A Phase II Multi-Center Trial of Trabectedin in Combination with Olaparib in Patients with Advanced Unresectable or Metastatic Sarcoma
Mené sur 29 patients atteints d'un sarcome de stade métastatique ou de stade avancé et non résécable, cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement combinant trabectédine et olaparib
Purpose: Soft tissue sarcoma (STS) are rare malignancies with poor prognosis and limited systemic treatment options. We conducted a phase II study to assess the efficacy and safety of trabectedin and olaparib in patients with advanced disease.
Patients and Methods: Patients with STS who received ≥ 1 prior therapy were recruited into two cohorts. Cohort 1 included leiomyosarcoma and liposarcoma; Cohort 2 included other histologies. All patients received trabectedin (1.1 mg/m2 24-hour infusion every 21 days) and olaparib (150 mg BID continuously). The study was conducted using a Simon Minimax two-stage design with a primary endpoint of objective response rate per RECIST 1.1.
Results: Twenty-nine patients enrolled (Cohort 1:16, Cohort 2:13); one patient in Cohort 2 was not evaluable. There were no confirmed objective responses in Cohort 1; best response was stable disease in 12 patients (75%) and progressive disease in 4 (25%). Two partial responses were observed in Cohort 2 (n=12). The most common adverse events were fatigue (75%), neutropenia (75%), anemia (68%), and thrombocytopenia (68%). Median progression free survival and overall survival for all patients was 3.5 (95% CI 3.3-8.2) and 13.2 months (95% CI 10.3-20.9), respectively. Next generation sequencing of 17 tumors revealed multiple abnormalities, most commonly in TP53, RB1, and ATRX.
Conclusions: Trabectedin plus olaparib conferred high rates of toxicity and failed to demonstrate objective responses in leiomyosarcoma and liposarcoma. Preliminary evidence of clinical benefit in two patients in cohort 2 suggests potential value of either or both drugs in other sarcomas.
Clinical Cancer Research , résumé, 2025