Anlotinib plus Epirubicin Followed by Anlotinib Maintenance as First-line Treatment for Advanced Soft-tissue Sarcoma: An Open-label, Single-arm, Phase II Trial

Abstract

Purpose: The treatment outcome for locally advanced or metastatic soft tissue sarcoma (STS) remains unsatisfactory. Anlotinib had demonstrated impressive activity in the subsequent-line treatment of STS. This study investigated the combination of anlotinib and epirubicin followed by anlotinib maintenance as first-line treatment for patients with advanced STS. Patients and methods: This prospective, open-label, single-arm, phase 2 trial was conducted in Zhongshan Hospital, Fudan university. Eligible patients were aged 18 years or older and had previously untreated, pathologically confirmed, unresectable locally advanced or metastatic STS. All patients received up to 6 cycles of anlotinib plus epirubicin followed by anlotinib maintenance until disease progression, unacceptable toxicity or death. The primary endpoint was the progression-free survival (PFS) rate at 6 months. The study was registered on chictr.org (identifier ChiCTR1900024928). Results: From June 2019 to August 2020, 30 patients were enrolled. By December 2021, the median PFS was 11.5 months (95% CI: 8.6-14.4 months), while the median overall survival (OS) was not reached (95% CI: NE-NE). The objective response rate (ORR) was 13.33% and the disease control rate (DCR) was 80.0%. The most common adverse events (AEs) included anemia (43.3%), nausea/vomiting (40.0%), fatigue (36.7%), leukopenia (30.0%) and proteinuria (10.0%), which were mainly of grade 1 or 2. The most frequent grade 3 or 4 AEs were anemia (10.0%), febrile neutropenia (33.3%), hypothyroidism (3.3%), and leukopenia (3.3%). No treatment-related death occurred. Conclusions: The combination of anlotinib and epirubicin followed by anlotinib maintenance demonstrated promising efficacy with a favorable safety profile.

Anlotinib as a maintenance treatment for advanced soft tissue sarcoma after first-line chemotherapy (ALTER-S006): a multicentre, open-label, single-arm, phase 2 trial

“… 38 , 39 These results were further confirmed by a recently reported prospective phase 2 clinical study. 40 However, the evidence supporting anlotinib as a switch maintenance treatment in patients with advanced STS who have achieved disease control with first-line chemotherapy is not sufficient. Only one single-centre, retrospective, small-sample (n = 21) study reported the efficacy of anlotinib maintenance treatment for patients with unresectable or metastatic STS who benefited from chemotherapy.…”

Case Report: Immunotherapy for low-grade myofibroblastic sarcoma of the pharynx

“…Another phase IIB trial conducted in the Chinese population also confirmed the positive efficacy of anlotinib in patients with advanced STS in a real-world setting ( 24 ). Furthermore, a recent clinical trial demonstrated that the combination of anlotinib and epirubicin followed by anlotinib treatment maintenance could serve as the first-line treatment for patients with advanced STS ( 25 ). On the other hand, immunotherapy was another possible strategy in the second-line treatment against advanced or metastatic STS.…”

A case report and literature review of a rare primary multiple small intestinal sarcomatoid carcinoma with co-driver gene mutations

“…However, for cases of SCA such as this one, in which PD-L1 expression is negative, targeted therapy with PD-L1 monoclonal antibodies may not yield signi cant bene ts (Jiang et al 2019). Numerous studies have reported that anlotinib has good anticancer activity against various solid tumours, such as soft tissue sarcoma (Wang et al 2022), non-small cell lung cancer (Han et al 2018), and small cell lung cancer (Zheng et al 2022), prolonging progression-free survival (PFS) and overall survival (OS). It is a novel multi-targeted tyrosine kinase inhibitor that can block angiogenesis induced by vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and broblast growth factor (FGF), effectively inhibiting tumour angiogenesis and inducing tumour apoptosis due to nutrient deprivation (Li 2021).…”