Role of luteinizing hormone-releasing hormone analog (LHRHa) triptorelin (T) in preserving ovarian function during chemotherapy for early breast cancer patients: Results of a multicenter phase III trial of Gruppo Italiano Mammella (GIM) group.

Abstract

528 Background: To evaluate the role of LHRHa-induced ovarian suppression in preserving the ovarian function (OF) during chemotherapy (CT), a phase III trial was carried out. Methods: Main eligibility criteria: stage I-III premenopausal BC patients (pts), age 18 to 45; hormone receptor (HR) status positive or negative. Arm A: CT alone; arm B: CT + T. T (supplied by Ipsen, Italy) was given every 4 wks during all CT cycles. Allowed CT regimens: CEF or EC (cyclophosphamide, epirubicin, fluorouracil); A (doxorubicin) C; CEF or EC followed by paclitaxel or docetaxel; A or E followed by CMF; CMF. Pts with HR+ tumor received tamoxifen after CT. Primary endpoint: incidence of early menopause (defined by postmenopausal levels of both FSH and estradiol [E2] and no menstrual activity) 1 yr after the end of CT. Study design: multicenter, open-label, randomized, phase III trial. Assuming an incidence of permanent menopause of 60%, for alpha = 0.05 (2-sided) and beta = 0.1 (90% power), 140 pts per arm were needed to detect a 20% absolute reduction in CT+T arm. Results: From Oct 2003 to Jan 2008, 281 pts were randomized: 133 in arm A and 148 in arm B. In both arms median age was 39 and median number of CT cycles was 6. Median cumulative dose of C was 3,840 mg (0-6,930) in arm A and 3,940 mg (0-7,200) in arm B. One yr after CT, early menopause was observed in 43 pts (32.3%; 95% CI 25-41) in arm A and in 20 pts (13.5%; 95% CI 80-91) in arm B (p = 0.0002), with a 19% absolute reduction (95% CI 8-29). Resumption of menstrual activity and/or premenopausal E2 levels was observed in 77 pts (58%; 95% CI 49-66) in arm A and in 114 pts (77%; 95% CI 69-83) in arm B (p = 0.006). Logistic regression analysis confirmed that treatment with T was independently associate with a higher probability of OF preservation (p = 0.001). Conclusions: Temporary ovarian suppression with T during CT is associated with a significant increase in OF preservation in BC pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ipsen