Conclusión : These findings confirm that T can be an appropriate option for both elderly pts and those unsuitable for A-CT.
TRABECTEDIN AS FIRST LINE IN ADVANCED SOFT TISSUE SARCOMA (STS) PATIENTS UNFIT TO RE-CEIVE STANDARD CHEMOTHERAPY: SAFETY AND EFFICACY FROM TR1US STUDY .
Federica Grosso ; Lorenzo D’Ambrosio ; Toni Ibrahim ; Stefano Tamberi ; Emanuela Palmerini ; Danila Comandini ; Giacomo Giulio Baldi ; Marina Bergaglio8 ; Andrea De Censi10; Massimo Zucchetti11; Emanuela Marchesi3 ; Matteo Puntoni12; Domenico Marra10; Maurizio D’Incalci11; Giovanni Grignani2
Objective: About 50% of STS patients (pts) develop me-tastases within 3 years from diagnosis and die for disease.
Trabectedin (T) has been registered for advanced STS pts who failed or are unsuitable for anthracycline-based chemotherapy (A-CT). Activity and toxicity of T is widely assessed in 2ndline, but few data are available for T as 1st line when medical conditions contraindicate A-CT.
This study aimed at assessing the activity, tolerability and pharmacokinetic (PK) of 1st line T in advanced STS pts unfit to receive A-CT.
Methods: Pts received intravenous T 1.3-1.5 mg/m2 as a 24-h infusion q3weeks until progression/unacceptable tox-icity. Principal inclusion criteria were: unsuitability to receive A-CT (i.e.: stable arrhythmia, previous myocardial infarction [MI]; PS≥2, age≥80 years), ECOG 0-2, GFR ≥30 mL/min, adequate organ function. Sample size was calculated using the Bryant & Day design. T plasma concentrations were measured by HPLC-MS/MS and PK parameters calculated by the software NCPKA v.2.4. Response, progression-free survival (PFS) and overall survival (OS) were assessed according to RECIST 1.1 and Kaplan Meier method, re- spectively.
Results: From 2/2014 to 12/2015, 24 pts (12 female), me- dian age 78 (range 64-89, IQR 74-82) entered the study.
Histotypes were: leiomyosarcoma 11 (46%), liposarcoma 8 (33%), other STS 5 (21%). Only 2 pts had previously received adjuvant A-CT. Overall 114 courses of T were delivered with a median of 4 cycles (range 1-16, IQR 3-6).
All pts received steroid premedication. The steady-state plasma concentration and the clearance of T were 1.55 ng/ mL and 39 ml/min/m2 . We observed 4 pts not evaluable for response (17%), 13 SD (54%), 2 PR (8%) and 5 PD (22%) for an overall disease control rate (DCR) of 62%.
At a median follow-up of 14 months (mos), median PFS was 4 (IQR 2-25), and median OS 9 (IQR 4-25) mos. Drug related G3-4 adverse events (AEs) were neutropenia (37,5%), fatigue (21%) and transaminitis (12.5%), with 2 serious AEs deemed possibly related to T: thoracic pain with reversible heart failure in a pt with history of MI, and creatinine increase in a pt with huge abdominal mass. No T-related death was observed.
Conclusion: In this unfit pts population the DCR was 62% and median PFS 4 mos superimposable to that of previous studies. PK values were in the range of those reported for younger adult population. These findings confirm that T can be an appropriate option for both elderly pts and those unsuitable for A-CT.