Efficacy and safety of apatinib for patients with advanced extremity desmoid fibromatosis: a retrospective study

Abstract

Purpose

Desmoid fibromatosis (DF) is a locally aggressive connective-tissue tumor arising in deep soft tissues. Although multiple therapeutic modalities have been demonstrated effective for DF, there is no standard systemic treatment for progressive and recurrent DF. As a part of systemic treatment, tyrosine kinase inhibitors have shown promising activity against DF with tolerable toxicity profiles. Thus, the aim of this study was to investigate the efficacy and safety of apatinib, a novel multi-target angiogenesis inhibitor, in patients with DF.

Methods

We retrospectively analyzed the medical records of patients with advanced extremity DF regularly treated with apatinib between October 2017 and January 2020 in our center. Apatinib was initially administered with a dose of 250 mg daily and the dose was adjusted according to the toxicity. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors 1.1 criteria. The primary endpoint was progression-free survival (PFS); objective response rates and drug-related adverse events were also evaluated.

Results

A total of 22 (6 male, 16 female) patients with advanced extremity DF were included. The mean medication time was 17 months. None of the patients reached a complete response, but ten (45.5%) patients achieved partial response, and 11 patients (50%) achieved stable disease. One (4.5%) patient developed progressive disease, and the 1-year PFS rate was 95.2%. The disease control rate was 95.4% (21/22) and the objective response rate was 45.5% (10/22). Meanwhile, 18 (81.8%) patients with a tumor shrinkage were accompanied by a decreased signal intensity of lesions in T2-weighted magnetic resonance imaging. The most frequent adverse events included hand-foot syndrome (n = 7, 31.8%), fatigue (n = 6, 27.2%), local pain (n = 4, 18.1%), diarrhea (n = 4, 18.1%).

Conclusion

Apatinib is an effective and well-tolerated option for patients with advanced extremity DF. Indeed, further prospective, randomized studies with larger cases are required to fully explore the clinical utility of apatinib in DF.

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Data availability

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

References

  1. Bonvalot S et al (2008) Extra-abdominal primary fibromatosis: aggressive management could be avoided in a subgroup of patients European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of. Surg Oncol 34:462–468. https://doi.org/10.1016/j.ejso.2007.06.006

    CAS  Article  Google Scholar 

  2. Briand S, Barbier O, Biau D, Bertrand-Vasseur A, Larousserie F, Anract P, Gouin F (2014) Wait-and-see policy as a first-line management for extra-abdominal desmoid tumors. J Bone Jt Surg Am 96:631–638. https://doi.org/10.2106/jbjs.M.00988

    Article  Google Scholar 

  3. Chugh R et al (2010a) Efficacy of imatinib in aggressive fibromatosis: results of a phase II multicenter Sarcoma Alliance for Research through Collaboration (SARC) trial. Clin Cancer Res 16:4884–4891. https://doi.org/10.1158/1078-0432.Ccr-10-1177

    CAS  Article  PubMed  Google Scholar 

  4. Eisenhauer EA et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    CAS  Article  Google Scholar 

  5. Elnekave E et al (2018) Doxorubicin-eluting intra-arterial therapy for pediatric extra-abdominal desmoid fibromatoses: a promising approach for a perplexing disease. J Vasc Interv Radiol 29:1376–1382. https://doi.org/10.1016/j.jvir.2018.04.009

    Article  PubMed  Google Scholar 

  6. Fiore M et al (2009) Desmoid-type fibromatosis: a front-line conservative approach to select patients for surgical treatment. Ann Surg Oncol 16:2587–2593. https://doi.org/10.1245/s10434-009-0586-2

    Article  PubMed  Google Scholar 

  7. Fiore M et al (2015) Hormonal manipulation with toremifene in sporadic desmoid-type fibromatosis. Eur J Cancer 51:2800–2807. https://doi.org/10.1016/j.ejca.2015.08.026

    CAS  Article  PubMed  Google Scholar 

  8. Ganeshan D, Amini B, Nikolaidis P, Assing M, Vikram R (2019) Current update on desmoid fibromatosis. J Comput Assist Tomogr 43:29–38. https://doi.org/10.1097/RCT.0000000000000790

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gluck I, Griffith KA, Biermann JS, Feng FY, Lucas DR, Ben-Josef E (2011) Role of radiotherapy in the management of desmoid tumors. Int J Radiat Oncol Biol Phys 80:787–792. https://doi.org/10.1016/j.ijrobp.2010.02.053

    Article  PubMed  Google Scholar 

  10. Gondim Teixeira PA, Biouichi H, Abou Arab W, Rios M, Sirveaux F, Hossu G, Blum A (2020) Evidence-based MR imaging follow-up strategy for desmoid-type fibromatosis. Eur Radiol 30:895–902. https://doi.org/10.1007/s00330-019-06404-4

