Skip to main content

Advertisement

Log in

Switch maintenance therapy with anlotinib after chemotherapy in unresectable or metastatic soft tissue sarcoma: a single-center retrospective study

  • PRECLINICAL STUDIES
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

Background Chemotherapy is an important first-line treatment option in patients with advanced soft tissue sarcoma (STS). Whether maintenance therapy improves survival after chemotherapy is still controversial. Methods We retrospectively analyzed the data of 21 adults diagnosed with unresectable or metastatic STS between May 2018 and September 2019 in our center. They achieved an objective response or stable disease after chemotherapy and then received at least one cycle of switch maintenance therapy with anlotinib, a novel multi-targeted tyrosine kinase inhibitor. The objective response rate (ORR), disease control rate (DCR), adverse events, and median progression-free survival (PFS) after anlotinib maintenance (PFSa), and the median PFS after chemotherapy (PFSc) were analyzed. Results Nineteen patients received first-line chemotherapy and 2 received second-line chemotherapy. Five patients achieved a partial response and 16 had stable disease after chemotherapy. The median number of anlotinib maintenance cycles was five (range, 2–31). One patient achieved a complete response and two patients exhibited a partial response during anlotinib maintenance, with an ORR of 14.3%. The DCR was 81.0%. After a median follow-up of 14.0 months, the median PFSa and PFSc were 7.3 and 13.6 months, respectively. Grade 3/4 adverse events occurred in six (28.6%) patients and were managed through symptomatic treatment, dose reduction or anlotinib discontinuance. Conclusion Our results indicate that switch maintenance therapy with anlotinib is a promising strategy for the treatment of patients with unresectable or metastatic STS who have benefited from chemotherapy. Toxicities were manageable. Prospective clinical trials are needed to confirm this finding.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Data availability

The data and material are available for reasonable requests.

References

  1. Clark MA, Fisher C, Judson I, Thomas JM (2005) Soft-tissue sarcomas in adults. N Engl J Med 353:701–711. https://doi.org/10.1056/NEJMra041866

    Article  CAS  PubMed  Google Scholar 

  2. Nakano K, Takahashi S (2020) Precision medicine in soft tissue sarcoma treatment. Cancers (Basel) 12:221. https://doi.org/10.3390/cancers12010221

    Article  CAS  Google Scholar 

  3. Judson I, Verweij J, Gelderblom H, Hartmann JT, Schoffski P, Blay JY et al (2014) Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol 15:415–423. https://doi.org/10.1016/S1470-2045(14)70063-4

    Article  CAS  PubMed  Google Scholar 

  4. Lebellec L, Defachelles AS, Cren PY, Penel N (2020) Maintenance therapy and drug holiday in sarcoma patients: systematic review. Acta Oncol 59:1084–1090. https://doi.org/10.1080/0284186X.2020.1759825

    Article  CAS  PubMed  Google Scholar 

  5. Bisogno G, De Salvo GL, Bergeron C, Gallego Melcon S, Merks JH, Kelsey A et al (2019) Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 20:1566–1575. https://doi.org/10.1016/S1470-2045(19)30617-5

    Article  CAS  PubMed  Google Scholar 

  6. D'Adamo DR, Anderson SE, Albritton K, Yamada J, Riedel E, Scheu K et al (2005) Phase II study of doxorubicin and bevacizumab for patients with metastatic soft-tissue sarcomas. J Clin Oncol 23:7135–7142. https://doi.org/10.1200/JCO.2005.16.139

    Article  CAS  PubMed  Google Scholar 

  7. Bui N, Kamat N, Ravi V, Chawla S, Lohman M, Ganjoo KN (2018) A multicenter phase II study of Q3 week or weekly paclitaxel in combination with bevacizumab for the treatment of metastatic or unresectable angiosarcoma. Rare Tumors 10:2036361318771771. https://doi.org/10.1177/2036361318771771

