Activity of sirolimus in advanced epithelioid hemangioendothelioma (EHE): A retrospective analysis within the Italian Rare Tumor Network (RTR).

person Noemi Simeone Adult Mesenchymal and Rare Tumor Unit, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy info_outline Noemi Simeone, Giacomo Giulio Baldi, Anna Maria Frezza, Elena Palassini, Bruna Bianca Lopes David, Bruno Vincenzi, Antonella Brunello, Gianpaolo Dagrada, Paola Collini, Carlo Morosi, Angelo Paolo Dei Tos, Paolo Giovanni Casali, Silvia Stacchiotti

Authors person Noemi Simeone Adult Mesenchymal and Rare Tumor Unit, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy info_outline Noemi Simeone, Giacomo Giulio Baldi, Anna Maria Frezza, Elena Palassini, Bruna Bianca Lopes David, Bruno Vincenzi, Antonella Brunello, Gianpaolo Dagrada, Paola Collini, Carlo Morosi, Angelo Paolo Dei Tos, Paolo Giovanni Casali, Silvia Stacchiotti Organizations Adult Mesenchymal and Rare Tumor Unit, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Adult Mesenchymal and Rare Tumor Unit, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Milan, Italy, Medical Oncology Department, Campus Bio-Medico University of Rome, Rome, Italy, Department of Clinical and Experimental Oncology, Medical Oncology 1 Unit, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy, Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Soft Tissue and Bone Pathology, Histopathology and Pediatric Pathology Unit, Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Department of Pathology, General Hospital of Treviso, Treviso, Italy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Abstract Disclosures Research Funding Other Background: EHE is an exceedingly rare soft tissue sarcoma (STS) with no active standard treatment available in advanced patients (pts). We already reported on the activity of sirolimus in a retrospective series of 18 EHE treated within the RTR. We herein update this series on a longer follow-up in a larger number of pts. Methods: Adult pts affected by an advanced, progressive and centrally confirmed EHE treated with sirolimus within the RTR from 2006 to 2018 were retrospectively reviewed. Sirolimus was administered at the starting dose of 5 mg/day, until toxicity or progression. Sirolimus dose was adjusted according to plasma levels (target: 15–20 ng/dL). Response was assessed by RECIST 1.1. Survival was estimated by Kaplan-Meier method. Results: 33 patients were retrospectively identified (median age = 47 years, female = 20 (60%), male = 13 (40%); pretreated = 8, naïve = 25; presence of pleural effusion at baseline = 6). All patients had metastatic disease and evidence of disease progression before starting sirolimus. Mean sirolimus daily dose was 5 mg (range 2-10). 9 pts are still on therapy, 24 stopped sirolimus (13 progression, 5 toxicity, 6 other). 31 pts were evaluable for response (2 pts too early). Best RECIST response was: 1 (3.2%), PR, 26 (83.8%) SD, 4 (12.9%) progression. At a 14-mo median FU, median PFS (m-PFS) was 12.3 mos (range 8–15) and median OS (m-OS) was 19 mos (range 1–40). Pleural effusion correlated with a short m-PFS (3.4 vs 14.3 mos in patients without pleural effusion, p = 0.006) and m-OS (10.6 vs 40 mos in patients without pleural effusion, p <0.0001). Amongst those without pleural effusion, the proportion of pts being progression free at > 24 mos was 23%, with 54 % being alive. Conclusions: We selected pts with advanced EHE with clear evidence of disease progression. This singles out a subgroup of EHE pts with a bad prognosis. Prognosis was shown to be exceedingly bad when there was evidence of serosal effusion, and sirolimus was not effective. Though in an uncontrolled setting, apparently sirolimus is able to slightly prolong PFS and, above all, to allow mid-term freedom of progression in roughly 25% of pts.