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Treatment efficacy of HER2-mutant lung adenocarcinoma by immune checkpoint inhibitors: a multicenter retrospective study

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Abstract

Background

Despite the remarkable clinical advance of immune checkpoint inhibitors (ICIs) in the treatment of lung cancer, there are limited studies focused on evaluating efficacy of ICIs for patients with human epidermal growth factor receptor 2 (HER2)-mutant lung adenocarcinoma.

Methods

We conducted a multicenter retrospective study of patients with HER2-mutant lung adenocarcinoma who received ICIs therapy at Shanghai Pulmonary Hospital, Shanghai Chest Hospital and the First Affiliated Hospital of Wenzhou Medical University between 2016 and 2021. Response was defined with reference to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.

Results

Among the 26 patients enrolled in our study, the overall objective response rate (ORR) was 38.5%, disease control rate (DCR) was 84.6% and median progression-free survival (PFS) was 7.4 months. Majority of patients were treated with immunochemotherapy combination regimens (16/26, 61.5%), with a median PFS of 8.4 months. Among the 9 patients receiving ICIs-based therapy as first-line treatment, 5 patients had partial response (PR) and 4 patients had stable disease (SD), with a median PFS of 9.1 months. Of the entire cohort, 5 patients who received ICIs before epidermal growth factor receptor (EGFR)/HER2-targeting drugs achieved a median PFS of 8.4 months.

Conclusion

Our retrospective study provides clinical evidence that front line of ICIs-based therapy is also worth considering for the treatment to improve survival outcomes of patients with HER2-mutant lung adenocarcinoma.

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Data availability material

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Abbreviations

CI:

Confidence interval

DCR:

Disease control rate

HER2:

Human epidermal growth factor receptor 2

ICIs:

Immune checkpoint inhibitors

PD-L1:

Programmed cell death ligand 1

NSCLC:

Non-small-cell lung cancer

ORR:

Objective response rate

PD-1:

Programmed cell death protein 1

PFS:

Progression-free survival

References

  1. Zhou C, Wu Y-L, Chen G et al (2011) Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 12(8):735–742

    Article  CAS  Google Scholar 

  2. Stephens P, Hunter C, Bignell G et al (2004) Lung cancer: Intragenic ERBB2 kinase mutations in tumours. Nature 431:525–526

    Article  CAS  Google Scholar 

  3. Sonobe M, Manabe T, Wada H et al (2006) Lung adenocarcinoma harboring mutations in the ERBB2 kinase domain. J Mol Diagn 8(3):351–356

    Article  CAS  Google Scholar 

  4. Shigematsu H, Takahashi T, Nomura M et al (2005) Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 65:1642–1646

    Article  CAS  Google Scholar 

  5. Pillai RN, Behera M, Berry LD et al (2017) HER2 mutations in lung adenocarcinomas: a report from the lung cancer mutation consortium. Cancer 123(21):4099–4105

    Article  CAS  Google Scholar 

  6. Zhou C, Li X, Wang Q et al (2020) Pyrotinib in HER2-mutant advanced lung adenocarcinoma after platinum-based chemotherapy: a multicenter, open-label, single-arm. Phase II Study J Clin Oncol 38(24):1753–2761

    Google Scholar 

  7. Tsurutani J, Iwata H, Krop I et al (2020) Targeting HER2 with trastuzumab deruxtecan: a dose-expansion, phase I study in multiple advanced solid tumors. Cancer Discov 10(5):688–701

    Article  CAS  Google Scholar 

  8. Mok. TSK, Wu. Y-L, Kudaba. I, et al., (2019) Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial Lancet, 393(1083): 1819–1830.

