Skip to main content

Advertisement

SpringerLink
Log in

Long-term efficacy of imatinib for treatment of metastatic GIST

  • Review Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Imatinib is an effective and approved treatment for advanced gastrointestinal stromal tumor (GIST). Continuous imatinib treatment is recommended by current guidelines. This review summarizes the long-term efficacy and safety of imatinib for patients with metastatic GIST.

Methods

Key clinical studies were reviewed—including B2222, S0033, and BFR14—with particular emphasis on recently reported results of the long-term clinical outcome of imatinib for metastatic GIST.

Results

The B2222 and S0033 studies recently reported 10-year follow-up results that demonstrate the long-term efficacy of imatinib. Furthermore, results from the BFR14 study demonstrate that imatinib treatment should not be interrupted and that the efficacy of imatinib following reintroduction is inferior compared with the continuous administration group. The S0033 study also supports the importance of dose optimization and dose escalation of imatinib in patients with KIT exon 9 mutations or progressive disease. These studies demonstrate that individual patient characteristics should be evaluated for optimal patient management. Managing adverse events proactively is very important to maintain compliance.

Conclusions

The results from these studies demonstrate that long-term imatinib extends survival in patients with advanced GIST. Furthermore, these studies support the safety of long-term imatinib therapy in this patient population.

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

Similar content being viewed by others

References

  1. Demetri GD, Benjamin RS, Blanke CD et al (2007) NCCN task force report: management of patients with gastrointestinal stromal tumor (GIST)—update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw 5(Suppl 2):S1–S29

    PubMed  Google Scholar 

  2. Ducimetiere F, Lurkin A, Ranchere-Vince D et al (2011) Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing. PLoS One 6:Abstract e20294

  3. Perez EA, Livingstone AS, Franceschi D et al (2006) Current incidence and outcomes of gastrointestinal mesenchymal tumors including gastrointestinal stromal tumors. J Am Coll Surg 202:623–629

    Article  PubMed  Google Scholar 

  4. Nilsson B, Bumming P, Meis-Kindblom JM et al (2005) Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era—a population-based study in western Sweden. Cancer 103:821–829

    Article  PubMed  Google Scholar 

  5. Miettinen M, Sarlomo-Rikala M, Lasota J (1999) Gastrointestinal stromal tumors: recent advances in understanding of their biology. Hum Pathol 30:1213–1220

    Article  PubMed  CAS  Google Scholar 

  6. Joensuu H, Fletcher C, Dimitrijevic S et al (2002) Management of malignant gastrointestinal stromal tumours. Lancet Oncol 3:655–664

    Article  PubMed  CAS  Google Scholar 

  7. Corless CL, Heinrich MC (2008) Molecular pathobiology of gastrointestinal stromal sarcomas. Annu Rev Pathol 3:557–586

    Article  PubMed  CAS  Google Scholar 

  8. Medeiros F, Corless CL, Duensing A et al (2004) KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol 28:889–894

    Article  PubMed  Google Scholar 

  9. Heinrich MC, Corless CL, Duensing A et al (2003) PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299:708–710

    Article  PubMed  CAS  Google Scholar 

  10. Trent JC, Benjamin RS (2006) New developments in gastrointestinal stromal tumor. Curr Opin Oncol 18:386–395

    Article  PubMed  Google Scholar 

  11. Corless CL, Fletcher JA, Heinrich MC (2004) Biology of gastrointestinal stromal tumors. J Clin Oncol 22:3813–3825

    Article  PubMed  CAS  Google Scholar 

  12. Tornillo L, Terracciano LM (2006) An update on molecular genetics of gastrointestinal stromal tumours. J Clin Pathol 59:557–563

    Article  PubMed  CAS  Google Scholar 

  13. Day E, Waters B, Spiegel K et al (2008) Inhibition of collagen-induced discoidin domain receptor 1 and 2 activation by imatinib, nilotinib and dasatinib. Eur J Pharmacol 599:44–53

    Article  PubMed  CAS  Google Scholar 

  14. Savage DG, Antman KH (2002) Imatinib mesylate—a new oral targeted therapy. N Engl J Med 346:683–693

    Article  PubMed  CAS  Google Scholar 

  15. Novartis Pharmaceuticals Corporation (2009) Gleevec/Glivec prescribing information. http://www.pharma.us.novartis.com/product/pi/pdf/gleevec_tabs.pdf. Accessed 30 Jan 2013

  16. Joensuu H, Roberts PJ, Sarlomo-Rikala M et al (2001) Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344:1052–1056

    Article  PubMed  CAS  Google Scholar 

  17. Rossi S, Miceli R, Messerini L et al (2011) Natural history of imatinib-naive GISTs: a retrospective analysis of 929 cases with long-term follow-up and development of a survival nomogram based on mitotic index and size as continuous variables. Am J Surg Pathol 35:1646–1656

    Article  PubMed  Google Scholar 

  18. Casali PG, Blay JY (2010) Gastrointestinal stromal tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 21(Suppl 5):v98–v102

    Article  PubMed  Google Scholar 

  19. Demetri GD, von Mehren M, Antonescu CR et al (2010) NCCN task force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw 8(suppl 2):S1–S41

    PubMed  CAS  Google Scholar 

  20. Demetri GD, von Mehren M, Blanke CD et al (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347:472–480

    Article  PubMed  CAS  Google Scholar 

  21. Green S, Weiss GR (1992) Southwest oncology group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs 10:239–253

    Article  PubMed  CAS  Google Scholar 

  22. Blanke CD, Demetri GD, von Mehren M et al (2008) Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol 26:620–625

    Article  PubMed  CAS  Google Scholar 

  23. von Mehren M, Heinrich MC, Joensuu H et al (2011) Follow-up results after 9 years (yrs) of the ongoing, phase II B2222 trial of imatinib mesylate (IM) in patients (pts) with metastatic or unresectable KIT+ gastrointestinal tumors (GIST). J Clin Oncol 29:Abstract 10016

