Skip to main content
SpringerLink
Log in

Combination of Bevacizumab and Osimertinib in Patients with EGFR T790M-Mutated Non-small Cell Lung Cancer

  • Short Communication
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background

Osimertinib may improve the prognosis of patients with epidermal growth factor receptor (EGFR) T790M-mutated non-small cell lung cancer (NSCLC); however, to date, the efficacy and safety of osimertinib plus bevacizumab have not been elucidated.

Objective

We aimed to investigate the additional effect of bevacizumab plus osimertinib compared with osimertinib alone in NSCLC patients with EGFR T790M mutation.

Methods

In this study, 32 patients received osimertinib alone, while 20 patients received osimertinib plus bevacizumab. The median follow-up was 12 months. Overall survival (OS) and progression-free survival (PFS) were estimated and adverse events (AEs) were compared.

Results

The overall response rate (ORR) was higher in the combination group than in the osimertinib-alone group (70.0% vs. 43.8%), and the OS (12.8% ± 7.7% vs. 45.4% ± 12.0%; p = 0.038) and PFS (37.3% ± 11.9% vs. 55.3% ± 14.3%; p = 0.045) were also significantly improved in patients who underwent osimertinib plus bevacizumab. Furthermore, the incidence of hypertension was significantly higher in the combination arm when compared with osimertinib alone (p = 0.003), and the number of other AEs were not significantly increased by adding bevacizumab (all p > 0.05).

Conclusion

Concomitant use of bevacizumab and osimertinib in NSCLC patients with EGFR T790M mutation may have potential therapeutic effect than osimertinib alone. Further studies with a larger number of patients are warranted to confirm results of this study.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

    Article  Google Scholar 

  2. Shi Y, Au JS, Thongprasert S, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol. 2014;9:154–62.

    Article  CAS  Google Scholar 

  3. Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med. 2011;3:75ra26.

    Article  Google Scholar 

  4. Yang JC, Ahn MJ, Kim DW, et al. Osimertinib in pretreated T790M-positive advanced non-small-cell lung cancer: AURA study phase II extension component. J Clin Oncol. 2017;35:1288–96.

    Article  CAS  Google Scholar 

  5. Mok TS, Y-LW, M-JA, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376:629–40.

  6. Akamatsu H, Toi Y, Hayashi H, et al. Efficacy of osimertinib plus bevacizumab vs osimertinib in patients with EGFR T790M-mutated non-small cell lung cancer previously treated with epidermal growth factor receptor-tyrosine kinase inhibitor: West Japan Oncology Group 8715L phase 2 randomized clinical trial. JAMA Oncol. 2021;7:386–94.

    Article  Google Scholar 

  7. Naumov GN, Nilsson MB, Cascone T, et al. Combined vascular endothelial growth factor receptor and epidermal growth factor receptor (EGFR) blockade inhibits tumor growth in xenograft models of EGFR inhibitor resistance. Clin Cancer Res. 2009;15:3484–94.

    Article  CAS  Google Scholar 

  8. Rosell R, Dafni U, Felip E, et al. Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial. Lancet Respir Med. 2017;5:435–44.

    Article  CAS  Google Scholar 

  9. Saito H, Fukuhara T, Furuya N, et al. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019;20:625–35.

    Article  CAS  Google Scholar 

  10. Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS. Lung cancer. Lancet. 2021;398:535–54.

    Article  Google Scholar 

  11. Tan CS, Kumarakulasinghe NB, Huang YQ, et al. Third generation EGFR TKIs: current data and future directions. Mol Cancer. 2018;17:29.

    Article  Google Scholar 

  12. Shah R, Lester JF. Tyrosine kinase inhibitors for the treatment of EGFR mutation-positive non-small-cell lung cancer: a clash of the generations. Clin Lung Cancer. 2020;21:e216–28.

    Article  CAS  Google Scholar 

  13. Cho BC, Chewaskulyong B, Lee KH, et al. Osimertinib versus standard of care EGFR TKI as first-line treatment in patients with EGFRm advanced NSCLC: FLAURA Asian Subset. J Thorac Oncol. 2019;14:99–106.

    Article  CAS  Google Scholar 

  14. Zhou Q, Xu CR, Cheng Y, et al. Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): a multicenter phase 3 study. Cancer Cell. 2021;39:1279-91.e3.

    Article  CAS  Google Scholar 

  15. Lu ZQ, Cai J, Wang X, et al. Osimertinib combined with bevacizumab for leptomeningeal metastasis from EGFR-mutation non-small cell lung cancer: a phase II single-arm prospective clinical trial. Thorac Cancer. 2021;12:172–80.

    Article  CAS  Google Scholar 

  16. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378:113–25.

    Article  CAS  Google Scholar 

  17. Cheng Y, He Y, Li W, et al. Osimertinib Versus comparator EGFR TKI as first-line treatment for EGFR-mutated advanced NSCLC: FLAURA China. A randomized study. Target Oncol. 2021;16:165–76.

    Article  Google Scholar 

  18. Jcf Q, Wang J, Sibley AB, et al. Bevacizumab-induced hypertension and proteinuria: a genome-wide study of more than 1000 patients. Br J Cancer. 2022;126(2):265–74.

    Article  Google Scholar 

Download references

Author information

Author notes

  1. Sha Liu and Tao Pan contributed equally to this work as co-first authors.

Authors and Affiliations

  1. Department of Radiotherapy, The First Affiliated Hospital of Hainan Medical University, Haikou, 570216, China

    Sha Liu, Tao Pan, Ming-Kun Wang, Shuang Zhang & Ping Zhou

  2. Department of Respiratory Diseases, The First Affiliated Hospital of Hainan Medical University, Haikou, 570216, China

    Jie Wang

Authors
  1. Sha Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tao Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ming-Kun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shuang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ping Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ping Zhou.

Ethics declarations

Funding

This work was supported by the Scientific Research Project of Health and Family Planning Industry in Hainan Province, China (19A200036).

Conflict of interest

Sha Liu, Tao Pan, Ming-Kun Wang, Jie Wang, Shuang Zhang, and Ping Zhou have no conflicts of interest to declare.

Ethics approval

All procedures in this study were in accordance with the 1964 Helsinki declaration. The protocol was approved by the Ethics Committee and Institutional Review Board of The First Affiliated Hospital of Hainan Medical University.

Consent to participate

Informed consent was obtained from all subjects enrolled in this study.

Consent for publication

Not applicable.

Availability of data and material

The data generated and analyzed during the current study are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

Authors’ contributions

SL and PZ were involved in the study conception and design; TP, MKW, and JW collected the data; and SZ and SL analyzed and interpreted the data. All authors read and approved the final version of the manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, S., Pan, T., Wang, MK. et al. Combination of Bevacizumab and Osimertinib in Patients with EGFR T790M-Mutated Non-small Cell Lung Cancer. Clin Drug Investig 42, 459–464 (2022). https://doi.org/10.1007/s40261-022-01145-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40261-022-01145-7

Search

Navigation