Multi-targeted tyrosine kinase inhibitors as third-line regimen in advanced non-small cell lung cancer: a network
Zhonghan Zhang1, Yuanyuan Zhao1, Feiteng Lu1
1Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
Background:
Four multi-targeted tyrosine kinase inhibitors (TKIs) including apatinib, anlotinib, fruquintinib and lenvatinib are currently available as third-line regimen for advanced non-small cell lung cancer (NSCLC) patients who failed at least two lines of systemic therapy. Limited evidence was provided to demonstrate the general efficacy and safety profile of these drugs as third-line treatment approach for NSCLC.
Methods:
Eligible literature was searched from electronic database. Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), treatment related adverse event (TRAE), treatment related adverse event grade 3-5 (TRAE3-5), hypertension, proteinuria, hand-foot skin reaction (HFSR), elevated ALT/AST, nausea and vomiting, diarrhea were synthetically extracted. Multiple-treatments comparisons (MTCs) based on a Bayesian consistency model integrated the efficacy and toxicity outcomes. Rank probabilities of each regimen were assessed and clustered by the surface under the cumulative ranking curve.
Results:
Five phase II/III randomized trials involving 915 advanced NSCLC patients were enrolled. MTCs showed that four multi-targeted TKIs shared equivalent efficacy in terms of outcome measures, of which anlotinib stood out in ORR (OR =39.26; 95% CI: 2.36-2,748.06), DCR (OR =8.69; 95% CI: 1.70-50.18) and PFS (HR =0.27; 95% CI: 0.10-0.78) when compared with placebo plus BSC. No significantly differences were observed among these TKIs and placebo with respect to OS, TRAE and TRAE 3-5. Fruquintinib and lenvatinib may relate to high rate of HFSR while anlotinib may relate to hypertension.
Conclusions:
Multi-targeted TKIs (apatinib, anlotinib, fruquintinib and lenvatinib) with acceptable efficacy and safety profile were options for advanced NSCLC in third-line setting.
Insights
Four multi-targeted tyrosine kinase inhibitors (TKIs) offer an effective third-line treatment for advanced non-small cell lung cancer (NSCLC). Anlotinib showed superior objective response rate, disease control rate, and progression-free survival compared to placebo.
Area of Science:
- Oncology
- Pharmacology
Background:
- Advanced non-small cell lung cancer (NSCLC) patients often require third-line systemic therapy after failing prior treatments.
- Four multi-targeted tyrosine kinase inhibitors (TKIs) – apatinib, anlotinib, fruquintinib, and lenvatinib – are available for this patient group.
- Limited comparative data exists on the efficacy and safety of these TKIs in the third-line setting for NSCLC.
Purpose of the Study:
- To compare the efficacy and safety of four multi-targeted TKIs (apatinib, anlotinib, fruquintinib, lenvatinib) as a third-line treatment for advanced NSCLC.
- To provide evidence-based guidance for selecting optimal third-line TKI therapy in advanced NSCLC.
Main Methods:
- A systematic literature search identified eligible phase II/III randomized trials.
- Bayesian multiple-treatments comparisons (MTCs) integrated efficacy outcomes (ORR, DCR, PFS, OS) and toxicity data (TRAE, hypertension, HFSR, etc.).
- Rank probabilities were assessed using the surface under the cumulative ranking curve (SUCRA).
Main Results:
- Five trials with 915 patients were analyzed, showing comparable overall efficacy among the four TKIs.
- Anlotinib demonstrated superior objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) versus placebo.
- No significant differences in overall survival (OS), treatment-related adverse events (TRAE), or severe TRAEs were observed. Fruquintinib and lenvatinib were associated with higher hand-foot skin reaction (HFSR) rates, while anlotinib was linked to hypertension.
Conclusions:
- Multi-targeted TKIs, including apatinib, anlotinib, fruquintinib, and lenvatinib, represent viable third-line treatment options for advanced NSCLC.
- These TKIs offer acceptable efficacy and safety profiles for patients who have failed prior therapies.
- Anlotinib shows potential advantages in specific efficacy endpoints, warranting consideration in clinical practice.
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