1950P - A single-arm, phase II clinical trial of neoadjuvant pegylated liposomal doxorubicin plus anlotinib in locally advanced soft tissue sarcoma

Background

Neoadjuvant therapy might improve excision and limb salvage rates in locally advanced soft tissue sarcomas (STS). This phase II trial aimed to investigate the safety and activity of neoadjuvant pegylated liposomal doxorubicin (PLD) plus anlotinib in local advanced STS.

Methods

In this prospective, single-center, single-arm phase II study, major eligible criteria were locally advanced, non-metastasis, treatment-naive STS, age at 14-75 years old, pathological stage IIb/III, ECOG PS 0-2. Patients received PLD (50mg/m², IV, D1, Q3W) and anlotinib (12mg/d, PO, D8-21, Q3W) for 2∼4 cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), pathological complete response (ypT0/is ypN0, pCR) and safety.

Results

From November 2020 to November 2022, 45 patients were recruited. The median age was 47 years (range, 15-75) and 19 were female. The predominant histologies included Spindle cell sarcoma 7 (15.56%), Myxofibrosarcoma 5 (11.11%), Myxoid liposarcoma 5 (11.11%), Malignant peripheral nerve sheath tumor 4 (8.89%), Synovial sarcoma 4 (8.89%), Leiomyosarcoma 3 (6.67%). Median treatment cycles of neoadjuvant therapy were 2 (range, 1-4). The ORR and DCR of 29 patients with at least one assessment as Choi criteria was 62.1% and 100%, respectively. Of 39 (86.67%) patients underwent radical resection, 33 (84.62%) patients had an R0 resection. With a median follow-up time of 11.47 months, the median OS were not reached. Median PFS was 14.19 months, and the 1-year OS rate was 84.23%. The limb salvage rates was observed in 39 (100%) patients. The most common adverse events (AEs) of all grade were mucositis oral 19 (42.22%), proteinuria 13 (28.89%), neutropenia 12 (26.67%), and leucopenia 11 (24.44%). Grade 3/4 AEs were 13 (28.89%). PLD plus Anlotinib was well tolerated without significant unexpected toxic effects.

Conclusions

PLD combined with Anlotinib showed a promising efficacy and acceptable toxicity for patients with locally advanced soft tissue sarcomas, suggesting a potential therapeutic option for this population.

Clinical trial identification

NCT04765228.

Editorial acknowledgement

Legal entity responsible for the study

Y. Chen and W. Sun.

Funding

CSPC Ouyi Pharmaceutical Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.