First-Line Anlotinib Plus Chemo Approved in China for Advanced Soft Tissue Sarcoma

The indication for anlotinib hydrochloride capsules in China has been expanded to include the first-line treatment of patients with unresectable locally advanced or metastatic soft tissue sarcoma in combination with chemotherapy.1

Notably, this is the world’s first approval of anlotinib plus chemotherapy for this indication.

This approval was based on findings from a phase 3 study (NCT05121350), in which the combination of anlotinib and epirubicin improved the median progression-free survival (PFS) by 5.6 months in patients who received the anlotinib-based combination vs those who received epirubicin alone. At a median follow-up of 7.16 months, data presented at the 2025 ASCO Annual Meeting showed that the median PFS per blinded independent review committee (BIRC) was 8.57 months (95% CI, 7.79-10.12) among patients who received anlotinib in the intention-to-treat population (n = 135) compared with 3.02 months (95% CI, 2.33-4.30) among those who received epirubicin alone (n = 137; HR, 0.30; 95% CI, 0.21-0.44; stratified log-rank P < .001).2 The median investigator-assessed PFS was 8.57 months (95% CI, 7.79-10.51) vs 3.45 months (95% CI, 2.69-4.50), respectively (HR, 0.38; 95% CI, 0.27-0.53; stratified log-rank P < .001).

Additionally, the overall response rate (ORR) per BIRC was 17.8% (95% CI, 11.7%-25.3%) in the anlotinib arm vs 2.9% (95% CI, 0.8%-7.3%) in the epirubicin alone arm (P < .001).1,2 The disease control rate (DCR) with anlotinib was 79.3% (95% CI, 71.4%-85.8%); this rate was 54.7% (95% CI, 46.0%-63.3%) in the control arm (P < .001). Overall survival (OS) data were immature at the time of the presentation; however, investigators reported a trend toward a reduction in the risk of death in favor of the anlotinib arm (HR, 0.78; 95% CI, 0.49-1.25; stratified log-rank P = .3036).2

Diving Into the Phase 3 Trial Design

The phase 3 trial enrolled patients between 18 and 75 years of age with pathologically confirmed, unresectable, locally advanced or metastatic soft tissue sarcoma who had not received prior systemic anticancer therapy or who had disease progression at least 6 months after neoadjuvant or adjuvant therapy. Patients needed to have an ECOG performance status of 0 or 1. Sarcoma subtypes enrolled included leiomyosarcoma, synovial sarcoma, and undifferentiated sarcoma. Patients were excluded if they had Ewing sarcoma, non-pleomorphic rhabdomyosarcoma, alveolar soft tissue sarcoma, or clear cell sarcoma.

Patients were randomly assigned 1:1. During the combination phase, which lasted up to 6 cycles, patients received anlotinib at 12 mg daily for 2 weeks on and 1 week off plus epirubicin at 90 mg/m2 every 3 weeks; or placebo at 0 mg daily for 2 weeks on and 1 week off plus epirubicin at 90 mg/m2 every 3 weeks. At the end of the combination phase, patients without disease progression were treated during the maintenance phase with anlotinib at 12 mg daily or placebo at 0 mg daily for 2 weeks on and 1 week off.

PFS per BIRC per RECIST 1.1 criteria served as the primary end point. Secondary end points included OS, ORR, DCR, and safety.

Zooming in on Safety Data and Further Context

Any-grade treatment-emergent adverse effects (TEAEs) were observed in 97.0% of patients in the anlotinib arm vs 99.3% of those in the control arm. The most frequently reported any-grade TEAEs among patients who received anlotinib were neutropenia (71.1%), leukopenia (70.3%), and hypertriglyceridemia (47.4%).

Previously, the CSCO guidelines recommended anlotinib monotherapy in the second-line setting for the treatment of patients with soft tissue sarcoma.1 

References

1. Novotech supports groundbreaking approval of anlotinib combination therapy for advanced soft tissue sarcoma. News release. Novotech. August 29, 2025. Accessed August 29, 2025. https://novotech-cro.com/news/novotech-supports-groundbreaking-approval-anlotinib-combination-therapy-advanced-soft-tissue
2. Zhou Y, Niu X, Jiang T, et al. Anlotinib in combination with epirubicin followed by maintenance anlotinib versus placebo plus epirubicin as first-line treatment for advanced soft tissue sarcoma (STS): a randomized, double-blind, parallel-controlled, phase III study. J Clin Oncol. 2025;43(suppl 16):11501. doi:10.1200/JCO.2025.43.16_suppl.11501