TY - JOUR
T1 - Activity of sirolimus in patients with progressive epithelioid hemangioendothelioma: A case-series analysis within the Italian Rare Cancer Network
AU - Stacchiotti, Silvia
AU - Simeone, Noemi
AU - Lo Vullo, Salvatore
AU - Baldi, Giacomo G.
AU - Brunello, Antonella
AU - Vincenzi, Bruno
AU - Palassini, Elena
AU - Dagrada, Gian Paolo
AU - Collini, Paola
AU - Morosi, Carlo
AU - Greco, Francesca G.
AU - Sbaraglia, Marta
AU - Dei Tos, Angelo P.
AU - Mariani, Luigi
AU - Frezza, Anna Maria
AU - Casali, Paolo G.
N1 - Funding Information:
Silvia Stacchiotti reports personal fees from Bayer, Bavarian Nordic, Deciphera, Daiichi, Eli Lilly, Epizyme, Karyopharm, MaxiVax, PharmaMar, and Takeda; honoraria from Eli Lilly and PharmaMar; travel grants from PharmaMar; and institutional research funding from Advenchen, Amgen Dompe, AROG, Bayer, Blueprint Medicines, Daiichi Sankyo Pharma, Deciphera, Eli Lilly, Epizyme, GSK, Karyopharm, Novartis, Pfizer, PharmaMar, and SpringWorks, all outside the submitted work. Giacomo G. Baldi reports honoraria from Eli Lilly, Eisai, and PharmaMar; travel grants from PharmaMar, Pfizer, and Eli Lilly; and personal fees from AboutEvents, EditaMed, and Eli Lilly, all outside the submitted work. Antonella Brunello reports personal fees from Eisai, Eli Lilly, and Roche and travel grants from PharmaMar and Ipsen, all outside the submitted work. Bruno Vincenzi reports personal fees from Eisai, Eli Lilly, Novartis, PharmaMar, and Abbott; paid testimony for Abbott; and institutional research funding from Eli Lilly, Novartis, and PharmaMar, all outside the submitted work. Elena Palassini reports institutional research funding from Advenchen, Amgen Dompe, AROG, Bayer, Blueprint Medicines, Daiichi Sankyo Pharma, Deciphera, Eli Lilly, Epizyme, GSK, Karyopharm, Novartis, Pfizer, PharmaMar, and SpringWorks, all outside the submitted work. Marta Sbaraglia reports travel grants from PharmaMar, outside the submitted work. Angelo P. Dei Tos reports personal fees from Bayer and Roche and travel grants from PharmaMar, outside the submitted work. Anna Maria Frezza reports institutional research funding from Advenchen, Amgen Dompe, AROG, Bayer, Blueprint Medicines, Daiichi Sankyo Pharma, Deciphera, Eli Lilly, Epizyme, GSK, Karyopharm, Novartis, Pfizer, PharmaMar, and SpringWorks, all outside the submitted work. Paolo G. Casali reports personal fees from Bayer, Glaxo, and Novartis and institutional research funding from Advenchen, Amgen Dompe, AROG, Bayer, Blueprint Medicines, Daiichi Sankyo Pharma, Deciphera, Eli Lilly, Epizyme, GSK, Karyopharm, Novartis, Pfizer, PharmaMar, and SpringWorks, all outside the submitted work. The remaining authors made no disclosures.
Publisher Copyright:
© 2020 American Cancer Society
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2/15
Y1 - 2021/2/15
N2 - Background: The objective of this study was to report on a retrospective series of patients with epithelioid hemangioendothelioma (EHE) who received treatment with sirolimus within the Italian Rare Cancer Network. Methods: From January 2005, 38 adult patients with advanced EHE received continuous-dosing sirolimus, 5 mg daily, until they developed either toxicity or disease progression. Disease progression in the 6 months before the start of treatment was required. Each pathologic diagnosis was reviewed. The daily dose of sirolimus was adjusted based on plasma levels. Response was retrospectively assessed by local investigators using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST). Survival was estimated using the Kaplan-Meier method. Results: All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven patients were evaluable for response (there was 1 early interruption). The best RECIST responses were a partial response in 4 patients (10.8%), stable disease in 28 patients (75.7%), and disease progression in 5 patients (13.5%). At a 41.5-month median follow-up (interquartile range [IQR], 23.9-56.8 months), the median PFS was 13 months (95% CI, 3.7 months to not estimated [NE]), and the median OS was 18.8 months (95% CI, 10.6 months to NE). In patients who had serosal effusions at baseline, the median PFS was 4.8 months (IQR, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 months), compared with 47.8 months (IQR, 11.4 months to NE) and 47.8 months (IQR, 15.7 months to NE), respectively, in patients without serosal effusions. Overall, sirolimus was fairly well tolerated, with 10 patients reporting irregular menstruation/ovary disfunction. Conclusions: The current results confirm that sirolimus is active in EHE, leading to prolonged stabilization in most patients who present without serosal effusions. Serosal effusions are confirmed as an unfavorable prognostic sign associated with short survival, and sirolimus displays limited activity in this subgroup.
AB - Background: The objective of this study was to report on a retrospective series of patients with epithelioid hemangioendothelioma (EHE) who received treatment with sirolimus within the Italian Rare Cancer Network. Methods: From January 2005, 38 adult patients with advanced EHE received continuous-dosing sirolimus, 5 mg daily, until they developed either toxicity or disease progression. Disease progression in the 6 months before the start of treatment was required. Each pathologic diagnosis was reviewed. The daily dose of sirolimus was adjusted based on plasma levels. Response was retrospectively assessed by local investigators using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST). Survival was estimated using the Kaplan-Meier method. Results: All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven patients were evaluable for response (there was 1 early interruption). The best RECIST responses were a partial response in 4 patients (10.8%), stable disease in 28 patients (75.7%), and disease progression in 5 patients (13.5%). At a 41.5-month median follow-up (interquartile range [IQR], 23.9-56.8 months), the median PFS was 13 months (95% CI, 3.7 months to not estimated [NE]), and the median OS was 18.8 months (95% CI, 10.6 months to NE). In patients who had serosal effusions at baseline, the median PFS was 4.8 months (IQR, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 months), compared with 47.8 months (IQR, 11.4 months to NE) and 47.8 months (IQR, 15.7 months to NE), respectively, in patients without serosal effusions. Overall, sirolimus was fairly well tolerated, with 10 patients reporting irregular menstruation/ovary disfunction. Conclusions: The current results confirm that sirolimus is active in EHE, leading to prolonged stabilization in most patients who present without serosal effusions. Serosal effusions are confirmed as an unfavorable prognostic sign associated with short survival, and sirolimus displays limited activity in this subgroup.
KW - chemotherapy
KW - epithelioid hemangioendothelioma
KW - metastasis
KW - prognosis
KW - sarcoma
KW - serosal effusion
KW - sirolimus
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U2 - 10.1002/cncr.33247
DO - 10.1002/cncr.33247
M3 - Article
C2 - 33107985
AN - SCOPUS:85093936675
VL - 127
SP - 569
EP - 576
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 4
ER -