Switching treatment to exemestane after 2–3 years on tamoxifen, improves disease-free survival* and seems to modestly reduce risk of death, according to an Online/Article published today (Tuesday February 13) by The Lancet.
The Intergroup Exemestane Study (IES), an extensive, international study, tested the superiority of switching to exemestane (an aromatase inhibitor**) from tamoxifen in patients with early breast cancer. Switching treatment was expected to improve disease-free survival and decrease the side-effects of prolonged treatment by limiting exposure to both drugs. Early release on the results of IES*** was prompted by a significant early improvement in disease-free survival.
In a new analysis of the IES trial, with a median follow-up of almost 5 years, and more than 10 000 women-years of post-treatment information, Charles Coombes (Imperial College London, London, UK) and colleagues at The Institute of Cancer Research, investigated whether early disease-related benefits persisted after treatment, and whether any long-term adverse risks have emerged. The new analysis confirms the favourable effect of switching on the risk of relapse. The analysis also suggests a modest improvement in overall survival after excluding the patients subsequently found to be oestrogen-receptor-negative.
The authors conclude: "The findings of IES show that the benefit of sequential administration of tamoxifen and an aromatase inhibitor in patients with endocrine-responsive breast cancer persists for some years after discontinuation of the aromatase inhibitor. …future research should investigate whether molecular markers exist that predict which patients benefit from endocrine treatment strategy. "
In an accompanying Comment, Francesco Boccardo and Alessandra Rubagotti (National Cancer Institute and University of Genoa Medical School, Genoa, Italy) state: "These findings provide some limited evidence to advise all women being administered tamoxifen to switch, even though this approach is not devoid of potentially serious side-effects…[whose] incidence was low and the available data do not indicate any increase in the risk of death unrelated to breast cancer in the women switched to aromatase inhibitors."
Laura Gallagher, Press Office, Imperial College, UK. T)+44 (0)207 594 6702 or mobile (out of hours) 0780 388 6248 L.Gallagher@imperial.ac.uk
Comment Dr Francesco Boccardo, National Cancer Institute, Genoa, Italy. T)+39 010 5600 560/503 (secretary) f.boccardo@unige.it
Notes to Editors
* Disease-free survival—survival free of local and distant breast cancer recurrence, new primary breast cancer, and death without disease relapse.
** Large randomised trials have reported early improvements in disease-free survival during treatment with an aromatase inhibitor compared with tamoxifen in the adjuvant setting. This benefit is accompanied by a reduction in the commonly recognised side-effects of tamoxifen. However, concern has been raised about the effects of aromatase inhibitors on bone loss and the cardiovascular system.
** *At the time of publication more than 90% of patients had completed allocated treatment. With a median follow-up of 30.6 months, 449 disease-free survival events, and 199 deaths, switching to exemestane reduced the risk of events contributing to the analysis of disease-free survival by 32%, but at this early time point, overall survival did not differ between the treatment groups.
Journal
The Lancet