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Moving Beyond Response Criteria: New Measures of Success in the Treatment of Sarcomas

  • Sarcomas (SH Okuno, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

There is an urgent need to develop new therapies for soft tissue sarcomas. Traditional cytotoxic therapies, such as doxorubicin and ifosfamide, have been the standard approach to this disease. However, newer paradigms are emerging that are less toxic while targeting dysregulated pathways, tumor hypoxia, and genetic translocations. These newer therapies require different measures of activity as standard response criteria may inaccurately measure their effectiveness. Serious consideration of select endpoints and measures of tumor response are crucial to make significant strides in the treatment of sarcomas. Current studies on soft tissue sarcomas are slowly abandoning response rates while employing progression-free survival and time to progression as improved endpoints. With time and data, our understanding of the relative activity of these agents will grow and lead to improved benefits for our patients.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Rosenberg SA, Tepper J, Glatstein E, et al. The treatment of soft-tissue sarcomas of the extremities. Ann Surg. 1982;196(3):305–15.

    Article  PubMed  CAS  Google Scholar 

  2. Aljubrani AH, Griffin A, Pintilie M, et al. Osteosarcoma in adolescents and adults: survival analysis with and without lung metastases. Ann Oncol. 2009;20:1136–41.

    Article  Google Scholar 

  3. Grier HE, Krailo MD, Tarbell NJ, et al. Addition of ifosfamide and etoposide to standard chemotherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med. 348;8:694–701.

  4. American Cancer Society. Cancer facts and figures 2012.

  5. Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J, editors. SEER Survival monograph: cancer survival among adults: U.S. SEER Program, 1988–2001, patient and tumor characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07–6215, Bethesda, MD; 2007.

  6. Lorigan PC, Verweij J, Papai Z, et al. Randomized phase III trial of two investigational schedules of ifosfamide versus standard dose doxorubicin in patients with advanced or metastatic soft tissue sarcoma. Proc Am Soc Clin Oncol. 2002;21:353a.

    Google Scholar 

  7. Nielsen OS, Blay JY, Judson IR, et al. Metastatic soft tissue sarcoma in adults: prognosis and treatment options. Am J Cancer. 2003;2:211–21.

    Article  CAS  Google Scholar 

  8. Demetri GD, Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347.

  9. Verweig J. Soft tissue sarcoma trials: one size no longer fits all. J Clin Oncol. 2009;27:3085–7.

    Article  Google Scholar 

  10. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.

    Article  PubMed  CAS  Google Scholar 

  11. Buyse M, Thirion P, Carlson RW, et al. Relation between tumor response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis. Meta-analysis group in Cancer. Lancet. 2000;356:373–8.

    Article  PubMed  CAS  Google Scholar 

  12. Goffin J, Baral S, Tu D, et al. Objective responses in patients with malignant melanoma or renal cell cancer in early clinical studies do not predict regulatory approval. Clin Cancer Res. 2005;15:5928–34.

    Article  Google Scholar 

  13. El-Maraghi RH, Eisenhauer EA. Review of phase II trial designs used in studies of molecular targeted agents: outcomes and predictors of success in phase III. J Clin Oncol. 2008;10:1346–54.

    Article  Google Scholar 

  14. Benz MR, Czernin J, Allen-Auerbach MS, et al. FDG-PET/CT imaging predicts histopathologic treatment responses after the initial cycle of neoadjuvant chemotherapy in high-grade soft-tissue sarcomas. Clin Cancer Res. 2009;15:2856–63.

    Article  PubMed  CAS  Google Scholar 

  15. Ross PJ, McKenna S, A'Hern R, et al. Improved survival following pulmonary metastasectomy in soft tissue sarcoma (STS): comparison of cohorts treated with and without resection. Proc Am Soc Clin Oncol. 2003;22 (abstract 3304).

  16. Van Glabbeke M, van Oosterom AT, Oosterhuis JW, et al. Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens. A European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group study. J Clin Oncol. 1999;17:150–7.

    PubMed  Google Scholar 

  17. Verweij J. Soft tissue sarcoma trials: one size no longer fits all. J Clin Oncol. 2008;27:3085–7.

    Article  Google Scholar 

  18. Blanke CD, Demetri GD, von Mehren M, et al. 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. 2008;26:620–5.

    Article  PubMed  CAS  Google Scholar 

  19. Choi H, Charnsangavej C, de Castro Faria S, et al. CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: a quantitative analysis correlated with FDG PET findings. AJR Am J Roentgenol. 2004;183:1619–28.

