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ASCO 2014: Adjuvant Exemestane With Ovarian Function Suppression Better at Preventing Breast Cancer Recurrence Than Tamoxifen

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Key Points

  • Exemestane more effectively prevented breast cancer recurrences than tamoxifen, when either was given with ovarian function suppression to premenopausal women with hormone-sensitive cancers.
  • Exemestane reduced the relative risk of women developing a subsequent invasive cancer by 28% and the relative risk of breast cancer recurrence by 34% compared with tamoxifen plus ovarian function suppression.
  • Five-year overall survival exceeded 95% in both groups, but longer follow-up is needed.

A joint analysis of two phase III trials demonstrated that the aromatase inhibitor exemestane more effectively prevents breast cancer recurrences than tamoxifen when either was given with ovarian function suppression to premenopausal women with hormone-sensitive cancers.

Exemestane plus ovarian function suppression reduced the relative risk of women developing a subsequent invasive cancer by 28% and the relative risk of breast cancer recurrence by 34% compared with tamoxifen plus ovarian function suppression, according to the study’s lead author, Olivia Pagani, MD, Clinical Director of the Breast Unit at the Oncology Institute of Southern Switzerland in Bellinzona, Switzerland, who presented the results at the 2014 ASCO Annual Meeting in Chicago (Abstract LBA1).

The two trials were known as TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) and were led by the International Breast Cancer Study Group in collaboration with the Breast International Group and the North American Breast Cancer Group.

Survival Outcomes

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 and an average age of 43 years. The joint analysis looked at outcomes for 4,690 women randomized to receive exemestane plus ovarian function suppression or tamoxifen plus ovarian function suppression for 5 years.

Five-year disease-free survival was 91.1% in the exemestane plus ovarian function suppression group and 87.3% in the tamoxifen plus ovarian function suppression group. Compared to patients receiving tamoxifen, those receiving exemestane had a 34% relative reduction in breast cancer recurrence risk and a 22% relative reduction in distant recurrence risk.

The 5-year overall survival rates were high in both groups: 95.9% in the exemestane plus ovarian function suppression group and 96.9% in the tamoxifen plus ovarian function suppression group. Longer follow-up is needed to accurately assess the impact of the two treatments on long-term survival.

Chemotherapy Was Optional

Ovarian function suppression was achieved through treatment with the drug triptorelin (Trelstar), surgical oophorectomy, or ovarian irradiation. Some women decided, in consultation with their physicians, to also have chemotherapy, but 1,996 patients did not receive chemotherapy.

“Among these women, more than 97% remained free from breast cancer at 5 years when treated with exemestane plus ovarian function suppression and more than 98% were alive at 5 years,” Dr. Pagani said at the ASCO plenary press briefing. “In our opinion, these results clearly indicate that some premenopausal women with hormone receptor–positive breast cancer may have excellent prognosis when treated with 5 years of highly effective adjuvant endocrine therapy without chemotherapy.”

Adverse Events

Adverse events were similar to those reported in previous studies comparing adjuvant aromatase inhibitors and tamoxifen in postmenopausal women. Grade 3/4 targeted adverse events were reported in 31% of patients receiving exemestane vs 29% of those receiving tamoxifen. Self-reported overall quality of life did not favor either treatment and only 14% of patients completely stopped the protocol-assigned treatments early, an adherence rate considered higher than in everyday practice.

‘Valid Alternative’

According to ASCO, the joint analysis of TEXT and SOFT is the largest study worldwide evaluating adjuvant aromatase inhibitor therapy with ovarian function suppression in young women with breast cancer, and the first to demonstrate the value of such therapy in women with hormone receptor–positive cancer. The original plan had been to analyze each trial separately as well as jointly. Combining the two trials in a joint analysis meant the results could be presented earlier. The design of the SOFT trial also included a tamoxifen alone arm, the results of which are expected later this year.

Aromatase inhibitors have primarily been used in postmenopausal women, because their use requires that women have a low level of estrogen. Ovarian function suppression was used in the trials to emulate the low estrogen levels that naturally occur in menopause.

“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,” Dr. Pagani stated. “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 study was supported in part by Pfizer, Ipsen, the International Breast Cancer Study Group, and the National Cancer Institute, National Institutes of Health. Vered Stearns, MD, reported research funding from Novartis and Pfizer.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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