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chawla SP, Cranmer LD, Van Tine BA, Reed DR, Okuno SH, Butrynski JE et al (2014) Phase II study of the safety and antitumor activity of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma. J Clin Oncol 32:3299–3306. https://doi.org/10.1200/JCO.2013.54.3660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D et al (2016) Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet 388:488–497. https://doi.org/10.1016/S0140-6736(16)30587-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tap WD, Papai Z, Van Tine BA, Attia S, Ganjoo KN, Jones RL et al (2017) Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. Lancet Oncol 18:1089–1103. https://doi.org/10.1016/S1470-2045(17)30381-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tap WD, Wagner AJ, Schoffski P, Martin-Broto J, Krarup-Hansen A, Ganjoo KN et al (2020) Effect of doxorubicin plus Olaratumab vs doxorubicin plus placebo on survival in patients with advanced soft tissue sarcomas: the ANNOUNCE randomized clinical trial. JAMA 323:1266–1276. https://doi.org/10.1001/jama.2020.1707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pautier P, Penel N, Ray-Coquard I, Italiano A, Bompas E, Delcambre C et al (2020) A phase II of gemcitabine combined with pazopanib followed by pazopanib maintenance, as second-line treatment in patients with advanced leiomyosarcomas: a unicancer French sarcoma group study (LMS03 study). Eur J Cancer 125:31–37. https://doi.org/10.1016/j.ejca.2019.10.028

    Article  CAS  PubMed  Google Scholar 

  13. Garcia Del Muro X, Maurel J, Martinez Trufero J, Lavernia J, Lopez Pousa A, de Las Penas R et al (2018) Phase II trial of ifosfamide in combination with the VEGFR inhibitor sorafenib in advanced soft tissue sarcoma: a Spanish group for research on sarcomas (GEIS) study. Investig New Drugs 36:468–475. https://doi.org/10.1007/s10637-018-0583-z

    Article  CAS  Google Scholar 

  14. Demetri GD, Chawla SP, Ray-Coquard I, Le Cesne A, Staddon AP, Milhem MM et al (2013) Results of an international randomized phase III trial of the mammalian target of rapamycin inhibitor ridaforolimus versus placebo to control metastatic sarcomas in patients after benefit from prior chemotherapy. J Clin Oncol 31:2485–2492. https://doi.org/10.1200/JCO.2012.45.5766

    Article  CAS  PubMed  Google Scholar 

  15. Sun Y, Niu W, Du F, Du C, Li S, Wang J et al (2016) Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors. J Hematol Oncol 9:105. https://doi.org/10.1186/s13045-016-0332-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chi Y, Fang Z, Hong X, Yao Y, Sun P, Wang G et al (2018) Safety and efficacy of Anlotinib, a multikinase angiogenesis inhibitor, in patients with refractory metastatic soft-tissue sarcoma. Clin Cancer Res 24:5233–5238. https://doi.org/10.1158/1078-0432.CCR-17-3766

    Article  CAS  PubMed  Google Scholar 

  17. Chi Y, Yao Y, Wang S, Huang G, Cai Q, Shang G et al (2018) Anlotinib for metastasis soft tissue sarcoma: A randomized, double-blind, placebo-controlled and multi-centered clinical trial. J Clin Oncol 36:suppl; abstr 11503. https://ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.11503. Accessed 21 Sept 2020.

  18. Wang HY, Chu JF, Zhang P, Wang JQ, Yan Z, Yao SN et al (2020) Safety and efficacy of chemotherapy combined with Anlotinib plus Anlotinib maintenance in Chinese patients with advanced/metastatic soft tissue sarcoma. Onco Targets Ther 13:1561–1568. https://doi.org/10.2147/OTT.S235349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Tian Z, Liu H, Zhang F, Li L, Du X, Li C et al (2020) Retrospective review of the activity and safety of apatinib and anlotinib in patients with advanced osteosarcoma and soft tissue sarcoma. Investig New Drugs 38:1559–1569. https://doi.org/10.1007/s10637-020-00912-7

    Article  Google Scholar 

Download references

Acknowledgments

We would like to thank Leo Gerweck, PhD, for language editing and proofreading.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

Authors

Contributions

Jie Liu and Yao-Tiao Deng contributed to the data curation, methodology, formal analysis, original draft and final revision. Yu Jiang contributed to the conceptualization, methodology, interpretation, project administration and final revision. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Yu Jiang.

Ethics declarations

Conflict of interest

All authors declare that no conflict of interest exists in this study.

Ethics approval

The study was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Individually informed consent was waived for this retrospective study.

Code availability

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, J., Deng, YT. & Jiang, Y. Switch maintenance therapy with anlotinib after chemotherapy in unresectable or metastatic soft tissue sarcoma: a single-center retrospective study. Invest New Drugs 39, 330–336 (2021). https://doi.org/10.1007/s10637-020-01015-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-020-01015-z

Keywords

Navigation