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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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Lenvatinib in Combination with PD-1 Blockades as Re-Challenging Treatment for Patients with Metastatic Soft Tissue

Guohui Song1,2, Jinxin Hu1,2, Wenqian He1,2

  • 1Department of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.

Drug Design, Development and Therapy
|April 6, 2026
PubMed
Abstract

Insights

This study found that combining lenvatinib with programmed death-1 (PD-1) blockades offers potential benefits for metastatic soft tissue sarcoma (STS) patients who failed prior tyrosine kinase inhibitors (TKIs). The re-challenge therapy showed encouraging survival outcomes and a manageable safety profile.

Area of Science:

  • Oncology
  • Medical Research
  • Pharmacology

Background:

  • Lenvatinib and PD-1 blockades are effective sarcoma treatments.
  • Limited data exists on combining lenvatinib with PD-1 blockades as re-challenge therapy for metastatic STS after TKI failure.

Purpose of the Study:

  • To evaluate the efficacy and safety of lenvatinib plus PD-1 blockades as re-challenge therapy in metastatic STS patients.
  • To assess progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety.

Main Methods:

  • Retrospective analysis of 28 metastatic STS patients treated with lenvatinib and PD-1 blockades after prior TKI progression.
  • Primary endpoint: PFS. Secondary endpoints: ORR, CBR, OS, and safety.

Main Results:

  • Median PFS was 4.8 months; median OS was 23 months.
  • CBR was 64.3%; ORR was 0%.
  • 96.4% experienced any-grade adverse events; 17.9% had Grade 3 adverse events.

Conclusions:

  • Combination therapy of lenvatinib and PD-1 blockades may benefit metastatic STS patients post-TKI failure.
  • The re-challenge approach demonstrated encouraging survival results.
  • The safety profile of this combination therapy was deemed acceptable and manageable.
Keywords:
PD-1 blockadeslenvatinibmetastatic soft tissue sarcomarechallengetyrosine kinase inhibitor

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