Addition of triptorelin to chemotherapy preserved long-term ovarian function

The addition of a luteinizing hormone-releasing analog to chemotherapy preserved long-term ovarian function in premenopausal women with early-stage breast cancer, according to long-term results of the PROMISE-GIM6 trial presented at the Breast Cancer Symposium.

“Moreover, this technique seems to improve the chance of becoming pregnant and does not negatively affect prognosis of patients,” Matteo Lambertini, MD, of the department of medical oncology at U.O. Oncologia Medica 2 in Italy, and colleagues wrote.

Several randomized trials designed to assess whether luteinizing hormone-releasing (LHRH) analogs effectively preserve ovarian function during cytotoxic treatments in patients with breast cancer yielded conflicting results. ASCO and ESMO guidelines consider the strategy experimental due to the lack of long-term data on ovarian function and pregnancy rates. Safety concerns about the approach also persist, particularly in younger patients who have endocrine-sensitive tumors, according to background information provided by researchers.

PROMISE-GIM6 — a randomized, multicenter, open label phase 3 trial — included 281 premenopausal women with stage I through stage III breast cancer who were candidates for adjuvant or neoadjuvant chemotherapy.

Lambertini and colleagues randomly assigned 148 patients to chemotherapy plus the LHRH triptorelin. Triptorelin was administered intramuscularly in 3.75-mg doses every 4 weeks, administered at least 1 week prior to chemotherapy, followed by every 4 weeks for the duration of chemotherapy. The other 133 patients received chemotherapy alone.

The percentage of women with hormone receptor-positive disease was comparable between arms (79% vs. 82%), as were other patient and tumor characteristics. Researchers reported 226 patients (80.4%) had endocrine-sensitive tumors, and most of them (92.2%) underwent endocrine therapy after chemotherapy.

Early results of PROMISE-GIM6 showed the use of triptorelin during chemotherapy significantly reduced occurrence of chemotherapy-induced early menopause in this patient population.

The long-term analysis was designed to evaluate long-term ovarian function, pregnancies and DFS.

Median follow-up for the current analysis was 7.3 years (interquartile range, 6.3-8.2).

At the conclusion of adjuvant treatment, eight pregnancies occurred in the combination arm and three occurred in the chemotherapy alone arm. That equated to a 5-year cumulative incidence estimate for pregnancy of 2.9% in the combination arm and 1.6% in the chemotherapy alone arm (HR=2.56; 95% CI, 0.68-9.6).

Menstrual resumption at any time occurred in more patients who received triptorelin (116 vs. 96). That equated to a 5-year cumulative incidence estimate of 72.6% in the combination arm and 64% in the chemotherapy alone arm (HR=1.28; 95% CI, 0.98-1.68).

At study cut-off, the researchers had observed comparable rates of unfavorable events among patients assigned the combination (24.3%) and those who received chemotherapy alone (21.8%).

Researchers observed longer 5-year DFS in the chemotherapy alone arm (83.7% vs. 80.5%). However, multivariate analysis — adjusted for hormone receptor status and baseline disease stage — showed the difference in DFS between arms was not statistically significant (HR=1.1; 95% CI, 0.67-1.8).

“So far, LHRH analogs should be considered an option to preserve ovarian function and fertility and should be proposed to all young women with breast cancer [who are] candidates [for] chemotherapy and concerned about fertility and ovarian function loss due to oncologic treatments.”

For more information:

Lambertini M. Abstract #105. Presented at: Breast Cancer Symposium; Sept. 4-6, 2014; San Francisco.

Disclosure: The researchers report no relevant financial disclosures.