SAN ANTONIO – Premenopausal women with early breast cancer should be offered temporary ovarian suppression during chemotherapy if they wish to remain fertile or avoid early menopause, suggests a meta-analysis of five randomized controlled trials among 873 women reported at the San Antonio Breast Cancer Symposium.
Susan London/Frontline Medical News
Dr. Matteo Lambertini
“Oocyte and embryo cryopreservation are standard strategies for fertility preservation in these patients, meaning increasing the chance of pregnancy after the end of treatment,” said lead author Matteo Lambertini, MD, medical oncologist and ESMO fellow at the Institut Jules Bordet in Brussels. “However, they do not prevent the risk of developing chemotherapy-induced premature ovarian insufficiency, and so patients are still at risk of developing early menopause.”
Data from individual trials of ovarian suppression have been mixed, and its use remains controversial, he further noted. As a result, guidelines from ASCO and ESMO for fertility preservation in cancer patients still consider ovarian suppression to be investigational.
Results of the new meta-analysis, reported in a press briefing and session, showed that, compared with control peers, premenopausal women given a gonadotropin-releasing hormone analog (GnRHa) to suppress ovarian function during breast cancer chemotherapy had a more than one-half reduction in odds of premature ovarian insufficiency and were almost twice as likely to become pregnant after completing their treatment.
“We believe that this strategy should now be considered a standard option to reduce the likelihood of chemotherapy-induced premature ovarian insufficiency and potentially improve future fertility in premenopausal early breast cancer patients who undergo adjuvant or neoadjuvant chemotherapy,” Dr. Lambertini maintained. The analysis and trial participants “remind us that there is a life after cancer and to cure the disease should not be considered enough any more.”
These new data are sufficient to put the controversy to rest, for several reasons, he contended. “First, this is an individual-patient meta-analysis of the five major randomized controlled trials in this setting, so it’s kind of the highest level of evidence that we can reach. Second, it’s very unlikely that we will have new randomized, controlled trials in this setting, and I would say also that, based on the results, it would probably be unethical to run randomized, controlled trials in this setting.”
Susan London/Frontline Medical News
Dr. Carlos L. Arteaga
Press briefing moderator Carlos L. Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, wondered how trials were selected for inclusion in the meta-analysis.
Thirteen trials have been conducted on ovarian suppression in premenopausal patients with breast cancer, and the investigators included the five for which they were able to obtain patient-level data, a subset that contained both positive and negative trials, Dr. Lambertini replied. But findings would likely be the same had all trials been included, given that a 2015 analysis using trial-level data from the 12 trials completed at that time showed very similar results (Ann Oncol. 2015 Dec;26:2408-19).
“Societally, this is a hugely significant issue, but the difference you are showing I have to admit is rather modest,” commented Dr. Arteaga, who is also SABCS codirector and AACR past president. “So what kind of conversation do you have with the patient? Who are the ones who would be the best candidates for this approach?”
“The main message is that giving a GnRHa does not avoid the risk of early menopause in all patients, but still, it decreases significantly the number of patients who have this side effect,” Dr. Lambertini replied.
Two groups are optimal candidates for ovarian suppression, he proposed. “First, the patients who are concerned about developing early menopause and its related side effects, who are not interested per se in having a baby after the end of treatment, but may be preserving ovarian function. [Second], for patients interested in having a baby, so interested in fertility preservation, this strategy can be used after cryopreservation procedures or in patients who have no access, for different reasons, to cryopreservation strategies.”
Another point of view
In the session, attendee Kutluk Oktay, MD, PhD, professor of obstetrics & gynecology and reproductive sciences at Yale University, New Haven, and cochair of ASCO’s guideline committee on fertility preservation said, “I cannot agree with your conclusions based on what you presented to us.”
In particular, he took issue with the exclusion of additional trials in breast cancer as well as trials among patients with other types of cancers. “I’m wondering what the rationale is to limit this to breast cancer because chemotherapy is chemotherapy and ovary is ovary, so underlying disease should not matter. By limiting it to breast cancer, you are leaving out three important studies, all in hematological cancer, with better designs … three negative studies,” he commented.
From a clinical point of view, patients with lymphoma and patients with breast cancer differ greatly, Dr. Lambertini countered: The former are about 20 years younger, on average, and often receive less-granulotoxic chemotherapy. “For these reasons, I don’t believe that mixing these two populations would have been [appropriate] for analysis,” he said. “From a methodological point of view, the studies you have mentioned include overall [fewer] than 150 patients, so it’s a very small proportion in comparison to the data we have in breast cancer.”