1652P - A prospective, single-arm phase II study of pegylated-liposome doxorubincin combined with ifosfamide as first-line treatment for patients with advanced or metastatic soft tissue sarcoma

Background

This prospective, single-arm phase II clinical trial was aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) combined with ifosfamide (IFO) for the first-line treatment of patients with advanced or metastatic soft tissue sarcoma (STS).

Methods

The enrolled patients received treatment of PLD 30 mg/m², d1, plus IFO 1.8 g/m², d1-5, repeatedly every 21 days. Treatment was continued until disease progression, unacceptable toxicities, patient death or up to 6 cycles. The primary endpoint was progression free survival (PFS). The second endpoints included overall response rate (ORR), overall survival (OS) and toxicities.

Results

A total of 69 patients with chemotherapy-naive advanced or metastatic STS were enrolled into this study between May 2015 and November 2019. Among them, 12 patients were synovial sarcoma，11 patients were leiomyosarcoma，9 patients were undifferentiated pleomorphic sarcoma , 8 patients were liposarcoma, 29 patients were other subtypes. All patients received 1-6 cycles of treatment, at a median of 6 cycles. The median follow-up time was 26.4 months (95% CI, 14.3 to 38.5 months). The median PFS was 7.4 months (95% CI, 5.1 to 9.7 months). The median OS was 24 months (95% CI, 11.4 to 36.6 months). In 69 patients, complete response was observed in 1 patient (1.4%), partial response (PR) was observed in 17 patients (24.6%), stable disease (SD) was observed in 38 patients (55.1%), progressive disease (PD) in 10 patients (14.5%) and not available in 3 patients (4.3%). The ORR was 26.1%. The disease control rate (DCR, CR+PR+SD) was 81.2%. In 12 patients with synovial sarcoma, 6 patients achieved PR, 6 patients were SD. The ORR was 50%. The DCR was 100%. The major grade 3-4 toxicities included leucopenia (56.5%), neutropenia (62.3%), anemia (17.4%), thrombopenia (7.2%), febrile neutropenia (7.2%), and vomiting (2.9%). No grade 3-4 cardiac toxicities were observed.

Conclusions

Combination therapy comprising PLD and IFO was active and well tolerated as first-line treatment for patients with advanced or metastatic STS, which warrants further research.

Clinical trial identification

NCT03268772.

Editorial acknowledgement

Legal entity responsible for the study

Fudan University Shanghai Cancer Center.

Funding

China Shijiazhuang Pharmaceutical Group Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.