A landmark study that was a joint analysis of two phase III trials, TEXT and SOFT, 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.

In the study, exemestane plus OFS reduced the relative risk of women developing a subsequent invasive cancer by 28 percent, and specifically reduced the relative risk of breast cancer recurrence by 34 percent, compared with tamoxifen plus OFS.

“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 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.”

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 US 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 oestrogen.

In the TEXT and SOFT trials, ovarian function suppression was used in premenopausal women to emulate the low oestrogen levels that naturally occur in menopause.

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 randomised 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. 

The cancer-free survival at five years was 91.1 percent in the exemestane plus OFS group, versus 87.3 percent in the tamoxifen plus OFS group, which was a 28 percent relative reduction in risk.

There was a 34 percent relative reduction in breast cancer recurrence risk in the exemestane plus OFS group compared to the tamoxifen plus OFS group and a 22 percent relative reduction in distant recurrence (metastasis) risk.

The five-year overall survival rates were high in both groups ─ 95.9 percent in the exemestane plus OFS group and 96.9 percent in the tamoxifen plus OFS group.

Longer follow-up is needed to accurately assess the impact of the two treatments on long-term survival.

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 percent 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.

Dr. 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 analyzer 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.

Source: ASCO