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Updated: Aug 15, 2025
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
The Outcome of Discontinuing Tyrosine Kinase Inhibitors in Advanced Sarcoma Following a Favorable Tumor Response to
Zhusheng Zhang1,2, Qiyuan Bao1,2, Yucheng Fu1,2
1Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Abstract:
(1) Background: The use of antiangiogenic TKIs (AA-TKIs) has recently emerged as a major paradigm shift in the treatment of advanced sarcoma. However, the feasibility of drug holidays for patients demonstrating a very favorable response remains unknown. (2) Methods: We aim to explore the outcomes of patients with advanced sarcoma who discontinued AA-TKIs after a (near-) complete remission or were long-term responders. Patients with advanced disease were included if they had bilateral or multiple lung metastases, extrapulmonary recurrence, a short disease-free interval, etc., at the initiation of AA-TKIs. (3) Results: A total of 22 patients with AA-TKI discontinuation were analyzed, with a median follow-up of 22.3 months post-discontinuation. Prior to discontinuation, there were four drug-induced complete remissions (CRs), twelve surgical CRs, and six long-term responders. Disease progression was observed in 17/22 (77.3%) patients, with a median of 4.2 months. However, since the majority were still sensitive to the original AA-TKIs and amenable to a second surgical remission, 7 out of these 17 patients achieved a second CR after disease progression and were thus considered as relapse-free post-discontinuation (pd-RFS). Therefore, the pd-RFS and post-discontinuation overall survival (pd-OS) in the last follow-up were 12/22 (54.5%) and 16/22 (72.7%), respectively. Remarkably, surgical CR and drug tapering off (versus abrupt stopping) were associated with a greater pd-RFS and pd-OS (p < 0.05). Furthermore, higher necrosis rates (p = 0.040) and lower neutrophil-to-lymphocyte ratios (NLR) (p = 0.060) before discontinuation tend to have a better pd-RFS. (4) Conclusions: Our results suggest that AA-TKI discontinuation with a taper-off strategy might be safe and feasible in highly selected patients with advanced sarcoma. Surgical CR, NLR, and tumor necrosis rates before discontinuation were potential biomarkers for AA-TKI withdrawal.
Insights
Discontinuing antiangiogenic tyrosine kinase inhibitors (AA-TKIs) may be safe for advanced sarcoma patients in remission. A taper-off strategy and surgical complete remission are linked to better outcomes and survival post-discontinuation.
Area of Science:
- Oncology
- Pharmacology
- Surgical Oncology
Background:
- Antiangiogenic tyrosine kinase inhibitors (AA-TKIs) represent a significant advancement in treating advanced sarcoma.
- The feasibility and outcomes of discontinuing AA-TKIs in patients achieving remission are not well-established.
Purpose of the Study:
- To investigate the outcomes of advanced sarcoma patients who discontinued AA-TKIs after achieving remission or as long-term responders.
- To identify potential predictive biomarkers for successful AA-TKI withdrawal.
Main Methods:
- Retrospective analysis of 22 advanced sarcoma patients who discontinued AA-TKIs.
- Evaluation of post-discontinuation relapse-free survival (pd-RFS) and overall survival (pd-OS).
- Correlation of outcomes with discontinuation strategy (tapering vs. abrupt), prior remission type, and pre-discontinuation biomarkers (necrosis rate, neutrophil-to-lymphocyte ratio).
Main Results:
- Disease progression occurred in 77.3% of patients, but 7 out of 17 achieved a second complete remission (CR) after restarting AA-TKIs.
- Post-discontinuation relapse-free survival (pd-RFS) was 54.5% and post-discontinuation overall survival (pd-OS) was 72.7%.
- Surgical CR and a drug tapering strategy were associated with significantly better pd-RFS and pd-OS. Higher tumor necrosis rates and lower neutrophil-to-lymphocyte ratios (NLR) before discontinuation also correlated with better pd-RFS.
Conclusions:
- AA-TKI discontinuation, particularly using a taper-off approach, appears safe and feasible in select advanced sarcoma patients.
- Surgical CR, NLR, and tumor necrosis rates are potential biomarkers to guide AA-TKI withdrawal decisions.
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