phase 2 Trial 90101 CREATE.

11540 Background: ASPS is an orphan disease associated with rearrangement of transcription factor E3 (TFE3), leading to abnormal MET expression. We assessed crizotinib in pts with ASPS (NCT01524926). Methods: Eligible pts with reference pathology-confirmed ASPS received crizotinib 250 mg bid. By central FISH assessment of TFE3 rearrangement , pts were attributed to MET+ or MET- sub-cohorts. Primary endpoint was objective response rate (ORR; RECIST 1.1) according to local investigator. Secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), progression-free rate (PFR), overall survival rate (OSR), overall survival (OS) and safety. Results: Among 53 consenting pts with confirmed diagnosis of ASPS, 48 were treated and 45 were evaluable. Among 40 MET+ pts, 1 achieved a confirmed partial response (PR) lasting 215 d and 35 had stable disease (SD) (ORR: 2.5%, 95%CI: 0.6-80.6%). Further efficacy endpoints in MET+ cases were: DCR 90.0% (76.3-97.2%); 1-year PFR 37.5% (22.9-52.1%); 1-year OSR 97.4% (82.8-99.6%). Among 4 MET- pts, 1 achieved a PR lasting 801 d and 3 had SD (ORR: 25.0%, 0.6-80.6%) for a DCR of 100% (39.8-100.0%). The 1-year PFR in MET- cases was 50% (5.8-84.5%); 1-year OSR was 75% (12.8-96.1%). One pat with unknown MET status (technical failure) achieved SD but progressed after 17 cycles. Shrinkage of target lesions was seen in 17 pts, both in MET+ and - cases. The most common related AEs were nausea (34/48 [70.8%]), vomiting (22/48 [45.8%]), blurred vision (22/48 [45.8%]), diarrhea (20/48 [41.7%]) and fatigue (19/48 [39.6%]). Conclusions: According to EORTC efficacy criteria for sarcoma, our data suggest that crizotinib has activity in TFE3 rearranged ASPS. While objective responses were infrequent, we observed tumor shrinkage in a significant proportion of pts, excellent DCR and good survival. We present very mature and reliable prospective PFS and OS estimates as reference for future research in pts with ASPS. Clinical trial information: NCT01524926.