Regorafenib in advanced solitary fibrous tumour: Results from an exploratory phase II clinical study.

Background: To investigate the activity of regorafenib in advanced solitary fibrous tumour (SFT).
Methods: An Italian monocentric investigator-initiated exploratory single-arm Phase II trial was conducted of regorafenib in adult patients with advanced and progressive SFT, until progression or limiting toxicity. Prior treatment with antiangiogenics was allowed. Primary and secondary end-points were: overall response rate (ORR) by Choi criteria, and ORR by RECIST, progression-free survival (PFS), overall survival (OS).
Results: From January 2016 to February 2021, 18 patients were enroled [malignant-SFT = 13; dedifferentiated-SFT (D-SFT) = 4; typical-SFT (T-SFT) = 1]. Fourteen patients were pre-treated, in 12 cases with antiangiogenics (median [m-] lines of treatment = 3). Sixteen patients were evaluable for response (one screening failure; one early discontinuation). Six/16 (35.2%) required a definitive dose reduction. ORR by Choi was 37.5% (95% CI: 15.2-64.6), with 6/16 (37.5%) partial responses (PR), 6/16 (37.5%) stable disease (SD) and 4/16 (25%) progressions; 5/6 responses occurred in patients pre-treated with antiangiogenics. No responses were detected in D-SFT. Best RECIST responses were: 1/16 (6.2%) PR, 12/16 (75%) SD, 3/16 (18.8%) progressions. At 48.4 month m-FU, m-PFS by Choi was 4.7 (inter-quartile range: 2.4-13.1) months, with 31.2% patients progression-free at 1 year.
Conclusion: Regorafenib showed activity in SFT, with 30% patients free-from-progression at one year. Responses were observed also in patients pretreated and refractory to another antiangiogenic agents. However, ORR and m-PFS were lower than reported with other antiangiogenics, and this was possibly due to discrepancies in the patient population and the high-rate of dose reductions.
Competing Interests: Declaration of Competing Interest SS: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: personal financial interests (honoraria, consultancy or advisory role): Aadi, Astex Pharmaceuticals, Bavarian Nordic, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Deciphera, Epizyme, Gentili, GSK, Agenus, Ikena, MaxiVAX, Novartis, PharmaMar, Pharma Essentia, Rain Therapeutics, Servier. Support for attending meetings and/or travel Pharmamar; Institutional financial interests: Advenchen, Bayer, Blueprint, Daiichi Sankyo, Deciphera, Epizyme, Eli Lilly, GSK, Hutchinson, Inhibrx, Karyopharm, Novartis, PharmaMar, Rain Therapeutics, SpringWorks; unpaid Member of the Scientifc Advisory Board of the Chordoma Foundation, Member of the Scientifc Advisory Board of the Desmoid Foundation, Member of the Scientifc Advisory Board of the Epithelioid Hemangioendothelioma Group, Member of the Scientifc Advisory Board of the Leiomyosarcoma Foundation. GGB: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: consulting fees from Eli Lilly, Pharmamar, AboutEvents; honoraria from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai, Istituto Gentili; support for attending meetings and/or travels from Novartis, Pharmamar, Eli Lilly; participation on advisory board from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai. AMF: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: institutional research funding from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Boehriger Ingelheim, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Foghorn Therapeutics Inc., Glaxo, Hutchison MediPharma. Limited, Inhibrx, Inc., Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar, PTC Therapeutics, Rain Oncology, SpringWorks Therapeutics. CM: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: no COIs to declare. FGG: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: no COIs to declare. PC: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: no COIs to declare. MB: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: no COIs to declare. GPD: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: no COIs to declare. NZ: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: institutional research funding from Ikena Oncology, Astex therapeutics. SP: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: institutional research funding from Ikena Oncology, Pharmamar, Astex therapeutics. AG: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: compensations for advisory boards from Novartis, Pfizer, Bayer, Lilly, PharmaMar, SpringWorks, Boehringer Ingelheim; Honoraria from Deciphera; Research grants from PharmaMar and Nanobiotix. PH: Patent patient stratification methods for antiangiogenic agents (Patent number: EPS3665307B1). MI: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: institutional research funding from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Boehriger Ingelheim, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Foghorn Therapeutics Inc., Glaxo, Hutchison MediPharma Limited, Inhibrx, Inc., Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar, PTC Therapeutics, Rain Oncology, SpringWorks Therapeutics. GT: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: no COIs to declare. RM: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: no COIs to declare. PGC: related to the submitted work: Bayer Institutional financial interest; outside the submitted work: institutional research funding from Advenchen Laboratories, Amgen Dompé , AROG Pharmaceuticals, Bayer, Blueprint Medicines, Boehriger Ingelheim, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Foghorn Therapeutics Inc., Glaxo, Hutchison MediPharma Limited, Inhibrx, Inc., Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar, PTC Therapeutics, Rain Oncology, SpringWorks Therapeutics.
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