As reported in the Journal of the National Cancer Institute, Dr. Lucia Del Mastro of the University of Genova and colleagues analyzed long-term safety data from PROMISE-GIM6, a multicenter, randomized, open-label, phase III superiority trial conducted at 16 Italian centers from 2003 - 2008. Eligible patients were randomized to (neo)adjuvant chemotherapy alone (controls) or combined with the GnRHa triptorelin (GnRHa).
The study met its primary endpoint, showing a statistically significant reduction in the occurrence of chemotherapy-induced premature ovarian insufficiency one year after the completion of cytotoxic therapy. A study update at a median follow-up of 7.3 years showed that GnRHa use during chemotherapy was associated with a higher five-year probability of ovarian function recovery.
The current study reports the final results of the trial at a median follow-up of 12.4 years.
Of 281 randomized patients (median age, 39), 80.4% had hormone receptor-positive breast cancer.
No differences in 12-year disease-free survival (DFS) were seen between the GnRHa arm (65.7%) versus the control arm (69.2%; hazard ratio, 1.16); results were similar for 12-year overall survival (OS) 81.2% versus 81.3% (HR, 1.17).
In patients with hormone receptor-positive disease, the HR was 1.02 for DFS and 1.12 for OS.
Nine patients in the GnRHa arm and four in the control arm had post-treatment pregnancies (HR, 2.14).
Dr. Del Mastro did not respond to requests for a comment, but three US breast cancer experts commented in separate emails to Reuters Health. All three noted that this was a small study but that 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 limits our ability to make conclusions about this group from this clinical trial."
"Importantly," she said, "very few patients in the trial had large breast tumors (more than 5 cm) or a greater number of involved axillary lymph nodes (four or more), so we don't know if these results apply to patients with more locally advanced breast cancers. Additional clinical trials are needed to know how best to treat premenopausal women like these who are at higher risk of cancer recurrence."
Further, she added, the trial was not designed to answer whether this is a good approach for patients wishing to retain fertility after chemotherapy. "The findings suggest that ovarian suppression during chemotherapy may make it more likely that patients can become pregnant, although there are definite limitations, since both older premenopausal patients and patients not interested in becoming pregnant were allowed to enroll in this trial."
"We await data from a different ongoing trial, POSITIVE (https://bit.ly/3dvug20), to hopefully obtain more information about pregnancy after breast cancer," Dr. Henry concluded.
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 showed that GnRHa preserves ovarian function... These data provide another option for women with the most common subtype of breast cancer to maintain ovarian function, manage menopausal side effects, and preserve fertility."
"If women do not seek fertility preservation and are not interested in mitigating early menopause-related symptoms with medication, they would not be candidates for GnRHa during chemotherapy," he noted. "There are a number of nonmedical interventions to manage menopausal side effects."
"Larger studies could clarify the question of whether GnRHa increases the rate of pregnancy," he added. Further, he said, "for patients interested in fertility preservation, GnRH agonist ovarian suppression during chemotherapy is not a substitute for cryopreservation."
Dr. Katherine Crew, also of Columbia University Medical Center, added, "Typically, we will refer these young breast cancer patients to fertility specialists prior to initiating chemotherapy to discuss options for freezing their eggs or embryos, in case they develop chemo-induced menopause."
SOURCE: https://bit.ly/31KQA5e Journal of the National Cancer Institute, online November 25, 2021.
By Marilynn Larkin
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