Adjuvant Triptorelin Helps Preserve Fertility In Breast Cancer Survivors

Phase III PROMISE-GIM6 trial results suggest temporary ovarian suppression with triptorelin during adjuvant chemotherapy confers modest benefits for fertility preservation

medwireNews: Trial findings indicate that premenopausal women with breast cancer have a higher long-term chance of ovarian function recovery with concurrent administration of triptorelin and chemotherapy than with chemotherapy alone.

The 5-year cumulative incidence estimate of menstrual resumption (at least one menstrual cycle within or beyond 1 year after treatment) was 72.6% for 148 women randomly assigned to receive the luteinizing hormone-releasing hormone analogue (LHRHa) in addition to chemotherapy, compared with 64.0% for 133 women receiving chemotherapy alone, with a significant hazard ratio after adjusting for age of 1.48.

The women given triptorelin received 3.75 mg intramuscularly at least 1 week before chemotherapy and every 4 weeks during.

“Our results, together with the findings from the POEMS-SWOG S0230 study indicate that, in addition to fertility preservation strategies such as embryo and oocyte cryopreservation, temporary ovarian suppression with LHRHa is an option to preserve ovarian function in premenopausal women with early stage breast cancer receiving adjuvant chemotherapy”, says researcher Lucia del Mastro, from IST Istituto Nazionale per la Ricerca sul Cancro in Genova, Italy, and team.

The women participating in the study were aged 18 to 45 years and had stage I to III breast cancer and, in contrast to prior studies, the majority (80%) had oestrogen receptor-positive disease, confirming a role for LHRHa in ovarian function preservation in a group of women that the researchers say account for more than 65% of new cases of breast cancer.

Over a median follow-up of 7.3 years, there were 11 pregnancies, eight among women receiving LHRHa and three among women receiving chemotherapy alone, a nonsignificant difference.

Reassuringly, Lucia Del Mastro and colleagues point out that the 5-year disease-free survival rate, although lower among women receiving LHRHa was not significantly so, at 80.5% versus 83.7% among women receiving chemotherapy alone. However, they note in JAMA that the study was not sufficiently powered to make conclusions on this outcome.

The team also addressed the concern that resumption of ovarian function and the subsequent oestrogen production during chemotherapy might negatively affect disease-free survival by allowing initiation of LHRHa at the time of ovarian function restoration as part of endocrine treatment.

This was the case for 69.9% of 92.9% of women with endocrine-sensitive tumours who received adjuvant hormonal therapy. And it is a strategy that Ann Partridge, from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA, says in a related editorial will “be increasingly used for very young patients in the future given recent studies demonstrating the efficacy of this approach.”

She concludes that although the current findings suggest only modest benefits for LHRHa in the prevention of chemotherapy-associated infertility, collectively with those of other studies they offer patients “new treatment and supportive care options […] ultimately providing hope regarding an issue that is highly valued by many young patients diagnosed with cancer.”

References

Lambertini M, Boni L. Michelotti A, et al. Ovarian suppression with triptorelin during adjuvant breast cancer chemotherapy and long-term ovarian function, pregnancies, and disease-free survival. JAMA 2015; 314: 2632–2640. doi: http://dx.doi.org/10.1001/jama.2015.17291

Partridge A. Prevention of premature menopause and preservation of fertility in young cancer survivors. Hopeful though modest long-term results. JAMA 2015; 314: 2625–2627. doi:http://dx.doi.org/10.1001/jama.2015.17299

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