An analysis of two two ongoing phase III trials, TEXT and SOFT, supported in part by Pfizer, Ipsen, the International Breast Cancer Study Group, and the NCI/NIH, demonstrated that the aromatase inhibitor exemestane more effectively prevents breast cancer recurrences than tamoxifen, when given with ovarian function suppression (OFS), in premenopausal women with hormone-sensitive cancers.[1][2][3][4]
In the study, exemestane (Aromasin?; Pfizer, New York, NY 10017, USA) plus OFS reduced the relative risk of women developing a subsequent invasive cancer by 28%, and specifically reduced the relative risk of breast cancer recurrence by 34%, compared with tamoxifen (Nolvadex?; AstraZeneca, London W2 6BD, UK/Soltamox?; DARA BioSciences, Raleigh, NC 27615, USA) plus OFS.
Standard hormone therapy
?For years, tamoxifen has been the standard hormone therapy for preventing breast cancer recurrences in young women with hormone-sensitive disease. These results confirm that exemestane with ovarian function suppression constitutes a valid alternative,? said lead study author Olivia Pagani, MD, clinical director of the Breast Unit at the Oncology Institute of Southern Switzerland (IOSI) in Bellinzona, Switzerland. ?Our findings indicate that exemestane is better than tamoxifen, when given with ovarian function suppression, but longer follow up of these young women will be important to assess survival, and any long-term side effects and fertility.?
… new findings indicate that exemestane is better than tamoxifen, when given with ovarian function suppression…in premenopausal women with hormone-sensitive cancers
The TEXT and SOFT trials were led by the International Breast Cancer Study Group (IBCSG) in collaboration with the Breast International Group (BIG) and the North American Breast Cancer Group (NABCG) as a successful, worldwide collaboration spanning 27 countries and six continents. The trials were partially funded by the U.S. National Cancer Institute.
The joint analysis of TEXT and SOFT is the largest study worldwide evaluating adjuvant aromatase inhibitor therapy with OFS in young women with breast cancer, and the first to demonstrate the value of such therapy in women with hormone receptor-positive cancer. Aromatase inhibitors have primarily been used in postmenopausal women, because their use requires that women have a low level of estrogen. In the TEXT and SOFT trials, ovarian function suppression was used in premenopausal women to emulate the low estrogen levels that naturally occur in menopause.
High Risk patients
The standard adjuvant endocrine (hormone) therapy for premenopausal women is currently five years of tamoxifen. In some countries, physicians recommend adding OFS to tamoxifen in high-risk younger women. This approach is less common in the United States as the benefit of adding OFS to tamoxifen is uncertain. The SOFT trial also addresses the impact of adding OFS to tamoxifen, and the results will be available in late 2014. The joint analysis of the TEXT and SOFT trials studied the outcomes of 4,690 women, whose average age was 43 years, who were randomized to receive exemestane plus OFS or tamoxifen plus OFS for five years. OFS was achieved through treatment with the drug triptorelin, surgical oophorectomy, or ovarian irradiation. Some women also received adjuvant chemotherapy, as decided with their physician.
Cancer-free survival
The cancer-free survival at five years was 91.1% in the exemestane plus OFS group, versus 87.3% in the tamoxifen plus OFS group, which was a 28% relative reduction in risk. There was a 34% relative reduction in breast cancer recurrence risk in the exemestane plus OFS group compared to the tamoxifen plus OFS group and a 22% relative reduction in distant recurrence (metastasis) risk. The five-year overall survival rates were high in both groups ? 95.9% in the exemestane plus OFS group and 96.9% in the tamoxifen plus OFS group. Longer follow-up is needed to accurately assess the impact of the two treatments on long-term survival.
Acting on results
The side effects were similar to those reported in previous studies comparing adjuvant aromatase inhibitors and tamoxifen in postmenopausal women, and differed depending on the agent. Despite the side effects, only 14% of TEXT and SOFT participants completely stopped the protocol-assigned treatments early ? an adherence rate that is higher than what is seen in everyday practice. Pagani stated that this high compliance rate is important information for doctors who wish to propose this treatment to their patients.
The TEXT and SOFT trials were conducted at the same time and in the same general population ? premenopausal women with hormone receptor-positive early breast cancer. The original plan was to analyze each trial separately as well as jointly, given the common treatment groups of exemestane plus OFS and tamoxifen plus OFS in both trials. However, by combining the trials in a joint analysis, the results could be presented earlier, giving physicians and patients the possible benefit of acting on the results sooner.
Additional treatment options
?Young women with breast cancer have long needed additional treatment options after surgery, and now they may have one,? said 2013 – 2014 ASCO president Clifford A. Hudis, MD, FACP., Chief, Breast Cancer Medicine Service, at Memorial Sloan Kettering, New York, NY. ?Tamoxifen has been a gold standard for decades and has significant benefits. Now, with ovarian suppression, aromatase inhibitors are an option offering a further reduction in the risk of recurrence.?
For more information:
[1] NCT00066703 Triptorelin With Either Exemestane or Tamoxifen in Treating Premenopausal Women With Hormone-Responsive Breast Cancer (TEXT) [Study Record Detail]
[2] NCT00066690 Suppression of Ovarian Function Plus Either Tamoxifen or Exemestane Compared With Tamoxifen Alone in Treating Premenopausal Women With Hormone-Responsive Breast Cancer (SOFT) [Study Record Detail]
[3]Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Lang I, Gomez HL, et al. Randomized comparison of adjuvant aromatase inhibitor (AI) exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): Joint analysis of IBCSG TEXT and SOFT trials. 2014 ASCO Annual Meeting. Plenary Session Time: Sunday June 1, 1:00 PM to 4:00 PM. Abstract No: LBA1 [Abstract]
[4] Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, L?ng I, Gomez HL, Tondini C, et al. Adjuvant Exemestane with Ovarian Suppression in Premenopausal Breast Cancer. N Engl J Med. 2014 Jun 1. [Article][PubMed]
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