Anlotinib Plus Epirubicin Receives World's First Approval in China for Advanced Soft Tissue Sarcoma
核心洞察
China has approved anlotinib hydrochloride capsules plus chemotherapy as first-line treatment for unresectable locally advanced or metastatic soft tissue sarcoma, marking the world's first approval of this combination for this indication.
The approval was based on phase 3 trial results showing the combination improved median progression-free survival by 5.6 months compared to epirubicin alone (8.6 vs 3.0 months, HR 0.30, P < .001).
The anlotinib-epirubicin combination demonstrated superior overall response rate (17.8% vs 2.9%) and disease control rate (79.3% vs 54.7%) with manageable toxicity profiles.
China has granted approval for anlotinib hydrochloride capsules in combination with chemotherapy as first-line treatment for patients with unresectable locally advanced or metastatic soft tissue sarcoma, representing the world's first approval of this combination for this indication.
The regulatory decision was based on compelling results from a multicenter, randomized, double-blind phase 3 study (NCT05121350) that demonstrated significant efficacy benefits of anlotinib plus epirubicin compared to epirubicin alone. At a median follow-up of 7.16 months, the combination improved median progression-free survival by 5.6 months.
Phase 3 Trial Results Drive Approval
The pivotal trial enrolled 272 patients aged 18 to 75 years with pathologically confirmed, unresectable locally advanced or metastatic soft tissue sarcoma who had not received prior systemic anticancer therapy or experienced disease progression at least 6 months following neoadjuvant or adjuvant therapy.
Patients were randomly assigned 1:1 to receive either anlotinib at 12 mg once daily via a 2-week-on and 1-week-off dosing schedule plus epirubicin at 90 mg/m² every 3 weeks, or placebo plus epirubicin at the same dose. Those without disease progression during the combination phase proceeded to maintenance therapy with anlotinib or placebo.
The median progression-free survival per blinded independent central review was 8.57 months (95% CI, 7.79-10.12) in the anlotinib combination arm (n=135) compared with 3.02 months (95% CI, 2.33-4.30) in the control arm (n=137), representing a 70% reduction in the risk of disease progression (HR, 0.30; 95% CI, 0.21-0.44; P < .001).
"An unprecedented median PFS was observed with [anlotinib plus epirubicin]," said Yuhong Zhou, MD, of Zhongshan Hospital at Fudan University in Shanghai, China, during the presentation at the 2025 ASCO Annual Meeting. "This phase 3 evidence support this anti-angiogenic TKI plus anthracycline [combination] as a new standard treatment for advanced soft tissue sarcoma."
Superior Response Rates and Disease Control
The combination therapy demonstrated markedly superior response rates compared to chemotherapy alone. The overall response rate per blinded independent review committee was 17.8% (95% CI, 11.7%-25.3%) in the anlotinib arm versus 2.9% (95% CI, 0.8%-7.3%) in the control arm (P < .001).
Disease control rates also favored the combination, reaching 79.3% (95% CI, 71.4%-85.8%) compared to 54.7% (95% CI, 46.0%-63.3%) with epirubicin alone (P < .001). Subgroup analysis revealed that the progression-free survival benefit favored the investigational arm in every patient subgroup except for those with target lesions in the lungs only.
Although overall survival data were immature at the time of presentation, investigators reported a trend toward reduced risk of death in favor of the anlotinib combination (HR, 0.78; 95% CI, 0.49-1.25).
Manageable Safety Profile
The safety analysis included patients with various soft tissue sarcoma subtypes, including leiomyosarcoma (28.1% vs 27.7%), synovial sarcoma (11.9% vs 13.1%), and other histologies. Any-grade treatment-emergent adverse effects occurred in 97.0% of patients in the anlotinib arm versus 99.3% in the control arm.
The most common any-grade treatment-emergent adverse effects in the anlotinib combination included neutropenia (71.1%), leukopenia (70.3%), and hypertriglyceridemia (47.4%). In the control arm, common adverse effects consisted of leukopenia (61.3%), neutropenia (55.5%), and anemia (49.6%).
Grade 3 or higher treatment-emergent adverse effects occurred in 69.6% of patients receiving the combination versus 59.1% in the control arm. Treatment-related deaths occurred at similar rates (3.7% vs 3.6%).
"The manageable toxicity confirmed the clinical feasibility of this combination therapy," Zhou noted.
Clinical Impact and Treatment Landscape
This approval represents a significant advancement in soft tissue sarcoma treatment. Previously, CSCO guidelines recommended anlotinib monotherapy only in the second-line setting for patients with soft tissue sarcoma. The new first-line indication expands treatment options for patients with this challenging malignancy.
The study excluded patients with certain sarcoma subtypes including Ewing sarcoma, non-pleomorphic rhabdomyosarcoma, alveolar soft tissue sarcoma, and clear cell sarcoma, indicating the approval applies to specific histological subtypes of soft tissue sarcoma.
At baseline, patients had a median age of 53.0 years in the combination arm and 58.0 years in the control arm. Most patients were male (60.0% vs 50.4%) and had an ECOG performance status of 1 (68.9% vs 66.4%), with the majority having metastatic sites beyond the lungs (93.3% vs 92.0%).