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

Abstract

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. The ALK status was assessed centrally using immunohistochemistry and fluorescence in situ hybridisation. The primary end-point was the proportion of patients who achieved an objective response (i.e. complete or partial response). If ≥6 ALK-positive patients achieved a confirmed response, the trial would be deemed successful.

Results: At data cut-off on 28th January 2021, we performed the final analysis of this trial. Of the 20 eligible and treated patients (19 of whom were evaluable for efficacy), with a median follow-up of 50 months, five were still on crizotinib treatment (4/12 ALK-positive and 1/8 ALK-negative patients). The updated objective response rate (ORR) was 66.7% (95% confidence interval [CI] 34.9-90.1%) in ALK-positive patients and 14.3% (95% CI 0.0-57.9%) in ALK-negative patients. In the ALK-positive and ALK-negative patients, the median progression-free survival was 18.0 months (95% CI 4.0-NE) and 14.3 months (95% CI 1.2-31.1), respectively; 3-year overall survival rates were 83.3% (95% CI 48.2-95.6) and 34.3% (95% CI 4.8-68.5). Safety results were consistent with previously reported data.

Conclusion: These updated results confirm previous findings that crizotinib is effective, with durable responses, in patients with locally advanced or metastatic ALK-positive IMT. With further follow-up after the original primary analysis, the ORR increased, as patients derived long-term benefit and some responses converted from stable disease to partial responses.

Clinical trial number: EORTC 90101, NCT01524926.

Keywords: ALK-negative; ALK-positive; Anaplastic lymphoma kinase (ALK) rearrangements; Crizotinib; Inflammatory myofibroblastic tumour (IMT); Locally advanced or metastatic; Tyrosine kinase inhibitor.

Conflict of interest statement

Conflict of interest statement P.S. reports no competing interest related to crizotinib, Pfizer or EORTC, received research support to the institution outside of the scope of this study and reports an advisory or consulting role outside of the scope of this study. M.K., T.S. and A.W. report no competing interest. J-Y.B. reports research support and honoraria from Pfizer outside the scope of this study. S.J.S. received honoraria from Lilly for educational activities. Si.S. reports no competing interest, research support, honoraria and advisory or consulting role outside the scope of this study. P.R. received honoraria from Pfizer outside the scope of this study. V.B., M.G.L., A.I., N.I., M.D-R., R.S., F.S., Ax.N. and An.N. report no competing interest. B.K. reports no competing interest related to crizotinib, Pfizer or EORTC, received research support to the institution outside of the scope of this study and reports an advisory or consulting role outside of the scope of this study.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.