Long-term follow-up of a phase III clinical trial shows strong trends toward a greater likelihood of resuming menses and becoming pregnant when a luteinizing hormone-releasing hormone (LH-RH) analog is administered with chemotherapy in patients with breast cancer, according to data released Thursday, September 4, 2014, at the 2014 ASCO Breast Cancer Symposium.
In the PROMISE-GIM6 study, pregnancy was more than twice as likely to occur over 7 years with adjuvant triptorelin compared with chemotherapy without triptorelin, with no difference in disease-free survival, according to presenter Matteo Lambertini, MD, an oncology fellow at San Martino-IST in Genova, Italy.
When considered in tandem with the recent POEMS study, the finding supports the use of LH-RH analogs during chemotherapy in younger patients with early-stage breast cancer who are concerned about fertility and loss of ovarian function, said Lambertini.
Data from POEMS, released during the ASCO 2014 meeting, demonstrated a lower rate of ovarian failure at 2 years (8% vs 22%) and twice the odds of pregnancy (adjusted odds ratio: 2.45) in premenopausal patients with hormone receptor-negative (HR–) breast cancer who were randomized to goserelin beginning at least 1 week prior to the start of and continuing through the end of chemotherapy.
Current guidelines from ASCO and ESMO consider the use of LH-RH analogs as experimental in this setting. “With the POEMS trial and this updated analysis of PROMISE, both ASCO and ESMO should consider updating their recommendations, and consider LH-RH agonists as a strategy to preserve ovarian function and fertility,” he said.
PROMISE-GIM6 was a multicenter, parallel, open-label trial in which 281 women with premenopausal early-stage breast cancer who were candidates for neoadjuvant or adjuvant chemotherapy were randomized to chemotherapy alone (n = 133) or chemotherapy plus triptorelin 3.75 mg intramuscularly every 4 weeks starting at least 1 week before chemotherapy and continuing for the duration of chemotherapy (n = 148).
About 80% of the patients in each arm had HR-positive (HR+) disease. More than 90% of patients received anthracyline-based or anthracycline and taxane-based chemotherapy, which was completed as planned in more than 90% of patients overall. Some 80.4% had endocrine-sensitive tumors and 92.2% received adjuvant endocrine therapy. Premature ovarian failure was defined as no resumption of menstrual activity and postmenopausal levels of both follicle-stimulating hormone and estradiol 1 year after the end of chemotherapy.
One-year results (JAMA
2011;306:269-276) showed a highly significant 72% reduction (8.9% vs 25.9%; P
<.001) in the risk of treatment-related early menopause in patients randomized to chemotherapy plus triptorelin compared with chemotherapy alone, thereby meeting the study’s primary endpoint.
After a median follow-up of 7.3 years, there were 8 pregnancies in the chemotherapy-plus-triptorelin arm versus 3 pregnancies in the chemotherapy-alone arm. The incidence rate of pregnancy was 0.9 per 100 person-years versus 0.4 per 100 person-years in the 2 arms, respectively. The 5-year cumulative incidence estimate of pregnancy was 2.9% in the chemotherapy-plus-triptorelin arm and 1.6% in the chemotherapy-alone arm, for a hazard ratio (HR) of 2.56 (P
= .142), according to Lambertini.
The 5-year cumulative incidence estimate of menstrual resumption at any time was 72.6% in the chemotherapy-plus-triptorelin arm compared with 64.0% in the chemotherapy-alone arm, (HR = 1.28; P
The 5-year disease-free survival was 80.5% in the chemotherapy-plus-triptorelin arm and 83.7% in the chemotherapy-alone arm, for a HR of 1.17 (P
= .519). An exploratory multivariate analysis adjusted for baseline disease stage and hormone-receptor status, “importantly showed no difference in disease-free survival between the 2 treatment arms,” Lambertini said. An exploratory subgroup analysis showed no significant interaction between HR status and disease-free survival.
At the time of the final analysis, 5-year overall survival was 93.3%, with no statistical comparison between treatment arms performed because of the low number of events.
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