Postmenopausal Women who Progress on Fulvestrant ('Faslodex') Remain Sensitive to Further Endocrine Therapy
Purpose. This retrospective evaluation of data from two randomized, multicenter trials examined whether tumor responses to further endocrine therapy were seen in postmenopausal women with advanced breast cancer who had progressed on both initial endocrine therapy, usually tamoxifen, and on the estrogen receptor (ER) antagonist fulvestrant ('Faslodex').
Patients and methods. A combined total of 423 patients received fulvestrant 250 mg as a monthly intramuscular injection. After progression on fulvestrant, some patients received another endocrine therapy. Responses to subsequent endocrine therapy were assessed using a questionnaire sent to the trial investigators. Best responses were classified as a complete or partial response (CR or PR), stable disease (SD) lasting ≥24 weeks, or disease progression.
Results. Follow-up data were available for 54 patients who derived clinical benefit (CB, defined as CR, PR or SD) from fulvestrant and who received subsequent endocrine therapy, resulting in a PR in 4 patients, SD in 21 patients, and disease progression in 29 patients. Data were available for 51 patients who derived no CB from fulvestrant and who received further endocrine therapy, resulting in a PR in 1 patient, SD in 17 patients, and disease progression in 33 patients. Aromatase inhibitors were used as subsequent endocrine therapy in >80% of patients.
Conclusions. After progression on fulvestrant, patients may retain sensitivity to other endocrine agents. Fulvestrant provides an additional option to existing endocrine therapies for the treatment of advanced or metastatic breast cancer in postmenopausal women, and may provide the opportunity to extend the sequence of endocrine regimens before cytotoxic chemotherapy is required.
Unable to display preview. Download preview PDF.
- 1.Bray F, Sankila R, Ferlay J, Parkin DM: Estimates of cancer incidence and mortality in Europe in 1995. Eur J Cancer 38: 99-166, 2002Google Scholar
- 2.Nabholtz JM, Buzdar A, Pollak M, Harwin W, Burton G, Mangalik A, Steinberg M, Webster A, von Euler M: 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: 3758-3767, 2000Google Scholar
- 3.Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Janicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Lassus M, Verbeek JA, Staffler B, Chaudri-Ross HA, Dugan M: Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 19: 2596-2606, 2001Google Scholar
- 4.Buzdar AU, Hortobagyi G: Update on endocrine therapy for breast cancer. Clin Cancer Res 4: 527-534, 1998Google Scholar
- 5.Hortobagyi GN: Progress in endocrine therapy for breast carcinoma. Cancer 83: 1-6, 1998Google Scholar
- 6.Stenbygaard LE, Herrstedt J, Thomsen JF, Svendsen KR, Engelholm SA, Dombernowsky P: Toremifene and tamoxifen in advanced breast cancer-a double-blind cross-over trial. Breast Cancer Res Treat 25: 57-63, 1993Google Scholar
- 7.Wakeling AE, Dukes M, Bowler J: A potent specific pure antiestrogen with clinical potential. Cancer Res 51: 3867-3873, 1991Google Scholar
- 8.Robertson JF, Nicholson RI, Bundred NJ, Anderson E, Rayter Z, Dowsett M, Fox JN, Gee JM, Webster A, Wakeling AE, Morris C, Dixon M: Comparison of the short-term biological effects of 7alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5(10)-triene-3,17beta-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast cancer. Cancer Res 61: 6739-6746, 2001Google Scholar
- 9.Osborne CK, Jarman M, McCague R, Coronado EB, Hilsenbeck SG, Wakeling AE: The importance of tamoxifen metabolism in tamoxifen-stimulated breast tumor growth. Cancer Chemother Pharmacol 34: 89-95, 1994Google Scholar
- 10.Osborne CK, Coronado-Heinsohn EB, Hilsenbeck SG, McCue BL, Wakeling AE, McClelland RA, Manning DL, Nicholson RI: Comparison of the effects of a pure steroidal antiestrogen with those of tamoxifen in a model of human breast cancer. J Natl Cancer Inst 87: 746-750, 1995Google Scholar
- 11.Howell A, DeFriend D, Robertson J, Blamey R, Walton P: Response to a specific antiestrogen (ICI 182780) in tamoxifenresistant breast cancer. Lancet 345: 29-30, 1995Google Scholar
- 12.Howell A, DeFriend DJ, Robertson JF, Blamey RW, Anderson L, Anderson E, Sutcliffe FA, Walton P: Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer. Br J Cancer 74: 300-308, 1996Google Scholar
- 13.Howell A, Robertson JFR, Quaresma Albano J, Aschermannova A, Mauriac L, Kleeberg UR, Vergote I, Erikstein B, Webster A, Morris C: Fulvestrant, formerly ICI 182,780 is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol 20: 3396-2403, 2002Google Scholar
- 14.Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S, Gertler SZ, May JT, Burton G, Dimery I, Webster A, Morris C, Elledge R, Buzdar A: A double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol 20: 3386-3395, 2002Google Scholar
- 15.Kaufmann M, Bajetta E, Dirix LY, Fein LE, Jones SE, Cervek J, Fowst C, Polli A, di Salle E, Arkhipov A, Piscitelli G, Massimini G: Survival advantage of exemestane (EXE, Aromasin) over megestrol acetate (MA) in postmenopausal women with advanced breast cancer (ABC) refractory to tamoxifen: results of a phase III randomized double-blind study. Proc Am Soc Clin Oncol 18: 108a, 1999 (abstract 412)Google Scholar
- 16.Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, EiermannW, Wolter JM, Azab M, Webster A, Plourde PV: Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. Arimidex Study Group. J Clin Oncol 14: 2000-2011, 1996Google Scholar
- 17.Dombernowsky P, Smith I, Falkson G, Leonard R, Panasci L, Bellmunt J, Bezwoda W, Gardin G, Gudgeon A, Morgan M, Fornasiero A, Hoffmann W, Michel J, Hatschek T, Tjabbes T, Chaudri HA, Hornberger U, Trunet PF: Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol 16: 453-461, 1998Google Scholar
- 18.Howell A, Howell SJ, Clarke R, Anderson E: Where do selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) now fit into breast cancer treatment algorithms? J Steroid Biochem Mol Biol 79: 227-237, 2001Google Scholar
- 19.Robertson JFR, Howell A, Buzdar A, von Euler M, Lee D: Static disease on anastrozole provides similar benefit as objective response in patients with advanced breast cancer. Breast Cancer Res Treat 58: 157-162, 1999Google Scholar
- 20.Cheung KL, Willsher PC, Pinder SE, Ellis IO, Elston CW, Nicholson RI, Blamey RW, Robertson JF: Predictors of response to second-line endocrine therapy for breast cancer. Breast Cancer Res Treat 45: 219-224, 1997Google Scholar
- 21.Kurebayashi J, Sonoo H, Inaji H, Nishimura R, Iino Y, Toi M, Kobayashi S, Saeki T: Endocrine therapies for patients with recurrent breast cancer: predictive factors for responses to first-and second-line endocrine therapies. Oncology 59: 31-37, 2000Google Scholar
- 22.Perey L, Thürlimann B, Hawle H, Bonnefoi H, Aebi A, Pagani O, Goldhirsch A, Dietrich D: Fulvstrant ('Faslodex') as a hormonal treatment in postmenopausal patients with advanced breast cancer progressing after treatment with tamoxifen and non-steroidal aromatase inhibitors: an ongoing phase II SAKK trial. Ann Oncol 13: 172P, 2002Google Scholar