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
1939P - phase I clinical results of SQ3370, a doxorubicin-based click chemistry therapeutic in advanced solid tumor patients
Presenter: Sant Chawla
Session: Poster session 15
1940P - Deep molecular profiling of advanced synovial sarcoma as a basis for interventional clinical trials
Presenter: Richard Schlenk
Session: Poster session 15
1941P - Preliminary efficacy and safety of SHR-2554 in advanced epithelioid sarcoma: A phase II trial
Presenter: Haiyan Hu
Session: Poster session 15
1942P - Non-metastatic malignant phyllodes tumors of the breast (B-MPT): A retrospective analysis from a referral center
Presenter: Carmine Valenza
Session: Poster session 15
1944P - MAGE-A4 and NY-ESO-1 expression analysed in a synovial sarcoma tissue micro-array
Presenter: Lore De Cock
Session: Poster session 15
1945P - Diagnostic and therapeutic impact of liquid biopsy in soft tissue sarcomas: A case series
Presenter: Tarek Assi
Session: Poster session 15
1946P - Bladder primary sarcomas (BSar): A genomic landscape and clinical outcomes study
Presenter: ALINA BASNET
Session: Poster session 15
1947P - Predictors and outcomes of recurrent retroperitoneal liposarcoma: New insights into its recurrence patterns
Presenter: Huan Deng
Session: Poster session 15
1948P - Concordance of the pathological diagnosis between local institutional and central judgment in high-grade non-round-cell sarcomas: A supplementary analysis of JCOG1306
Presenter: Eisuke Kobayashi
Session: Poster session 15