Medical Technology

Long-term Safety of GnRHa Affirmed in Premenopausal Women Undergoing Chemo for Breast Cancer

NEW YORK (Reuters Health) – In premenopausal women with early breast cancer, use of a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy did not increase the risk of cancer recurrence for up to 12 years, including for those with hormone receptor-positive disease, according to the PROMISE-GIM6 trial.

As reported in the Journal of the National Cancer Institute and Dr. Lucia Del Mastro of the University of Genova and colleagues examined long-term safety results from PROMISE-GIM6, a multicenter, open-label, randomized superiority trial in phase III that was conducted at 16 Italian centers from 2003 – 2008. Patients who were eligible were randomly assigned to either (neo-)adjuvant chemotherapy (controls) or with the GnRHatriptorelin (GnRHa).

The primary goal of the study was met. It showed an statistically significant reduction in the frequency of Ovarian Insufficiency Prematurely Resulting from Chem after one year of treatment. A study update at the median follow-up period of 7.3 years showed that GnRHa treatment during chemotherapy was associated with a greater five-year likelihood of a recovery of ovarian function.

The current study reports the final results of the trial at the median follow-up time of 12.4 years.

In the 281 patients who were randomized (median age, 39), 80.4% were hormone receptor-positive for breast cancer.

No differences in 12-year disease-free survival (DFS) were observed between the GnRHa group (65.7%) versus the control arm (69.2 percent; hazard ratio, 1.16); results were similar for overall survival 12 years later (OS) 81.2% against 81.3 percent (HR, 1.17).

The HR for patients with hormone receptor-positive diseases was 1.02 for DFS, and 1.12 OS.

Nine patients in the GnRHa arm and four in the control arm were pregnant post-treatment (HR, 2.14).

Dr. Del Mastro did not respond to requests for a response, however three US breast cancer experts commented in separate emails to Reuters Health. They all noted that this was a tiny study, but said the results are reassuring.

Dr. N. Lynn Henry, Disease Lead, Breast Oncology at the University of Michigan Rogel Cancer Center in Ann Arbor, noted, “Only one-fifth of patients had estrogen receptor-negative breast cancer, which hinders our ability to draw conclusions about this population from this clinical study.”

She also said that “importantly” she pointed out that “very very few patients in this trial had large breast tumors (more than 5 centimeters) or had axillary lymphodes (four or more). We do not know if the results are applicable to patients with more advanced breast cancers. Further clinical trials are required to know how best to treat premenopausal women such as those at greater risk of recurrence of cancer.”

In addition, she noted, the trial was not designed to answer whether this is a good method for patients looking to maintain fertility following chemotherapy. “The results suggest that ovarian suppression following chemotherapy could increase the chance that patients can become pregnant. However, there are limitations to this trial, since both patients who are not interested in having a baby and those who are older than premenopausal were able to participate.”

Dr. Henry concluded that “We are waiting for results from a different ongoing trial called with a POSITIVE to hopefully get more information on pregnancy following breast cancer.”

Dr. Neil Vasan of the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center in New York City, said, “PROMISE-GIM6 was one of many studies that proved that GnRHa preserves ovarian function… These findings offer a second option for women suffering from the most prevalent subtype of breast cancer to keep their ovarian function intact, control menopausal side effects, and maintain fertility.”

“If women do not desire fertility preservation and are not interested in reducing early menopause-related symptoms with medication and supplements, they are not candidates for GnRHa during chemotherapy,” he noted. “There are a number of non-medical options to treat menopausal-related adverse effects.”

“Larger studies could help clarify the issue of whether GnRHa can increase the likelihood of pregnancy,” he added. In addition, he added “for patients interested in fertility preservation, GnRH antagonist ovarian suppression in chemotherapy is not an alternative to cryopreservation.”

Dr. Katherine Crew, also of Columbia University Medical Center, added, “Typically, we will refer these young breast cancer patients to fertility specialists prior the time they begin chemotherapy to discuss the possibility of freezing their embryos or eggs, in case they develop chemo-induced menopause.”

SOURCE: Journal of the National Cancer Institute, online November 25, 2021.

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