Abstract 1951P
Background
Angiosarcoma is a rare and aggressive cancer of the endothelial cells. It has been shown that β-adrenergic signaling through the β-adrenoceptors (ADRB) 1 and 2, that are overexpressed in angiosarcoma, promotes tumor growth. Propranolol, a non-selective β-blocker, was able to initiate apoptosis in angiosarcoma cell lines and its anti-tumor activity has been demonstrated in several case reports. The aim of this window-of opportunity trial was to prospectively evaluate the anti-tumor activity of propranolol in patients with angiosarcoma.
Methods
Patients with angiosarcoma with a waiting time of 3 to 6 weeks until start of standard treatment were eligible. Propranolol was dosed 80 mg to 240 mg/day according to a dose titration schedule. The primary endpoint was clinical response rate. Clinical response was defined as either complete response (CR), partial response (PR) (according to RECIST 1.1) or stable disease (SD) with improvement of erythema, edema and thickness. Exploratory objectives included histologic response, PET response and assessment of potential biomarkers for response in tumor tissue by IHC (e.g., ADBR 1/2, PD-L1).
Results
To date, 13 patients with a median age of 67 years (range 52-86) are enrolled and have initiated treatment. The median duration of treatment was 28 days (range 21-42 days). The median dose was 160 mg/day. Three patients showed exceptional good tolerance (blood pressure/heart rate) and could be escalated to the highest dose (240 mg/day). Two patients showed clinical response. The most common adverse event was grade 1/2 bradycardia (85%). There were no grade ≥3 adverse events. Preliminary IHC results showed ADBR2 overexpression in the majority of the tumors (12 out of 17 tumor samples, both in responders and non-responders). None of the tumors showed ADBR1 overexpression.
Conclusions
This window-of-opportunity trial did not demonstrate clinical efficacy of propranolol monotherapy in patients with angiosarcoma. Two out of 13 patients did however show clinical benefit. ADBR1 or 2 expression did not correlate with response. Translational research to better comprehend the anti-tumor activity of propranolol for adequate selection of patients in future studies is ongoing (e.g., immune system-based biomarkers).
Clinical trial identification
NCT04518124.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Anticancer Fund.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1840P - RNASEH2B loss and PARP inhibition (parpi) in metastatic castration resistant prostate cancer (mCRPC)
Presenter: Juliet Carmichael
Session: Poster session 15
1841TiP - Darolutamide plus androgen-deprivation therapy (ADT) in patients with high-risk biochemical recurrence (BCR) of prostate cancer: A phase III, randomized, double-blind, placebo-controlled study (ARASTEP)
Presenter: Alicia Morgans
Session: Poster session 15
1842TiP - Phase II randomized trial of two dose levels of vobramitamab duocarmazine in participants with metastatic castration resistant prostate cancer (mCRPC; TAMARACK)
Presenter: Johann de Bono
Session: Poster session 15
1922P - Immunosarc II master trial: phase II of sunitinib and nivolumab in vascular sarcomas cohort - A GEIS, ISG and UCL study
Presenter: Nadia Hindi Muñiz
Session: Poster session 15
1923P - Combined analysis of phase III ANNOUNCE study and phase II study exploring olaratumab in advanced soft tissue sarcoma
Presenter: Yoichi Naito
Session: Poster session 15
1924P - Targeting microenvironment and cellular immunity in sarcomas with trabectedin combined with metronomic cyclophosphamide: The TARMIC study
Presenter: Cheng-Ming Sun
Session: Poster session 15
1925P - Results of SOC-2082 phase II study using metronomic gemcitabine, doxorubicin, and docetaxel plus nivolumab as second/third-line therapy for advanced leiomyosarcoma
Presenter: Neal Chawla
Session: Poster session 15
1926P - Trabectedin plus radiotherapy on symptomatic advanced sarcoma patients: Results from the SYNERGIAS study - A Spanish group for research in sarcoma (GEIS) phase II study
Presenter: Javier Martin-Broto
Session: Poster session 15
1927P - Epithelioid hemangio-endothelioma (EHE) in NETSARC: The nationwide series of 267 patients over 12 years
Presenter: Axel Le Cesne
Session: Poster session 15
1928P - Differential presentation and outcome of sclerosing epithelioid fibrosarcoma (SEF) vs low grade fibromyxoid sarcoma (LGFMS): The nationwide series of 330 patients in NETSARC since 2010
Presenter: Jean-Yves Blay
Session: Poster session 15