Ovarian Suppression Drug Can Preserve Fertility After Chemotherapy

Younger women who received the luteinizing hormone–releasing hormone analogue (LHRHa) triptorelin to suppress ovarian function prior to chemotherapy had a greater chance of preserving fertility in the long term, according to a new study published in JAMA.

The phase III, open label PROMISE-GIM6 trial randomized 281 premenopausal women (median age = 39) diagnosed with stage I–III breast cancer to adjuvant chemotherapy or adjuvant chemotherapy plus triptorelin. Trial participants were recruited at 16 sites in Italy and enrolled between 2003 and 2008.

After a median of 7.3 years, 72.6% of the 148 women treated with triptorelin recovered their menstrual cycle compared with 64% of the 133 women in the control group (age-adjusted hazard ratio [HR], 1.48; P = .006).

There was no statistically significant difference in the number of pregnancies in the two study arms. Eight pregnancies (2.1%) occurred in the triptorelin group compared with three (1.6%) in the control group (P = .20). Of the five pregnancies that occurred more than 5 years after the end of chemotherapy, four occurred in the triptorelin arm and one occurred in the control arm.

Treatment with the LHRHa did not affect the 5-year disease-free survival (DFS) rate, which was 80.5% in the triptorelin group compared with 83.7% in the control group (HR, 1.17; P = .52).

A primary analysis of the PROMISE-GIM6 study, published in JAMA in 2011, showed that temporarily suppressing ovarian function with triptorelin during chemotherapy significantly reduced treatment-induced early menopause (from 25.9% in the control arm to 8.9% in the triptorelin arm; P < .001) and reduced the ovarian failure rate at 1 year by 70%.

Embryo and oocyte cryopreservation are the standard fertility preservation options for young women treated for cancer. There is no robust evidence for strategies to preserve ovarian function, and there is some concern that treatment may negatively impact DFS in women receiving endocrine therapy. The current study is the largest randomized, controlled trial to date to test such a strategy.

“In contrast to a number of the prior studies, the trial included predominantly women with estrogen receptor–positive breast cancer (80%) and is thus generalizable to the majority of young women with breast cancer,” wrote Ann Partridge, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School in Boston, in an accompanying editorial.

Seven other studies of hormonal ovarian suppression in breast cancer patients have been published, including the recent Prevention of Early Menopause Study (POEMS) trial that evaluated the LHRHa goserelin.

Results from this and other studies are modest so far, wrote Partridge, yet “collectively these studies reflect the emerging importance of understanding and improving such critical quality-of-life issues.”