Crizotinib may be a safe and effective therapeutic option for patients with transcription factor E3 (TFE3)-rearranged, MET-positive (MET+) alveolar soft part sarcoma (ASPS), according to a study published in the Annals of Oncology.1
For the prospective phase 2 CREATE study (ClinicalTrials.gov Identifier: NCT01524926), researchers administered oral crizotinib 250 mg twice daily to 53 patients with ASPS. Patients were assigned to MET+ or MET- subcohorts depending on whether they had TFE3 rearrangement. Forty-five patients were evaluable at analysis.
Of the 40 patients assigned to the MET+ cohort, 1 patient had a partial response (PR) and 35 patients had stable disease (SD) (overall response rate [ORR], 2.5%; 95% CI, 0.6-80.6%).
Patients in the MET+ cohort had a disease control rate (DCR) of 90% (95% CI, 76.3%-97.2%), a 1-year progression-free survival (PFS) rate of 37.5% (95% CI, 22.9%-52.1%), and a 1-year overall survival (OS) rate of 97.4% (95% CI, 82.8%-99.6%).
Of the 4 patients in the MET– cohort, 1 and 3 patients achieved PR and SD, respectively (ORR, 25.0%; 95% CI, 0.6%-80.6%). The DCR was 100% (95% CI, 39.8%-100.0%), the 1-year PFS rate was 50% (95% CI, 5.8%-84.5%), and the 1-year OS rate was 75% (95% CI, 12.8%-96.1%).
The most frequently reported treatment-related adverse events included nausea, vomiting, diarrhea, blurred vision, and fatigue.
The authors concluded that based on “efficacy criteria for soft tissue sarcoma, our study demonstrated that crizotinib has activity in TFE3 rearranged ASPS MET+ patients.”
- Schoffski P, Wozniak A, Kasper B, et al. Activity and safety of crizotinib in patients with alveolar soft part sarcoma and rearrangement of TFE3. European Organization for Research and Treatment of Canccer (EORTC) phase 2 trial 90101 “CREATE”. Ann Oncol. 2017 Dec 5. doi: 10.1093/annonc/mdx774 [Epub online ahead of print]