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Anlotinib combined with PD-1 blockade for the treatment of lung cancer: a real-world retrospective study in China

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Abstract

Background

This study evaluated the efficacy and safety of anlotinib combined with programmed cell death protein 1 (PD-1) blockade for the treatment of small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC).

Patients and methods

SCLC (n = 28) and NSCLC (n = 177) patients who received treatment at Hunan Cancer Hospital between June 1, 2019, and July 1, 2020, were retrospectively analyzed. Progression-free survival (PFS) and treatment responses were compared among patients who received combination therapy of anlotinib plus PD-1 inhibitor, or monotherapy of either chemotherapy or PD-1 inhibitor. Independent prognostic factors were identified by Cox regression analysis.

Results

Patients with relapsed SCLC who received anlotinib plus PD-1 inhibitor as a ≥ second-line therapy (n = 14) had a significantly longer PFS than those who received PD-1 inhibitor alone (n = 14, 5.0 vs. 3.0 months; P = 0.005). For patients with previously untreated wild-type NSCLC, the combination therapy in the first-line setting (n = 6) provided a marginally longer PFS than mono-chemotherapy (n = 6, 8.0 vs. 3.0 months; P = 0.075). For patients with relapsed NSCLC, the combination therapy in the  ≥ second-line setting (n = 62) resulted in significantly higher objective response rate (19.3 vs. 5.0 vs. 2.4%; P = 0.013) and longer PFS (8.0 vs. 2.0 vs. 2.0 months; P <0.001) as compared to monotherapy of either chemotherapy (n = 41) or PD-1 inhibitor (n = 62). Anlotinib and PD-1 blockade combination therapy was an independent predictive factor of longer PFS (P <0.001).

Conclusion

The combination of anlotinib and PD-1 inhibitor has promising efficacy and manageable toxicity as a second- or later-line treatment of relapsed NSCLC and possibly for relapsed SCLC.

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Data availability

Data generated from this study are included as figures and tables in the main text and as supplementary files.

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Funding

This work was funded by the Natural Science Foundation of China (grant number: 81760529), and the Natural Science Foundation of Hunan Province (grant numbers: 2018RS3106, 2018SK50901, kq1801102, 2019-TJ-N04, 2019JJ50357, 2019SK4010, 2020JJ5340, and 2020JJ3025). The funding agencies had no role in the study design, data collection, analysis, interpretation, manuscript writing, and decision to submit the article for publication.

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    Authors and Affiliations

    1. Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China

      Xiangyu Zhang, Liang Zeng, Yizhi Li, Haiyan Yang, Yongchang Zhang & Nong Yang

    2. Qinghai Provincial People’s Hospital, Xining, 810000, China

      Qinqin Xu

    3. Burning Rock Biotech, Guangzhou, 510300, China

      Analyn Lizaso & Xinru Mao

    4. Sir Run Run Shaw Hospital, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, China

      Ren’an Jin

    5. Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China

      Yu Zeng

    6. Cancer Hospital, University of Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China

      Qinglin Li

    7. Department of Radiotherapy, Qilu Hospital of Shandong University, Jinan City, Shandong, China

      Jianbo Wang

    8. Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China

      Yang Li

    9. Graduate School, University of South China, Hengyang, 421001, Hunan, China

      Yongchang Zhang & Nong Yang

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    Author contribution

    YZ conceptualized, supervised and acquired funding for the study. XZ, LZ, YL curated and analyzed the clinical data and wrote the original manuscript draft. QX, HY, RJ, YZ, QL and JW contributed to the curation and analysis of clinical data. AL and XM contributed to the analysis of the data and manuscript preparation. YL and NY gave critical comments and suggestions. all authors reviewed and approved the manuscript.

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    Correspondence to Yongchang Zhang or Nong Yang.

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    Analyn Lizaso and Xinru Mao are employed by Burning Rock Biotech. All the other authors declare no conflict of interest.

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    This study was approved by the Institutional Review Board of the Hunan Cancer Hospital (approval number: 2017YYQ-SSB-126). Informed consent

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    Clinical trials registration The ATHENA Study, NCT04322617.

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    Zhang, X., Zeng, L., Li, Y. et al. Anlotinib combined with PD-1 blockade for the treatment of lung cancer: a real-world retrospective study in China. Cancer Immunol Immunother 70, 2517–2528 (2021). https://doi.org/10.1007/s00262-021-02869-9

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