1926P - Trabectedin plus radiotherapy on symptomatic advanced sarcoma patients: Results from the SYNERGIAS study - A Spanish group for research in sarcoma (GEIS) phase II study

Background

Pain relief and improvement of quality of life (QoL) is a critical objective in the therapy of patients (pts) with symptomatic advanced soft-tissue sarcoma (STS). The combination of trabectedin (T) and low-dose radiotherapy (RT) showed unprecedent activity in a previous study showing an overall response rate (ORR) of 60% by central review. This study further explores this combination, with the aim of analyzing the QoL improvement in sarcoma patients.

Methods

Pts with pretreated advanced/unresectable STS and symptomatic lesions were eligible to receive T 1,5mg/m² every 24h and RT 30Gy in 10 fractions (or 45 Gy in 25 fractions if the lesion was in limbs) on the symptomatic lesion/s, then T up to progression or unacceptable toxicity. Primary end-point was ORR by RECIST on the irradiated lesion. Secondary endpoints included QoL assessments (Brief pain inventory (BPI), EORTC QLQ C30), progression-free survival (PFS) and overall survival (OS). With H0 (10%), H1 (35%), (α 0.05 and β error 0.1), 27 evaluable pts were necessary.

Results

From June/2021 to March/2023, 33 pts were included (18M/15F, median age 53y (22-75), median previous lines 1 (0-4), ECOG 0/1 in 15/18 pts) and 26 pts were evaluable for response (efficacy population). Among the 26 evaluable pts, ORR in the irradiated lesions according to local assessment was 42.3% (1 CR, 10 PR, 13 SD, 2 PD). With a median FU of 7 months (mos) (95% CI 1-13), 18 pts have progressed, with a median PFS of 5.2 mos (95% CI 3.77-6.62) and 6m-PFS 44% (95% CI 23-64). During therapy, 17/33 (55%) of pts experienced a decrease of at least 2 points in the worst pain assessment of the BPI, with a median reduction of 2 points (range 0-8). 20/33 (64%) pts and 16/33 (52%) of pts reported an improvement of at least 1 point (on a scale 1-7) in their global health assessment and in their own QoL evaluation respectively. The main treatment-related G3-4 toxicities were neutropenia (18.2%), febrile neutropenia (9.1%), and ALT increased (9.1%). No toxic deaths have occurred.

Conclusions

Trabectedin plus palliative RT is a safe and active therapeutic regimen, able to induce clinical improvement in more than half of symptomatic sarcoma patients, and with a manageable toxicity profile.

Clinical trial identification

NCT05131386.

Editorial acknowledgement

Legal entity responsible for the study

Grupo Español de Investigación en Sarcomas (GEIS).

Funding

PharmaMar.

Disclosure

J. Martin-Broto: Financial Interests, Personal, Advisory Board, Honoraria: Lilly, PharmaMar, Eisai, Bayer, Roche, Boehringer Ingelheim, Amgen; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Advisory Board, Speaker: Tecnofarma, Asofarma; Financial Interests, Institutional, Coordinating PI: PharmaMar, Eisai, Novartis, IMMIX Biopharma, Lixte, Karyopharm, Bayer, Celgene, Pfizer, BMS, Lilly; Financial Interests, Institutional, Local PI: Blueprint, Deciphera, Nektar, Forma, Amgen, Daiichi Sankyo, Arog, Adaptimmune, GSK, Ran Therapeutics, Inhibrx, Ayala Pharmaceuticals, Philogen, Cebiotex, PTC Therapeutics, Inc. and SpringWorks therapeutics. J. Cruz Jurado: Financial Interests, Personal, Advisory Board: PharmaMar, Roche, Lilly, Pfyzer, Novartis, Gilead, AstraZeneca, Daiichi Sankyo, Seagen, GSK, Bayer; Financial Interests, Personal, Invited Speaker: PharmaMar, Roche, Lilly, Pfizer, Novartis, Eisai, Gilead, AstraZeneca, Daiichi Sankyo, Seagen, Esteve; Financial Interests, Personal, Steering Committee Member: Roche. R.M. Alvarez: Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Roche; Financial Interests, Personal, Other, conference registration: MSD Oncology; Financial Interests, Institutional, Coordinating PI: Roche; Financial Interests, Personal and Institutional, Coordinating PI: Janssen Oncology, Rain Therapeutics, Boehringer Ingelheim, Cebiotex, Novartis. C.M. Valverde Morales: Financial Interests, Personal, Advisory Board: PharmaMar, Bayer, GSK, Mundipharma, Lilly, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Local PI, Clinical Trial: Adaptimmune, Karyopharm, Lilly, Foghorn Therapeutics, Ayala therapeutics, Inhibrx; Financial Interests, Institutional, Coordinating PI, Clinical Proyect: Bayer; Non-Financial Interests, Member of Board of Directors, President 2018-ongoing: GEIS- Spanish Sarcoma Group for Research. A. Redondo Sanchez: Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Institutional, Advisory Board: PharmaMar. D. Da Silva Moura: Financial Interests, Institutional, Research Funding: PharmaMar; Financial Interests, Personal, Invited Speaker: Tecnofarma. N. Hindi Muñiz: Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Invited Speaker: PharmaMar, Tecnofarma; Financial Interests, Institutional, Research Funding: PharmaMar, Lixte, ImmixBio, Boehringer Ingelheim, Ayala, Deciphera, Inbrx, Phillogen, Lilly; Financial Interests, Personal, Advisory Role: GSK. All other authors have declared no conflicts of interest.