Lenvatinib Monotherapy Versus Lenvatinib in Combination with PD-1 Blockades as Re-Challenging Treatment for Patients with Metastatic Osteosarcoma: A Real-World Study.

IF 5.1 2区医学 Q1 CHEMISTRY, MEDICINAL Drug Design, Development and Therapy Pub Date : 2025-02-18 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S501742

Guohui Song, Qinglian Tang, Jinchang Lu, Huaiyuan Xu, Anqi Wang, Chuangzhong Deng, Hao Wu, Jinxin Hu, Xiaojun Zhu, Jin Wang

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Abstract

Purpose: To explore the efficacy and safety of lenvatinib, either as a monotherapy or in combination with programmed death-1 (PD-1) blockades, as re-challenging treatment in patients with metastatic osteosarcoma following treatment failure with previous tyrosine kinase inhibitors (TKIs).

Patients and methods: We retrospectively reviewed the data of 26 patients with metastatic osteosarcoma who received rechallenge treatment with lenvatinib monotherapy or lenvatinib plus PD-1 blockades after failure of the initial TKI treatment from January 2020 to June 2024 in our center. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), and safety.

Results: Of the 26 patients, ORR and CBR were 11.5% and 61.5%, respectively. The median duration of follow-up was 15 months (range, 4.3-25.6) with a median PFS of 7.2 months (95% CI: 1.9-12.5). A total of 14 patients received lenvatinib as a monotherapy, and 12 received a combination therapy of lenvatinib and PD-1 blockade. No significant differences were observed in ORR (0 vs 25%) and CBR (57.1 vs 66.7%) between the two groups. Additionally, the combination cohort exhibited a significantly longer PFS compared to the monotherapy cohort (8.6 [95% CI: 5.0-12.1] vs 4.0 months [95% CI: 1.0-7.0], p = 0.022). 96.2% of patients experienced grade 1 or more adverse events (AEs). Grade 3 adverse events occurred in 6 (23.1%) patients. The safety profiles of the lenvatinib and PD-1 blockade combination group were found to be comparable to those of the lenvatinib monotherapy group.

Conclusion: Our data indicated that patients with metastatic osteosarcoma could potentially benefit from lenvatinib rechallenge after progress with initial TKI treatment. The combination of lenvatinib and PD-1 blockade therapy demonstrated promising survival outcomes in patients with metastatic osteosarcoma, accompanied by a manageable toxicity profile.

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Lenvatinib单药治疗与Lenvatinib联合PD-1阻断剂作为转移性骨肉瘤患者的再挑战治疗：一项真实世界的研究

目的：探讨lenvatinib作为单一疗法或与程序性死亡-1 （PD-1）抑制剂联合治疗转移性骨肉瘤患者在先前使用酪氨酸激酶抑制剂（TKIs）治疗失败后的再挑战治疗的有效性和安全性。患者和方法：我们回顾性回顾了本中心2020年1月至2024年6月26例转移性骨肉瘤患者的数据，这些患者在初始TKI治疗失败后接受lenvatinib单药治疗或lenvatinib加PD-1阻断治疗。主要终点为无进展生存期（PFS）。次要终点包括客观缓解率（ORR）、临床获益率（CBR）和安全性。结果：26例患者的ORR和CBR分别为11.5%和61.5%。中位随访时间为15个月（范围4.3-25.6），中位PFS为7.2个月（95% CI: 1.9-12.5）。共有14例患者接受lenvatinib单药治疗，12例患者接受lenvatinib联合PD-1阻断治疗。两组间ORR （0 vs 25%）和CBR （57.1 vs 66.7%）无显著差异。此外，联合治疗组的PFS明显长于单药治疗组（8.6个月[95% CI: 5.0-12.1] vs 4.0个月[95% CI: 1.0-7.0], p = 0.022）。96.2%的患者出现1级或以上不良事件（ae）。6例（23.1%）患者发生3级不良事件。发现lenvatinib和PD-1阻断联合组的安全性与lenvatinib单药治疗组相当。结论：我们的数据表明，转移性骨肉瘤患者在初始TKI治疗取得进展后，可能从lenvatinib再挑战中获益。lenvatinib联合PD-1阻断治疗在转移性骨肉瘤患者中显示出有希望的生存结果，并伴有可控的毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.