Outcome of patients (PTS) with advanced epithelioid hemangioendothelioma (EHE) after failure on sirolimus (S).
Authors: Giani Claudia , Miceli Rosalba , Baldi Giacomo Giulio , Brunello Antonella , Vincenzi Bruno , Morosi Carlo , Greco Francesca Gabriella , Gronchi Alessandro , Ingrosso Matilde , Frezza Anna Maria , Casali Paolo Giovanni , Ljevar Silva , Stacchiotti Silvia 
Published: June 2023

11574

Background: EHE is an ultra-rare sarcoma, showing a highly variable clinical behavior, from indolent to very aggressive. Systemic agents available for treatment of sarcoma have marginal activity in EHE. S showed antitumor effect in PDX models and pts affected by advanced EHE. However, clinical data on S in EHE are only retrospective and uncontrolled. This makes it difficult to interpret if the median progression-free survival (m-PFS) of 13 mos and the m-overall survival (m-OS) of 18.8 mos observed in the 38 progressive pts included in the largest series available (Stacchiotti et al, doi:10.1002/cncr.33247) were attributable to the antitumor effect of S or to EHE natural history. To fill this gap, we reviewed the outcome of pts included in this series who went off S. Methods: Clinical data of all EHE pts included in the above-mentioned retrospective study and treated with S for advanced disease between 2010 and 2019 were reviewed, focusing on pts who discontinued S for any reason. Progression was retrospectively categorized by RECIST 1.1 progressive disease (PD) and as “clinical progression” (CP), CP being defined as worsening of systemic symptoms and/or serosal effusion without criteria for RECIST PD. Survival analyses were performed by Kaplan-Meier method. OS was defined as the time from S start until death or last follow-up (FU), post-discontinuation OS (pOS) as the time from S discontinuation until death or last FU, post-discontinuation PFS (pPFS) as the time from S discontinuation until first evidence of progression (PD or CP) or death, post-re-challenge PFS (pR-PFS) as the time from S re-challenge until first evidence of progression (PD or CP) or death. Results: Of the 38 pts, 24 stopped S and were included in this analysis (median age = 47 yrs; serosal effusion yes/no = 9/15; S discontinuation due to: RECIST PD = 12, CP = 3, toxicity = 7; other = 2). After S discontinuation all pts had an event (PD or CP or death), and 13/24 (54%) pts did not receive further treatments, while 11/24 (46%) started again a systemic treatment. In particular, 6/24 (25%) restarted S (all after interval progression, PD or CP) with a new stable disease in 5/6 cases. At last FU, 6/24 (25%) pts were alive, 18/24 (75%) dead. At 62.2-mo m-FU (IQR 46-124), m-OS was 14.3 mos (95% CI, 7.3-21.2). Overall m-pPFS was 3.02 mos (95% CI, 1.6-4.4), m-pOS was 7.15 mos (95% CI, 4.4-9.9). m-pPFS of pts who discontinued S without evidence of progression (PD or CP) was also 3.02 mos (95% CI, 2.9-3.1). m-PFS following the re-challenge of S (m-pR-PFS) was unreached; 1 pt died following PD after 19 mos, 1 pt was alive and showed CP at 40 mos, 4 were alive and progression-free after 27, 31, 55, 94 mos. Conclusions: In our study the outcome of EHE pts who discontinued S was poor, with a m-pPFS of 3 mos and a m-pOS of 7 mos. However, pts who discontinued S for reasons other than progression benefited from S re-challenge, suggesting that in advanced EHE there is a subset of long-responders to S.