Comparing duration of response and duration of clinical benefit between fulvestrant treatment groups in the CONFIRM trial: application of new methodology.
duration of response; duration of clinical benefit; methodology; comparison; advanced breast cancer; Fulvestrant; oncology
Abstract :
[en] Comparisons of duration of response (DoR) and duration of clinical benefit (DoCB) within clinical trials are prone to biases. To address these biases, we used new methodology to prospectively analyze expected DoR and expected DoCB. Objective response rate and clinical benefit rate were calculated for fulvestrant 500 and 250 mg, and used to calculate expected DoR and expected DoCB for each dose group. The ratios for expected DoR and expected DoCB (expected DoR500/expected DoR250 and expected DoCB500/expected DoCB250) were then calculated, thereby allowing statistical comparisons of these endpoints between each arm of the COmparisoN of Faslodex In Recurrent or Metastatic breast cancer (CONFIRM) trial. Expected DoRs for fulvestrant 500 and 250 mg were 3.2 and 3.6 months, respectively. The expected DoR ratio between fulvestrant 500 and 250 mg was not statistically significant (0.89; 95 % CI, 0.48-1.67, P = 0.724). The expected DoCBs for fulvestrant 500 and 250 mg were 9.8 and 7.2 months, respectively. The expected DoCB ratio showed that the expected DoCB for fulvestrant 500 mg was significantly improved compared with the expected DoCB for fulvestrant 250 mg (1.36; 95 % CI, 1.07-1.73, P = 0.013). Analysis of the expected DoR and expected DoCB showed fulvestrant 500 mg significantly increased expected DoCB compared with fulvestrant 250 mg in the CONFIRM trial.
Disciplines :
Oncology
Author, co-author :
Garnett, Sally Anne
Martin, Miguel
JERUSALEM, Guy ; Centre Hospitalier Universitaire de Liège - CHU > Oncologie médicale
Comparing duration of response and duration of clinical benefit between fulvestrant treatment groups in the CONFIRM trial: application of new methodology.
Howell A, Osborne CK, Morris C, Wakeling AE (2000) ICI 182,780 (Faslodex): development of a novel, "pure" antiestrogen. Cancer 89:817-825
Robertson JF, Nicholson RI, Bundred NJ, Anderson E, Rayter Z, Dowsett M, Fox JN, Gee JM, Webster A, Wakeling AE, Morris C, Dixon M (2001) 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
DeFriend DJ, Howell A, Nicholson RI, Anderson E, Dowsett M, Mansel RE, Blamey RW, Bundred NJ, Robertson JF, Saunders C, Baum H, Walton P, Sutcliffe FA, Wakeling AE (1994) Investigation of a new pure antiestrogen (ICI 182780) in women with primary breast cancer. Cancer Res 54:408-414
Kuter I, Hegg R, Singer CF, Badwe R, Lowe E, on behalf of the NEWEST investigators (2008) Fulvestrant 500 versus 250 mg: first results from NEWEST, a randomized, phase II neoadjuvant trial in postmenopausal women with locally advanced, estrogen receptor-positive breast cancer. Breast Cancer Res Treat 109:589
Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, Verhoeven D, Pedrini JL, Smirnova I, Lichinitser MR, Pendergrass K, Garnett S, Lindemann JP, Sapunar F, Martin M (2010) Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol 28:4594-4600
European Medicines Agency (2009) Faslodex: EPAR summary for the public. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Summary-for-the- public/human/000540/WC500021169.pdf. Accessed 23 July 2011
Verma S, McLeod D, Batist G, Robidoux A, Martins IR, Mackey JR (2011) In the end what matters most? a review of clinical endpoints in advanced breast cancer. Oncologist 16:25-35
Driscoll JJ, Rixe O (2009) Overall survival: still the gold standard: why overall survival remains the definitive end point in cancer clinical trials. Cancer J 15:401-405
Zhuang SH, Xiu L, Elsayed YA (2009) Overall survival: a gold standard in search of a surrogate: the value of progression-free survival and time to progression as end points of drug efficacy. Cancer J 15:395-400
Hurvitz SA (2011) Evolving options for the treatment of metastatic breast cancer: progression-free survival as an endpoint. Cancer Treat Rev 37(7):495-504
Food and Drug Administration (2003) Oncologic drugs advisory committee meeting proceedings. 12-13 March 2003. http://www.fda.gov/ohrms/dockets/ac/ cder03.html#OncologicDrugs. Accessed 12 Sept 2011
European Medicines Agency (Committee for Medicinal Products for Human Use) (2005) Guideline on the evaluation of anticancer medicinal products in man. http://www.ema.europa.eu/docs/en-GB/document-library/Scientific-guideline/2009/ 12/WC500017748.pdf. Accessed 12 Sept 2011
European Medicines Agency (Committee for proprietary medicinal products) (2003) Points to consider on adjustment for baseline covariates. http://www.ema.europa.eu/docs/en-GB/document-library/Scientific-guideline/2009/ 09/WC500003639.pdf. Accessed 12 Sept 2011
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (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 92:205-216
Ellis S, Carroll KJ, Pemberton K (2008) Analysis of duration of response in oncology trials. Contemp Clin Trials 29:456-465
Begg CB, Larson M (1982) A study of the use of the probability-of-being- in-response function as a summary of tumor response data. Biometrics 38:59-66
Temkin NR (1978) An analysis for transient states with application to tumor shrinkage. Biometrics 34:571-580
