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A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing Neoadjuvant Therapies
Published on: July 28, 2020
Rechallenge with Multi-Targeted Tyrosine Kinase Inhibitors in Patients with Advanced Soft Tissue Sarcoma: A
Jie Liu1, Yao-Tiao Deng1, Xin Wu1
1Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
Purpose:
Chemotherapy and multi-targeted tyrosine kinase inhibitors (TKI) are important treatments for advanced soft tissue sarcomas, but the following treatment remains unclear after the failure of these drugs. This retrospective study investigated the efficacy and safety of multi-targeted TKI rechallenge in patients with advanced soft tissue sarcoma after the failure of previous TKI treatment.
Patients And Methods:
Gastrointestinal stromal tumors, dermatofibrosarcoma protuberans and anaplastic lymphoma kinase translocation-positive inflammatory myofibroblastic tumor were excluded. Eligible patients included those diagnosed with advanced soft tissue sarcoma, progressed after the initial TKI treatment, and received the same or other TKI therapies. Treatment response, adverse events, median progression-free survival and overall survival were analyzed.
Results:
Twenty-six eligible patients were included. Nineteen patients had previously received chemotherapy, and all patients had received at least 1.5 months of initial TKI treatment. During the TKI rechallenge, patients were treated with anlotinib (n =16), lenvatinib (n =3), apatinib (n =2), pazopanib (n =2), axitinib (n =2) or regorafenib (n =1). No patients achieved responses. Nine (34.6%) patients had stable disease confirmed by a second imaging scan, and 5 (19.2%) patients had stable disease that was not confirmed by a second scan. The estimated median progression-free survival and overall survival were 3.3 months and 11.7 months, respectively. Grade 3/4 adverse events occurred in 6 (23.1%) patients and were manageable.
Conclusion:
Our findings suggest that multi-targeted TKI rechallenge may provide potential clinical benefits for patients with advanced soft tissue sarcoma after their previous TKI treatment.
Insights
Rechallenging patients with advanced soft tissue sarcoma with multi-targeted tyrosine kinase inhibitors (TKI) after initial TKI failure showed potential clinical benefits. Stable disease was observed in over half of patients, with manageable adverse events.
Area of Science:
- Oncology
- Medical Science
- Pharmacology
Background:
- Advanced soft tissue sarcomas (STS) pose treatment challenges, especially after failure of initial therapies like chemotherapy and multi-targeted tyrosine kinase inhibitors (TKI).
- Optimal subsequent treatment strategies for advanced STS following TKI failure remain an area of active investigation.
Purpose of the Study:
- To investigate the efficacy and safety of rechallenging patients with advanced STS with multi-targeted TKI after prior TKI treatment failure.
Main Methods:
- A retrospective study included patients with advanced STS who progressed after initial TKI therapy and received subsequent TKI rechallenge.
- Exclusion criteria included specific STS subtypes like GIST, DFSP, and ALK-translocation-positive tumors.
- Treatment response, adverse events, progression-free survival (PFS), and overall survival (OS) were analyzed.
Main Results:
- Twenty-six eligible patients received TKI rechallenge with various agents (anlotinib, lenvatinib, etc.).
- No complete or partial responses were observed; however, 34.6% achieved confirmed stable disease (SD) and an additional 19.2% had unconfirmed SD.
- Median PFS was 3.3 months and median OS was 11.7 months, with manageable Grade 3/4 adverse events in 23.1% of patients.
Conclusions:
- Multi-targeted TKI rechallenge may offer clinical benefits for advanced STS patients who have previously failed TKI therapy.
- The observed stable disease rates and survival metrics suggest TKI rechallenge as a potentially viable option in this patient population.
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