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Efficacy of Exemestane After Nonsteroidal Aromatase inhibitor Use in Metastatic Breast Cancer Patients

  • Kim, Sun-Hye (Center for Clinical Trials, National Cancer Center) ;
  • Park, In-Hae (Center for Clinical Trials, National Cancer Center) ;
  • Lee, Hye-Won (Center for Clinical Trials, National Cancer Center) ;
  • Lee, Keun-Seok (Center for Breast Cancer, National Cancer Center) ;
  • Nam, Byung-Ho (Center for Clinical Trials, National Cancer Center) ;
  • Ro, Jung-Sil (Center for Clinical Trials, National Cancer Center)
  • Published : 2012.03.31

Abstract

Background : Previous studies have suggested a lack of complete cross-resistance between steroidal (exemestane) and non-steroidal aromatase inhibitors (nSAI). Methods : Eighty-eight metastatic breast cancer (MBC) patients who received 25 mg of exemestane orally once a day at the National Cancer Center, Korea, between 2003 and 2009, were reviewed retrospectively. All patients had received nSAI for metastatic disease prior to exemestane therapy. Results : The median age was 52 years (range, 33-79), and 13 (14.8%) patients were premenopausal who concomitantly received GnRH agonist. Exemestane was given as a second- (80.7%) or third-line (19.3%) hormone therapy. The clinical benefit (CB) rate (complete response + partial response + stable disease ${\geq}$ 24 weeks) was 30.7%, with a median CB duration of 10.0 months (range, 6.3-78.7). The median progression-free survival (PFS) was 3.0 months (95% confidence interval [CI], 1.99-4.01) and the overall survival (OS) 21.5 months (95% CI, 17.96-25.04), with a median followup of 50.3 months. Patients who achieved CB had longer OS than those patients who did not (29.6 vs 17.9 months; P=0.002). On univariate analysis of predictive factors, patients who had achieved CB from previous nSAI tended to show lower CB rate (24.6% vs 44.4%, respectively; P=0.063) and shorter PFS (2.8 vs 4.8 months, respectively; p=0.233) than patients who had not. Achieving CB from previous nSAI became independent predictive factor for CBR to exemestane on multivariable analysis (Odds ratio = 2.852, P = 0.040). Conclusions : Exemestane after nSAI failure was effective in prolonging CB duration. The drug's efficacy seemed to be inferior in patients who had benefit from previous nSAI use.

References

  1. BBertelli G, Garrone O, Merlano M, et al (2005). Sequential treatment with exemestane and non-steroidal aromatase inhibitors in advanced breast cancer. Oncology, 69, 471-7. https://doi.org/10.1159/000090985
  2. Bonneterre J, Thurlimann B, Robertson J F, et al (2000). Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. J Clin Oncol, 18, 3748- 57. https://doi.org/10.1200/JCO.2000.18.22.3748
  3. Chia S, Gradishar W, Mauriac L, et al (2008). Doubleblind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol, 26, 1664-70. https://doi.org/10.1200/JCO.2007.13.5822
  4. Chin Y S, Beresford M J, Ravichandran D, et al (2007). Exemestane after non-steroidal aromatase inhibitors for post-menopausal women with advanced breast cancer. Breast, 16, 436-9. https://doi.org/10.1016/j.breast.2007.02.002
  5. Gennatas C, Michalaki V, Carvounis E, et al (2006). Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on letrozole or anastrozole. A phase II trial conducted by the Hellenic Group of Oncology (HELGO). Tumori, 92, 13-7.
  6. Kurebayashi J, Sonoo H, Inaji H, et al (2000). Endocrine therapies for patients with recurrent breast cancer: predictive factors for responses to first- and second-line endocrine therapies. Oncology, 59, Suppl 1, 31-7.
  7. Lonning P E (2009). Lack of complete cross-resistance between different aromatase inhibitors; a real finding in search for an explanation? Eur J Cancer, 45, 527-535. https://doi.org/10.1016/j.ejca.2008.10.019
  8. Lonning P E, Bajetta E, Murray R, et al (2000). Activity of exemestane in metastatic breast cancer after failure of nonsteroidal aromatase inhibitors: a phase II trial. J Clin Oncol, 18, 2234-44. https://doi.org/10.1200/JCO.2000.18.11.2234
  9. Macedo L F, Guo Z, Tilghman S L, et al (2006). Role of androgens on MCF-7 breast cancer cell growth and on the inhibitory effect of letrozole. Cancer Res, 66, 7775-82. https://doi.org/10.1158/0008-5472.CAN-05-3984
  10. McShane L M, Altman D G, Sauerbrei W, et al (2005). Reporting recommendations for tumor marker prognostic studies. J Clin Oncol, 23, 9067-72. https://doi.org/10.1200/JCO.2004.01.0454
  11. Miller W R, Anderson T J, Evans D B, et al (2003). An integrated view of aromatase and its inhibition. J Steroid Biochem Mol Biol, 86, 413-421. https://doi.org/10.1016/S0960-0760(03)00352-2
  12. Miller W R, Bartlett J, Brodie A M, et al (2008). Aromatase inhibitors: are there differences between steroidal and nonsteroidal aromatase inhibitors and do they matter? Oncologist, 13, 829-37. https://doi.org/10.1634/theoncologist.2008-0055
  13. Mouridsen H, Gershanovich M, Sun Y, et al (2003). Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol, 21, 2101-9. https://doi.org/10.1200/JCO.2003.04.194
  14. Muss H B (1992). Endocrine therapy for advanced breast cancer: a review. Breast Cancer Res Treat, 21, 15-26. https://doi.org/10.1007/BF01811960
  15. Nabholtz J M, Buzdar A, Pollak M, et al (2000). Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. J Clin Oncol, 18, 3758-67. https://doi.org/10.1200/JCO.2000.18.22.3758
  16. Nam B H, Kim S Y, Han H S, et al (2008). Breast cancer subtypes and survival in patients with brain metastases. Breast Cancer Res, 10, R20. https://doi.org/10.1186/bcr1870
  17. Paridaens R J, Dirix L Y, Beex L V, et al (2008). Phase III study comparing exemestane with tamoxifen as firstline hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. J Clin Oncol, 26, 4883-90. https://doi.org/10.1200/JCO.2007.14.4659
  18. Santen R J, Manni A, Harvey H, et al (1990). Endocrine treatment of breast cancer in women. Endocr Rev, 11, 221-65. https://doi.org/10.1210/edrv-11-2-221
  19. Smith I E, Dowsett M (2003). Aromatase inhibitors in breast cancer. N Engl J Med, 348, 2431-42. https://doi.org/10.1056/NEJMra023246
  20. Steele N, Zekri J, Coleman R, et al (2006). Exemestane in metastatic breast cancer: effective therapy after thirdgeneration non-steroidal aromatase inhibitor failure. Breast, 15, 430-6.
  21. Suzuki T, Miki Y, Moriya T, et al (2007). 5Alpha-reductase type 1 and aromatase in breast carcinoma as regulators of in situ androgen production. Int J Cancer, 120, 285-91. https://doi.org/10.1002/ijc.22317
  22. Therasse P, Arbuck S G, Eisenhauer E A, et al (2000). 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, 92, 205-16. https://doi.org/10.1093/jnci/92.3.205

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