Adjuvant Hormonal Therapy Linked to Improved Outcomes in Ovarian Cancer

Rosalind Eeles, MD, PhD

Adjuvant hormone therapy (AHT) was associated with a 37% reduction in the risk of death in women with epithelial ovarian cancer, according to results of a 24-year study recently published in the Journal of Clinical Oncology (JCO).¹ The therapy was also found to be safe in these patients.

"We were really happy to be able to show that hormone replacement therapy (HRT) is safe for women with the most common type of ovarian cancer. Whether or not to have HRT is a very important decision for a large proportion of women with ovarian cancer, who will often have to undergo the menopause due to the cancer treatment at the same time as coping with a cancer diagnosis,” said lead study author Rosalind Eeles, MD, PhD, professor of Oncogenetics at The Institute of Cancer Research in London.

"Our results not only suggest HRT is safe for women with this type of ovarian cancer, but that it may actually improve their chances of long-term survival. We hope our study will inform treatment for women with ovarian cancer, and the findings could have a big impact on their quality of life," Eeles added.

The phase III, international, nonblinded, randomized trial examined the effects of AHT in 150 pre- and postmenopausal women diagnosed with epithelial ovarian cancer at 9 or fewer months. From 1990 to 1995 patients from 19 centers in the United Kingdom, Spain, and Hungary were randomized 1:1 to either AHT for 5 years (n = 75) or no AHT (n = 75).

Patients were due to start treatment within 2 weeks of random assignment and to continue their treatment for a minimum of 5 years, if tolerated. The median age at random assignment was 58.7 years.

The trial’s primary endpoint was OS and relapse-free survival. Additional trial endpoints included compliance to hormone treatment and recording of selected adverse events, such as myocardial infarction, fracture, transient ischemic attack, cerebrovascular accident, and second cancer.

Of the 75 patients who received AHT, 96% (n = 72) received at least 1 day of treatment after random assignment and 4% of patients (n = 3) received no AHT after random assignment. The types of AHT were conjugated estrogens (n = 38), conjugated estrogens and norgestrel (n = 19), estradiol patch (n = 14), and estradiol implant (n = 1).

The median estimated time receiving AHT for patients allocated to the AHT group was 1.14 years (IQR, 0.46-5.08 years). Of the 75 patients allocated to the control group, 11% (n = 8) received hormone therapy during follow-up.

Median follow-up in living patients was 19.1 years. Patients were observed at 6 and 12 months, and then annually for a maximum of 15 years. Centers were asked at each follow-up visit whether the patient was continuing AHT and the date AHT was stopped, if applicable.

In the AHT arm, 71% of patients (n = 53) have died compared with 91% (n = 68) of patients in the control arm.

OS was significantly improved in patients who received AHT (HR, 0.63; 95% CI, 0.44-0.90; P = .011). For relapse-free survival, a similar effect was reported (HR, 0.67; 95% CI, 0.47-0.97; P = .032).

Treatment was discontinued for various reasons, including adverse events (n = 14), recurrence/progressive disease (n = 6), patient choice (n = 4), long duration (n = 4), and second primary (n = 2), with some patients seeming to have continued receiving AHT throughout trial follow-up.

“HRT does not seem to have a detrimental effect on survival in women with epithelial ovarian cancer, and there is even the intriguing suggestion that it may be improving their survival chances. We would like to see more research into this area in the future and hope to see other studies confirm this finding in larger numbers of women," study scientific lead Judith Bliss, MSc, professor, director of the Cancer Research UK-funded Clinical Trials and Statistics Unit at the Institute of Cancer Research, said in a statement.

“Eeles et al are to be congratulated for recognizing the importance of this study and observing the accrued cohort for nearly two decades,” Stanley Liplowitz, MD, and Elise C. Kohn, MD, wrote in an editorial published simultaneously in JCO.²

“These findings, unlikely to be repeated, support the hypothesis that HRT improves outcomes in patients with ovarian cancer by reducing ovarian cancer relapse, ovarian cancer-specific death, and other causes of death. In the Women's Health Initiative study, estrogen did not significantly affect all-cause mortality, making the decrease in mortality in the patients studied here of interest,” Liplowitz and Kohn wrote.

These findings demonstrate that women with severe menopausal symptoms following ovarian cancer treatment are able to safely receive AHT and have survival and quality-of-life benefits, the authors noted.

“Where do we stand in 2015? To treat or not to treat?” Lipkowitz and Kohn wrote. “Although there are many unanswered questions […] the data from Eeles et al combined with that of previous studies allow oncologists to feel comfortable offering patients HRT after the treatment of EOC to reduce vasomotor and other postmenopausal symptoms and should, therefore, improve the quality of life for patients with epithelial ovarian cancer.”

1. Eeles RA, Morden JP, Gore M, et al. Adjuvant hormone therapy may improve survival in epithelial ovarian cancer: results of the AHT randomized trial. J Clin Oncol. 2015;33(35):4138-4144.
2. Lipkowitz S, Kohn EC. To treat or not to treat: the use of hormone replacement therapy in patients with ovarian cancer. J Clin Oncol. 2015;33 (35):4127-4128.