    PubMed  Google Scholar 

  20. Benjamin B, Choi H, Macapinlac A. We should desist using RECIST, at least in GIST. J Clin Oncol. 2007;25:1760–4.

    Article  PubMed  Google Scholar 

  21. LeCesne A, Van Glabbeke M, Verweij J, et al. Absence of progression as assessed by response evaluation criteria in solid tumors predicts survival in advanced GI stromal tumors treated with imatinib mesylate: the Intergroup EORTC-ISG-AGITG Phase III Trial. J Clin Oncol. 2009;27:3969–74.

    Article  CAS  Google Scholar 

  22. Fayette J, Coquard IR, Alberti L, Ranchere D, Boyle H, Blay JY. ET-743: a novel agent with activity in soft tissue sarcomas. Oncologist. 2005;10:827–32.

    Article  PubMed  CAS  Google Scholar 

  23. Yovine A, Riofrio M, Blay JY, et al. Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients. J Clin Oncol. 2004;22:890–9.

    Article  PubMed  CAS  Google Scholar 

  24. Le Cesne A, Blay JY, Judson I, et al. Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. J Clin Oncol. 2005;23:576–84.

    Article  PubMed  Google Scholar 

  25. Garcia-Carbonero R, Supko JG, et al. Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study. J Clin Oncol. 2005;23:5484–92.

    Article  PubMed  CAS  Google Scholar 

  26. Demetri GD, Chawla SP, von Mehren M, et al. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009;27:4188–96.

    Article  PubMed  CAS  Google Scholar 

  27. Van Der Graaf WT, Blay J, Chawla SP, et al. PALETTE: a randomized, double-blind, phase III trial of pazopanib versus placebo in patients (pts) with soft-tissue sarcoma (STS) whose disease has progressed during or following prior chemotherapy—An EORTC STBSG Global Network Study (EORTC 62072). J Clin Oncol. 2011;29 Suppl (abstract LBA10002). This is the culmination of newer approaches in sarcoma endpoints. In this study, progression-free survival was the primary endpoint and liposarcomas were excluded. This may lead to a new drug approval for soft tissue sarcoma.

  28. Mita MM, Britten CD, Poplin E, et al. Deforolimus Trial 106: A Phase I trial evaluating 7 regimens of oral Deforolimus (AP23573, MK-8669). J Clin Oncol. 2008;26:3509. meeting abstracts.

    Article  Google Scholar 

  29. Chawla SP, Staddon AP, Baker, et al. Phase II study of the mammalian target of rapamycin inhibitor ridaforolimus in patients with advanced bone and soft tissue sarcomas. J Clin Oncol. 2012;30(1):78–84.

    Article  PubMed  CAS  Google Scholar 

  30. Chawla SP, Blay J, Ray-Coquard IL, et al. Results of the phase III, placebo-controlled trial (SUCCEED) evaluating the mTOR inhibitor ridaforolimus as maintenance therapy in advanced sarcoma patients following clinical benefit from prior standard cytotoxic chemotherapy. J Clin Oncol. 2011;29 Suppl (abstract 10005). This study is the first phase 3 evaluation of a maintenance therapy in sarcomas. Another study utilizing progression-free survival as an endpoint after demonstration of response or disease stability.

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Authors and Affiliations

  1. Sarcoma Oncology Center, 2811 Wilshire Blvd. Suite 414, Santa Monica, CA, 90403, USA

    Andrew E. Hendifar MD, MPH & Sant P. Chawla MD

  2. Division of Orthopedic Oncology, Department of Orthopedic Surgery, Keck School of Medicine, Los Angeles County Medical Center, University of Southern California, 1520 San Pablo Street, Suite 2000, Los Angeles, CA, 90033, USA

    Elke Ahlmann MD, Daniel C. Allison MD, James Hu MD & Lawrence Menendez MD

Authors
  1. Andrew E. Hendifar MD, MPH
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  2. Elke Ahlmann MD
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  3. Daniel C. Allison MD
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  4. James Hu MD
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  5. Lawrence Menendez MD
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  6. Sant P. Chawla MD
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Corresponding author

Correspondence to Andrew E. Hendifar MD, MPH.

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Hendifar, A.E., Ahlmann, E., Allison, D.C. et al. Moving Beyond Response Criteria: New Measures of Success in the Treatment of Sarcomas. Curr. Treat. Options in Oncol. 13, 299–305 (2012). https://doi.org/10.1007/s11864-012-0197-1

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  • DOI: https://doi.org/10.1007/s11864-012-0197-1

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