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Effect and outcomes analysis of anlotinib in non-small cell lung cancer patients with liver metastasis: results from the ALTER 0303 phase 3 randomized clinical trial

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Purpose

Liver metastasis (LM) is common in non-small cell lung cancer (NSCLC), and always predicted worse outcomes with no effective therapy. We aimed to evaluate the effects and prognosis in LM patients treated with anlotinib.

Methods

The present study is a post hoc analysis based on a multicenter, double-blind, phase 3 randomized clinical trial which designed to evaluate the efficacy and safety of anlotinib in patients with advanced NSCLC. A total of 437 patients were enrolled in present study, and 78 patients with LM.

Results

Patients with LM showed a worse outcome compared to those without LM (PFS median, 2.6 vs 4.2 months), and OS (median, 5.6 vs 9.4 months, both P < 0.0001). The anlotinib was associated with longer PFS (median, 3.0 months) compared with placebo (median, 0.9 months), with a hazard ratio (HR) of 0.23 (95%CI, 0.12–0.42; P < 0.0001). Furthermore, OS was marginally significantly better in anlotinib group (median 6.6 months), compared with placebo (median 4.0 months), HR 0.61 (95%CI, 0.36–1.02; P = 0.055). Multivariate analysis confirmed normal peripheral blood LDH/TBiL level predicted better PFS and OS, lower ECOG score acted as independently prognostic factor for superior OS. Anlotinib was more associated with hand–foot syndrome (7.7% vs 0) and serum TSH level rise (7.7% vs 3.8%) and well tolerated, all AEs were no more than grade 3.

Conclusion

Patients with LM had a dismal prognosis, anlotinib could lead to a better PFS in pretreated NSCLC patients, which suggested anlotinib is a potential third-line or further therapy in these patients.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all the patients who involved in this trial, and this work was supported by the “Star of SJTU” plan Medical-Engineering cross fund of Shanghai Jiao Tong University (YG2019QNA48), the Western Medicine Guide Project of the Shanghai Committee of Science and Technology (18411968500) and Medical innovation project of Scientific and Technological innovation action plan of the Shanghai Committee of Science and Technology (21Y11913500).

Funding

This work was supported by the “Star of SJTU” plan Medical-Engineering cross fund of Shanghai Jiao Tong University (YG2019QNA48), the Western Medicine Guide Project of the Shanghai Committee of Science and Technology (18411968500) and Medical innovation project of Scientific and Technological innovation action plan of the Shanghai Committee of Science and Technology (21Y11913500).

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Authors and Affiliations

  1. Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, West Huaihai Road 241, Xuhui district, Shanghai, 230032, China

    Yinchen Shen, Jun Lu, Fang Hu, Jialin Qian, Xueyan Zhang, Runbo Zhong, Hua Zhong, Tianqing Chu & Baohui Han

Authors
  1. Yinchen Shen
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  2. Jun Lu
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  3. Fang Hu
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  4. Jialin Qian
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  5. Xueyan Zhang
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  6. Runbo Zhong
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  7. Hua Zhong
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  8. Tianqing Chu
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  9. Baohui Han
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Contributions

All authors have made substantial contributions to the conception and design of the study. YCS, JL and FH contributed to data extraction, quality assessment, statistical analysis, and writing the report. JLQ, XYZ, RBZ and HZ contributed to data extraction and quality assessment. YCS, JL, FH, TQC and BHH contributed to interpretation of data and revision of the report. All authors reviewed and approved the final version of the manuscript.

Corresponding authors

Correspondence to Tianqing Chu or Baohui Han.

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Conflict of interest

The authors have declared that no competing interests exist.

Ethics approval

The clinical trial was approved by the independent ethics committee of each trial center and was carried out in accordance with the Declaration of Helsinki and Good Clinical Practice requirements.

Consent to participate

All patients provided written informed consent in this study.

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Supplementary Information

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Supplement Figure 1

Progression-Free (A) and Overall Survival (B) of different histology type tumors in LM patients Supplementary file1 (TIFF 419 KB)

Supplement Figure 2

Overall Survival of different peripheral blood AST level (A) and ECOG PS score (B) in LM patients Supplementary file2 (TIFF 388 KB)

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Shen, Y., Lu, J., Hu, F. et al. Effect and outcomes analysis of anlotinib in non-small cell lung cancer patients with liver metastasis: results from the ALTER 0303 phase 3 randomized clinical trial. J Cancer Res Clin Oncol 149, 1417–1424 (2023). https://doi.org/10.1007/s00432-022-03964-9

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  • DOI: https://doi.org/10.1007/s00432-022-03964-9

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