(P 175) TRABECTEDIN PLUS RADIOTHERAPY ON SYMPHTOMATIC ADVANCED SARCOMA PATIENTS, RESULTS FROM THE SYNERGIAS STUDY: A SPANISH GROUP FOR RESEARCH IN SARCOMA (GEIS) PHASE II STUDY

Objective: Pain relief and improvement of quality of life (QoL) is a critical objective in the therapy of patients 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% according to RECIST by central radiological review. This study further explores this combination, with the aim of analyzing the QoL improvement in sarcoma patients.

Methods: Pattients with pretreated advanced/unresectable STS and symptomatic lesions were eligible to receive Trabectedin 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, and then continue with Trabectedin 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 patients were necessary.

Results: From June/2021 to March/2023, 33 patients were included (18 Male/15 Female, median age 53 years (22-75), median previous lines 1 (0-4), ECOG 0/1 in 15/18 patients) and 26 patients were evaluable for response (efficacy population). Among the 26 evaluable patients, ORR in the irradiated lesions according to RECIST and local assessment was 42.3% (1 Complete Response, 10 Partial Responses, 13 Stable Disease, 2 Progressive Disease). With a median FU of 7 months (95% CI 1-13), 18 patients have progressed, with a median PFS of 5.2 months (95% CI 3.77-6.62) and 6m-PFS 44% ( 95% CI 23-64). During therapy, 17/33 (55%) of patients 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%) patients and 16/33 (52%) of patients 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.

Conclusion: 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.