    CAS  Article  PubMed  Google Scholar 

  11. Gounder MM et al (2011) Activity of Sorafenib against desmoid tumor/deep fibromatosis. Clin Cancer Res 17:4082–4090. https://doi.org/10.1158/1078-0432.Ccr-10-3322

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Gounder MM et al (2018) Sorafenib for advanced and refractory desmoid tumors. N Engl J Med 379:2417–2428. https://doi.org/10.1056/NEJMoa1805052

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Gronchi A et al (2003) Quality of surgery and outcome in extra-abdominal aggressive fibromatosis: a series of patients surgically treated at a single institution. J Clin Oncol 21:1390–1397. https://doi.org/10.1200/JCO.2003.05.150

    CAS  Article  PubMed  Google Scholar 

  14. Gronchi A et al (2014) Sporadic desmoid-type fibromatosis: a stepwise approach to a non-metastasising neoplasm–a position paper from the Italian and the French Sarcoma Group. Ann Oncol 25:578–583. https://doi.org/10.1093/annonc/mdt485

    CAS  Article  PubMed  Google Scholar 

  15. Heinrich MC et al (2006) Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor). J Clin Oncol 24:1195–1203. https://doi.org/10.1200/jco.2005.04.0717

    CAS  Article  PubMed  Google Scholar 

  16. Karcioglu O, Topacoglu H, Dikme O, Dikme O (2018) A systematic review of the pain scales in adults: Which to use? Am J Emerg Med 36:707–714. https://doi.org/10.1016/j.ajem.2018.01.008

    Article  PubMed  Google Scholar 

  17. Kasper B et al (2015) Management of sporadic desmoid-type fibromatosis: a European consensus approach based on patients’ and professionals’ expertise—a sarcoma patients EuroNet and European Organisation for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group initiative. Eur J Cancer 51:127–136. https://doi.org/10.1016/j.ejca.2014.11.005

    CAS  Article  PubMed  Google Scholar 

  18. Kasper B et al (2017a) An update on the management of sporadic desmoid-type fibromatosis: a European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG). Ann Oncol 28:2399–2408. https://doi.org/10.1093/annonc/mdx323

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Kasper B et al (2017b) Imatinib induces sustained progression arrest in RECIST progressive desmoid tumours: final results of a phase II study of the German Interdisciplinary Sarcoma Group (GISG). Eur J Cancer 76:60–67. https://doi.org/10.1016/j.ejca.2017.02.001

    CAS  Article  PubMed  Google Scholar 

  20. Keus RB et al (2013) Results of a phase II pilot study of moderate dose radiotherapy for inoperable desmoid-type fibromatosis–an EORTC STBSG and ROG study (EORTC 62991–22998). Ann Oncol 24:2672–2676. https://doi.org/10.1093/annonc/mdt254

    CAS  Article  PubMed  Google Scholar 

  21. Liao Z et al (2019) Phase II trial of VEGFR2 inhibitor apatinib for metastatic sarcoma: focus on efficacy and safety. Exp Mol Med 51:1–11. https://doi.org/10.1038/s12276-019-0221-7

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Liu X et al (2020) Efficacy and safety of the VEGFR2 inhibitor Apatinib for metastatic soft tissue sarcoma: Chinese cohort data from NCT03121846. Biomed Pharmacother 122:109587. https://doi.org/10.1016/j.biopha.2019.109587

    CAS  Article  PubMed  Google Scholar 

  23. Luo J et al (2019) Single institution experience of split course radiotherapy in patients with desmoid tumors. Onco Targets Ther 12:1741–1748. https://doi.org/10.2147/OTT.S189449

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Organization WH, Cancer IAfRo (2013) WHO classification of tumours of soft tissue and bone.

  25. Palassini E et al (2017) Long-term efficacy of methotrexate plus vinblastine/vinorelbine in a large series of patients affected by desmoid-type fibromatosis. Cancer journal (Sudbury, Mass) 23:86–91. https://doi.org/10.1097/ppo.0000000000000254

    CAS  Article  Google Scholar 

  26. Penel N et al (2011) Imatinib for progressive and recurrent aggressive fibromatosis (desmoid tumors): an FNCLCC/French Sarcoma Group phase II trial with a long-term follow-up. Ann Oncol 22:452–457. https://doi.org/10.1093/annonc/mdq341

    CAS  Article  PubMed  Google Scholar 

  27. Penel N et al (2016) Management of desmoid tumours: a nationwide survey of labelled reference centre networks in France. Eur J Cancer 58:90–96. https://doi.org/10.1016/j.ejca.2016.02.008

