(P 016) ACTIVITY OF CHEMOTHERAPY IN MESENCHYMAL CHONDROSARCOMA: A MULTICENTRE RETROSPECTIVE ANALYSIS WITHIN THE ITALIAN SARCOMA GROUP

Objective: Data on the activity of systemic agents in mesenchymal chondrosarcoma (MCS), only retrospective and limited to case reports or small and heterogeneous series, report a median progression-free survival (m-PFS) to anthracycline-based regimens of approximately 6 months, while a longer disease control (m-PFS 12 months) was seen in the 3 pts from different series treated with trabectedin. This is to report the results of an Italian, multicentric, retrospective study on the activity of cytotoxic chemotherapy in patients affected by MCS, an ultra-rare sarcoma marked by the presence of HEY1-NCOA2 fusion, and characterised by a poor prognosis in the advanced phase.

Methods: Patients (pts) of any age with a centrally confirmed diagnosis of MCS treated in the Italian Sarcoma Group centres with anthracycline-based regimens and/or high-dose ifosfamide and/or trabectedin between 2000 and 2022 were retrospectively reviewed. Response was assessed retrospectively by a dedicated radiologist of each participating centre by RECIST v1.1. PFS and overall survival (OS) were estimated by Kaplan-Meier method. Duration of response (DoR) was calculated from the date of best response to the date of first evidence of progression for pts with complete response (CR) and partial response (PR).

Results: 36 pts were retrospectively identified (HEY1-NCOA2 positive = 23; ongoing = 13); median age = 30 (range = 8-70); M/F = 20 (56%) / 16 (44%); primary site = bone 23 (64%) / soft tissue = 13 (36%); pts with local disease treated with (neo)adjuvant chemotherapy followed by complete surgical resection = 21 (58%), pts with advanced disease = 15 (42%). Thirty-five (95%) pts received an anthracycline-based regimen (19 (54%) = Ewing-like, 14 (40%) = anthracycline + ifosfamide, 1 (3%) = anthracycline + cisplatin, 1 (3%) = anthracycline alone), 4 (11%) = high-dose ifosfamide, 4 (11%) = trabectedin. Thirteen (36%) pts received >1 treatment line.
In the anthracycline-based group, 32/35 (91%) pts were evaluable for response (2 adjuvant; 1 treated with concomitant radiotherapy). 18/32 (56%) were treated in neoadjuvant setting, 14/32 (44%) for advanced disease. Median number of cycles was 5 (range 1-13). Best response was: 1 (3%) CR, 9 (28%) PR, 16 (50%) SD, 6 (19%) PD, for an ORR = 31%. At a m-FU of 45 mos, 12/18 (66%) pts with local disease were disease-free, with a m-RFS of 88 mos (CI:46-NE), while m-OS was not reached (CI:NE-NE). At a m-FU of 12 months, 4/14 pts with advance disease were progression-free, with a m-PFS of 5.7 mos (CI:4.5-13.0) and a m-DoR of 10.2 mos (range: 5.6-11.5), while m-OS was 25 mos (CI:19-NE).
In the high-dose ifosfamide group, 4 pts were evaluable for response; 1/4 (25%) pt was treated for localized disease and 3/4 (75%) pts for advanced disease. Median number of cycles was 2 (range 1-3). Best response was: 1 SD (25%), 3 PD (75%). For pts with advanced disease, at a m-FU of 3.5 mos, m-PFS was 2.8 mos (CI:1.4-NE) and m-OS was 4.8 mos (CI:NE-NE).
In the trabectedin group, 4 pts were evaluable for response, all treated for advanced disease. Median number of cycles was 20 (range 8-25). Best response was: 4 SD (100%). At a m-FU of 36.8 mos, m-PFS was 16.7 mos (CI: 9.6-NE), with 3 pts remaining on therapy for >1 year. m-OS was 34.3 mos (CI 11.4-NE).

Conclusion: As reported in the literature, our retrospective study confirmed that anthracycline-based regimens are active in MCS, but the duration of the benefit is limited. Trabectedin, although with no dimensional responses, achieved a prolonged disease control, lasting >1 year in three out of four pts. A phase II single arm trial with trabectedin in MCS is ongoing within the Italian Sarcoma Group.