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. 2022 Dec 8:12:1042479.
doi: 10.3389/fonc.2022.1042479. eCollection 2022.

Transcription regulators and ultra-rare and other rare translocation-related sarcomas treated with trabectedin: A proof of principle from a post-hoc analysis

Emanuela Palmerini  1 , Roberta Sanfilippo  2 , Giovanni Grignani  3 , Angela Buonadonna  4 , Antonella Romanini  5 , Giuseppe Badalamenti  6 , Virginia Ferraresi  7 , Bruno Vincenzi  8 , Alessandro Comandone  9 , Antonio Pizzolorusso  10 , Antonella Brunello  11 , Fabio Gelsomino  12 , Tommaso De Pas  13 , Toni Ibrahim  1 , Lorena Gurrieri  14 , Federica Grosso  15 , Francesca Zanelli  16 , Maria Abbondanza Pantaleo  17 , Laura Milesi  18 , Libero Ciuffreda  19 , Vittorio Ferrari  20 , Emanuela Marchesi  21 , Irene Quattrini  1 , Alberto Righi  22 , Elisabetta Setola  23 , Elisa Carretta  1 , Paolo G Casali  2   24 , Piero Picci  21 , Stefano Ferrari  1
Affiliations

Transcription regulators and ultra-rare and other rare translocation-related sarcomas treated with trabectedin: A proof of principle from a post-hoc analysis

Emanuela Palmerini et al. Front Oncol. .

Abstract

Background: Among sarcomas, which are rare cancers with an incidence of <6 per 100.000/year cases, ultra-rare sarcomas have an incidence of approximately ≤1/1,000,000/year cases and altogether account for ~20% of all soft tissue sarcomas (STS) and bone sarcomas. The Italian Sarcoma Group has recently performed a non-interventional, retrospective TrObs study with data from 512 anthracycline-pretreated patients with advanced multiple STS histologies and treated with trabectedin (Palmerini, Cancers 2021; ClinicalTrials.gov Identifier: NCT02793050).

Methods: A post-hoc analysis of case series to evaluate the efficacy and safety of trabectedin on patients with ultra-rare and other rare translocation-related sarcomas included in TrObs study was performed. Main outcomes comprised investigator-assessed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety.

Results: Thirty-six patients (18 women) with ultra-rare and other rare sarcoma and a median age of 53.0 years (range: 22-81) were included. Most patients had solitary fibrous tumor (SFT; n=11) followed by epithelioid sarcoma (n=5), malignant peripheral nerve sheath tumor (MPNST; n=4), extraskeletal myxoid chondrosarcoma (EMC; n=3), desmoplastic small round cell tumor (DSRCT; n=3), and alveolar soft part sarcoma (ASPS), rhabdomyosarcoma and clear cell sarcoma (n=2 each). Thirty-five patients had metastatic disease and 23 patients received trabectedin as a second-line treatment. Among 35 patients evaluable for response, two patients with SFT and ASPS had a partial response and one patient with DSRCT obtained a complete response, reaching an ORR of 8.6% (95% CI: 2.8-23.4%). Among patients with an ORR, 6-months PFS was 100% in patients with ASPS, 45.7% in patients with SFT and 33.3% in those with DSRCT. Two patients with epithelioid sarcoma and myoepithelioma had disease stabilization lasting >24 months. Nine patients had at least one grade 3/4 adverse event, mostly being bone marrow toxicity (n=6).

Conclusions: Trabectedin has some anti-tumor activity in some ultra-rare and other rare sarcomas, particularly translocation-related sarcomas, with the well-known manageable safety profile.

Keywords: rare; sarcoma; soft tissue; translocation-related; ultra-rare.

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Conflict of interest statement

EP has served on an advisory board for Takeda, Amgen, Daiichi Sankyo, Lilly, Eusa Pharma, Deciphera, and SynOx Therapeutics and has received research support from Bristol Myers Squibb, Pfizer, PharmaMar, and Daiichi Sankyo. ABr is a consultant for Eli Lilly, Eisai, Glaxo-Smith Kline, Pharmamar and has received travel grants from PharmaMar, Takeda, and Ipsen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Kaplan-Meier plots of progression-free survival.
See this image and copyright information in PMC

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