    Article  PubMed  Google Scholar 

  28. Sheth PJ et al (2016) Desmoid fibromatosis: MRI features of response to systemic therapy. Skeletal Radiol 45:1365–1373. https://doi.org/10.1007/s00256-016-2439-y

    Article  PubMed  Google Scholar 

  29. Skubitz KM (2017) Biology and treatment of aggressive fibromatosis or desmoid tumor. Mayo Clin Proc 92:947–964. https://doi.org/10.1016/j.mayocp.2017.02.012

    Article  PubMed  Google Scholar 

  30. Stacchiotti S et al (2009) High-grade soft-tissue sarcomas: tumor response assessment–pilot study to assess the correlation between radiologic and pathologic response by using RECIST and Choi criteria. Radiology 251:447–456. https://doi.org/10.1148/radiol.2512081403

    Article  PubMed  Google Scholar 

  31. Szucs Z et al (2017) Pazopanib, a promising option for the treatment of aggressive fibromatosis. Anticancer Drugs 28:421–426. https://doi.org/10.1097/CAD.0000000000000474

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. Tian S et al (2011) YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci 102:1374–1380. https://doi.org/10.1111/j.1349-7006.2011.01939.x

    CAS  Article  PubMed  Google Scholar 

  33. Toulmonde M et al (2019) Pazopanib or methotrexate-vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): a non-comparative, randomised, open-label, multicentre, phase 2 study. Lancet Oncol 20:1263–1272. https://doi.org/10.1016/s1470-2045(19)30276-1

    CAS  Article  PubMed  Google Scholar 

  34. Wang YF, Guo W, Sun KK, Yang RL, Tang XD, Ji T, Tang S (2015) Postoperative recurrence of desmoid tumors: clinical and pathological perspectives. World J Surg Oncol 13:26. https://doi.org/10.1186/s12957-015-0450-8

    Article  PubMed  PubMed Central  Google Scholar 

  35. Wang Y et al (2019a) The efficacy and safety of apatinib in metastatic alveolar soft part sarcoma: a case series of six patients in one institution. Cancer Manag Res 11:3583–3591. https://doi.org/10.2147/CMAR.S198429

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. Wang Z, Wu J, Tian X, Hao C (2019b) Targeted therapy of desmoid-type fibromatosis: mechanism, current situation, and future prospects. Front Med 13:427–437. https://doi.org/10.1007/s11684-018-0672-6

    Article  PubMed  Google Scholar 

  37. Wang Y et al (2020) The efficacy and safety of apatinib in advanced synovial sarcoma: a case series of twenty-one patients in one single institution. Cancer Manag Res 12:5255–5264. https://doi.org/10.2147/CMAR.S254296

    CAS  Article  Google Scholar 

  38. Wilhelm SM et al (2004) BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099–7109. https://doi.org/10.1158/0008-5472.Can-04-1443

    CAS  Article  PubMed  Google Scholar 

  39. Yang QK, Chen T, Wang SQ, Zhang XJ, Yao ZX (2020) Apatinib as targeted therapy for advanced bone and soft tissue sarcoma: a dilemma of reversing multidrug resistance while suffering drug resistance itself. Angiogenesis 23:279–298. https://doi.org/10.1007/s10456-020-09716-y

    CAS  Article  PubMed  Google Scholar 

  40. Yao X, Corbett T, Gupta AA, Kandel RA, Verma S, Werier J, Ghert M (2014) A systematic review of active treatment options in patients with desmoid tumours. Curr Oncol 21:e613-629. https://doi.org/10.3747/co.21.1995

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported, in part, by the Chengdu Science and Technology Program Projects (2017-CY02-00032-GX), National Natural Science Foundation of China (No. 81702664 and 81801852), and National Key Research and Development Program of China (No. 2016YFC1102003 and 2017YFB0702604).

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Correspondence to Li Min.

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This retrospective study was performed using data from anonymized patients who received apatinib treatment between October 2017 and January 2020. Because of the nature of retrospective design and patient anonymization, the ethical board of Sichuan University West China Hospital approved the retrospective study.

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Written informed consent of off-label treatment was obtained from all patients before treatment.

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Zheng, C., Fang, J., Wang, Y. et al. Efficacy and safety of apatinib for patients with advanced extremity desmoid fibromatosis: a retrospective study. J Cancer Res Clin Oncol (2021). https://doi.org/10.1007/s00432-020-03498-y

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Keywords

  • Desmoid fibromatosis
  • Apatinib
  • Tyrosine kinase inhibitor
  • Efficacy
  • Safety