“The simple questions are whether ovarian function suppression adds clinical benefit in premenopausal women, and is ovarian function suppression better with an aromatase inhibitor or tamoxifen,” said formal discussant of these trials, Ann H. Partridge, MD, MPH, FASCO, Professor of Medicine at Harvard Medical School and medical oncologist at Dana-Farber Cancer Institute, Boston.
“With longer follow-up, the SOFT trial is now a positive study. Ovarian function suppression with tamoxifen or exemestane improves disease-free survival vs tamoxifen alone. Ovarian function suppression was favored in all subgroups and treatment groups, and the hazard ratio was greatest in the young patients at highest risk,” Dr. Partridge noted.
“In the whole cohort, there was a small distant recurrence and suggestion of a survival advantage for ovarian function suppression, with the bulk of the benefit in the group that got prior chemotherapy. In the group that did not get chemotherapy, the risk of recurrence and death remains low in all treatment groups,” she said.
Moving on to the combined analysis of the TEXT and SOFT trials, disease-free survival remains highest with an aromatase inhibitor -(exemestane) plus ovarian function suppression in all treatment groups, she said. There is a 4% absolute improvement in disease-free survival with exemestane vs tamoxifen in women treated with ovarian function suppression, which is similar to that seen in postmenopausal women at 10 years.
“It is reassuring that overall survival was similar in both arms in the combined analysis,” Dr. Partridge added. “But why is there no survival benefit for the aromatase inhibitor? This may be due to higher discontinuation rates in that arm.”
It is noteworthy that the effect of exemestane and ovarian function suppression was stronger in HER2-negative patients, but this subset analysis should be “interpreted with caution” and needs further study, she said.
“What happens Monday morning when we go back to clinical practice? I don’t think ovarian function suppression should be given to every patient with HER2-positive disease, especially those who are low risk,” she stated.
‘No Free Lunch’
“There is no free lunch. Adding ovarian function suppression added expected toxicities, and there are long-term morbidities associated with suppressing ovarian function,” she noted, mentioning a recent study of patients who had bilateral oophorectomy and suffered more multimorbidity, including depression, hyperlipidemia, coronary artery disease, and osteoporosis, particularly in women younger than 45.
“We need to be cautious and must follow these women [who had ovarian function suppression] further out. It would be a crime not to. We need to be aware of risks and share them with primary care providers. These women should be screened for potential comorbidities they may be at risk for,” Dr. Partridge cautioned.
“Ovarian function suppression can be considered for higher-risk patients. HER2 status alone should not drive the decision…. For patients who opt for ovarian function suppression, aromatase inhibitor may be preferable, but tamoxifen is still an option. Ovarian function suppression is not likely to be worth it for lower-risk tumors,” she said.
“Treatment should be based on patient preference and tolerance. The best treatment is the one the patient will take,” she concluded. ■
DISCLOSURE: Dr. Partridge reported no conflicts of interest.
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