  9. Reck M, Rodriguez-Abreu D, Robinson AG et al (2016) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375(19):1823–1833

    Article  CAS  Google Scholar 

  10. Addeo A, Passaro A, Malapelle U et al (2021) Immunotherapy in non-small cell lung cancer harbouring driver mutations. Cancer Treat Rev 96:102179

    Article  CAS  Google Scholar 

  11. E.A. Eisenhauer PT, J. Bogaerts, L.H. Schwartz, D. Sargent, R. Ford, J. Dancey, S. Arbuck, S. Gwyther, M. Mooney, L. Rubinstein, L. Shankar, L. Dodd, and R. Kaplan DL, J. Verweij, (2009) New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer, 45(2): 228-47

  12. Mazières J, Barlesi F, Filleron T et al (2016) Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort. Ann Oncol 27(2):281–6

    Article  Google Scholar 

  13. Mazieres J, Drilon A, Lusque A et al (2019) Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol 30(8):1321–1328

    Article  CAS  Google Scholar 

  14. Rolfo C, Russo A (2020) HER2 mutations in non-small cell lung cancer: a herculean effort to hit the target. Cancer Discov 10(5):643–645

    Article  CAS  Google Scholar 

  15. Guisier F, Dubos-Arvis C, Vinas F et al (2020) Efficacy and Safety of Anti-PD-1 immunotherapy in patients with advanced NSCLC With BRAF, HER2, or MET mutations or RET translocation: GFPC 01–2018. J Thorac Oncol 15(4):628–636

    Article  CAS  Google Scholar 

  16. Lau SCM, Fares AF, Le LW et al (2021) Subtypes of EGFR- and HER2-mutant metastatic NSCLC influence response to immune checkpoint inhibitors. Clin Lung Cancer 22(4):253–259

    Article  CAS  Google Scholar 

  17. Saalfeld FC, Wenzel C, Christopoulos P, et al., (2021) Brief Report: Efficacy of immune checkpoint inhibitors alone or in combination with chemotherapy in NSCLC harboring ERBB2 mutations. J Thorac Oncol,.

  18. Zhao S, Xian X, Tian P et al (2021) Efficacy of combination chemo-immunotherapy as a first-line treatment for advanced non-small-cell lung cancer patients with HER2 alterations: a case series. Front Oncol 11:633522

    Article  Google Scholar 

  19. Emens LA, Middleton G (2015) The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res 3(5):436–443

    Article  CAS  Google Scholar 

  20. Huang MY, Jiang XM, Wang BL et al (2021) Combination therapy with PD-1/PD-L1 blockade in non-small cell lung cancer: strategies and mechanisms. Pharmacol Ther 219:107694

    Article  CAS  Google Scholar 

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Acknowledgements

Tianqing Chu, Jinyan Ye, Xing Li, Chao Zhao and Xiangling Chu collected the relevant data; Xiangling Chu, Huiping Qiang and Mengqing Xie drafted the manuscript text; Xiangling Chu and Xing Li performed statistical analyses; Jing Zhao, Yan Wu, Juan Zhou and Chaonan Han gave critical comments; Chunxia Su designed this study; Chunxia Su and Tianqing Chu revised the paper. All authors approved the final version of the manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (grant number: 82072568, 81874036), Shanghai Hospital Development Center (grant number: SHDC12020110) and Shanghai Anticancer Association (grant number: SACA-CY19B06).

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Author notes

  1. Xiangling Chu, Huiping Qiang and Mengqing Xie have contributed equally.

Authors and Affiliations

  1. Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, School of Medicine, Tongji University, Shanghai, China

    Xiangling Chu, Mengqing Xie, Jing Zhao, Yan Wu, Juan Zhou, Chaonan Han & Chunxia Su

  2. Department of Respiratory Medicine, Shanghai Chest Hospital, Jiaotong University, Shanghai, China

    Huiping Qiang & Tianqing Chu

  3. Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China

    Xing Li

  4. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Jinyan Ye

  5. Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China

    Chao Zhao

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  1. Xiangling Chu
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Correspondence to Tianqing Chu or Chunxia Su.

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Chu, X., Qiang, H., Xie, M. et al. Treatment efficacy of HER2-mutant lung adenocarcinoma by immune checkpoint inhibitors: a multicenter retrospective study. Cancer Immunol Immunother 71, 1625–1631 (2022). https://doi.org/10.1007/s00262-021-03100-5

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  • DOI: https://doi.org/10.1007/s00262-021-03100-5

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