Spreading the word, but not too thinly
Authors: Anthony Howell, C Kent Osborne, Louis Mauriac
Journal: The Lancet (2004)

We are writing in response to the Commentary by Nicholas Wilcken and Martin Stockler (Oct 18, p 1254).1Wilcken NRC Stockler MR Fulvestrant: spreading the word, but not too thinly.Lancet. 2003; 362: 1254Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar As principal investigators in the two randomised trials of fulvestrant versus anastrozole,2Howell A Robertson JFR Albano JQ et al.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. 2002; 20: 3396-3403Crossref PubMed Scopus (591) Google Scholar, 3Osbourne CK Pippen J Jones SE et al.Double-blind, randomised 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. 2002; 20: 3386-3395Crossref PubMed Scopus (572) Google Scholar and lead author of the paper cited in the Commentary,4Mauriac L Pippen JE Quaresma Albano J Gertler SZ Osborne CK Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials.Eur J Cancer. 2003; 39: 1228-1233Summary Full Text Full Text PDF PubMed Scopus (75) Google Scholar we feel justified in responding to the comments made. The primary publications from the two phase III randomised trials of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer (trial 020, in Europe, South Africa, and Australia; trial 021 in North America) were published together in the Journal of Clinical Oncology in 2002.2Howell A Robertson JFR Albano JQ et al.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. 2002; 20: 3396-3403Crossref PubMed Scopus (591) Google Scholar, 3Osbourne CK Pippen J Jones SE et al.Double-blind, randomised 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. 2002; 20: 3386-3395Crossref PubMed Scopus (572) Google Scholar The Commentary by Wilcken and Stockler uses the recently published paper by Mauriac and colleagues4Mauriac L Pippen JE Quaresma Albano J Gertler SZ Osborne CK Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials.Eur J Cancer. 2003; 39: 1228-1233Summary Full Text Full Text PDF PubMed Scopus (75) Google Scholar as an example of multiple reporting of clinical trial data and the questionable value of subanalyses. The paper by Mauriac and colleagues reports a subgroup analysis of combined data from both phase III trials; examination of response by site of metastases was not included in the primary papers and therefore does not constitute multiple reporting. Although caution is rightly required when interpreting results of retrospective subgroup analyses, results from these tests can nevertheless be informative and useful in shaping future trials. In this case, patients with advanced breast cancer and visceral metastases are often believed not to respond to endocrine therapy as well as those with non-visceral metastases, and are therefore preferentially treated with cytotoxic chemotherapy. We believe that an examination of the efficacy of two different types of endocrine therapy in this subgroup of patients using a database generated from two large clinical trials addresses a clinically important question. We made no attempt to “confuse the knowledge base”, because the origin of the patients used in the subgroup analysis was clearly explained and attributed to trials 020 and 021, and the primary publications were fully referenced in Mauriac and colleagues' article. In response to Wilcken and Stockler's statement on the statistical frailty of subgroup analyses, we would like to note that no statistical claims were presented for any comparisons made in this paper; p values were included for completeness only. Finally, Wilcken and Stockler make reference to the absence of overall survival data in the three publications referenced. At the time these papers were submitted for publication, survival data from the two trials were immature and therefore not available for inclusion. These data are now available and will be in the public domain by the end of 2003. The authors are advisory board members and members of speaker's bureaux for AstraZeneca.