  24. Blanke CD, Rankin C, Demetri GD et al (2008) Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol 26:626–632

    Article  PubMed  CAS  Google Scholar 

  25. Blanke CD, Rankin C, Benjamin R et al (2011) Long-term survival on S0033—a phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumours (GISTs). Eur J Cancer 47(suppl 1):Abstract 9404

  26. Blay JY, Le Cesne A, Ray-Coquard I et al (2007) Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol 25:1107–1113

    Article  PubMed  CAS  Google Scholar 

  27. Le Cesne A, Ray-Coquard I, Bui BN et al (2010) Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol 11:942–949

    Article  PubMed  Google Scholar 

  28. Ray-Coquard IL, Bin Bui N, Adenis A et al (2010) Risk of relapse with imatinib (IM) discontinuation at 5 years in advanced GIST patients: results of the prospective BFR14 randomized phase III study comparing interruption versus continuation of IM at 5 years of treatment: a French Sarcoma Group Study. J Clin Oncol (Meeting Abstracts) 28:Abstract 10032

  29. Bertucci F, Ray-Coquard I, Bui Nguyen B et al (2012) Effect of five years of imatinib on cure for patients with advanced GIST: updated survival results from the prospective randomized Phase III BFR14 trial. J Clin Oncol 30:Abstract 10095

  30. Domont J, Blay J, Ray-Coquard IL et al (2011) Influence of imatinib interruption and imatinib rechallenge on the residual tumor volume in patients with advanced GIST: Result of the BFR14 prospective French Sarcoma Group randomized phase III trial. J Clin Oncol 29:Abstract 10054

  31. Perol D, Ray-Coquard I, Bui Nguyen B et al (2012) Explored prognostic factors for survival in patients with advanced GIST treated with standard dose imatinib (IM): results from the BFR14 phase III trial of the French Sarcoma Group. J Clin Oncol 30:Abstract 10092

  32. Zalcberg JR, Verweij J, Casali PG et al (2005) Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg. Eur J Cancer 41:1751–1757

    Article  PubMed  CAS  Google Scholar 

  33. Demetri GD, Wang Y, Wehrle E et al (2009) Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors. J Clin Oncol 27:3141–3147

    Article  PubMed  CAS  Google Scholar 

  34. Yoo C, Ryu MH, Kang BW et al (2010) Cross-sectional study of imatinib plasma trough levels in patients with advanced gastrointestinal stromal tumors: impact of gastrointestinal resection on exposure to imatinib. J Clin Oncol 28:1554–1559

    Article  PubMed  CAS  Google Scholar 

  35. Heinrich MC, Corless CL, Demetri GD et al (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21:4342–4349

    Article  PubMed  CAS  Google Scholar 

  36. Debiec-Rychter M, Dumez H, Judson I et al (2004) Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 40:689–695

    Article  PubMed  CAS  Google Scholar 

  37. Blesius A, Cassier PA, Ray-Coquard IL et al (2011) Who are the long responders to imatinib (IM) in patients with advanced GIST? Results of the BFR14 prospective French Sarcoma Group randomized phase III trial. J Clin Oncol 29:Abstract 10048

  38. Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST) (2010) Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. J Clin Oncol 28:1247–1253

    Google Scholar 

  39. Joensuu H, Trent JC, Reichardt P (2011) Practical management of tyrosine kinase inhibitor-associated side effects in GIST. Cancer Treat Rev 37:75–88

    Article  PubMed  CAS  Google Scholar 

  40. Le Cesne A, Ray-Coquard IL, Bui Nguyen B et al (2011) Time to secondary resistance (TSR) after interruption of imatinib (IM) in advanced GIST: updated results of the prospective French Sarcoma Group randomized phase III trial on long-term survival. J Clin Oncol 29:Abstract 10015

  41. Halpern R, Barghout V, Zarotsky V, Williams DE (2009) Costs and utilization associated with imatinib adherence in patients with chronic myeloid leukemia or gastrointestinal stromal tumors. J Clin Outcomes Manag 16:215–223

    Google Scholar 

  42. Noens L, Van Lierde MA, De Bock R et al (2009) Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood 113:5401–5411

    Article  PubMed  CAS  Google Scholar 

  43. Mazzeo F, Duck L, Joosens E et al (2011) Nonadherence to imatinib treatment in patients with gastrointestinal stromal tumors: the ADAGIO study. Anticancer Res 31:1407–1409

    PubMed  Google Scholar 

Download references

Acknowledgments

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. I thank Anju Roy, Ph.D., for her medical editorial assistance with this manuscript. This work was supported by Novartis Pharmaceuticals.

Conflict of interest

  Consultant/Advisor: Novartis Pharmaceuticals, Johnson and Johnson, Merck, GlaxoSmithKline, Morphotek; Research Grants: Johnson and Johnson, PharmaMar, Eisai, Infinity.

Author information

Authors and Affiliations

  1. Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Shreyaskumar Patel

Authors
  1. Shreyaskumar Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shreyaskumar Patel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Patel, S. Long-term efficacy of imatinib for treatment of metastatic GIST. Cancer Chemother Pharmacol 72, 277–286 (2013). https://doi.org/10.1007/s00280-013-2135-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-013-2135-8

Keywords

Search

Navigation