Nick Mulcahy

May 30, 2014

UPDATED // CHICAGO — Early menopause and loss of fertility can be devastating effects of chemotherapy for young women with cancer.

However, the use of the hormone-suppressing drug goserelin (Zoladex, AstraZeneca) during chemotherapy for breast cancer minimized both risks, according to results from a phase 3 study presented here at the 2014 Annual Meeting of the American Society of Clinical Oncology® (ASCO). The chemotherapy regimen used included cyclophosphamide, which can induce ovarian failure.

Dr. Halle Moore

"Premenopausal women beginning chemotherapy for early breast cancer should consider this new option to prevent premature ovarian failure," said lead study author Halle Moore, MD, from the Cleveland Clinic, at a meeting press conference.

The purpose of goserelin, which is administered at the same time as cytotoxic therapy, is to temporarily shut the ovaries down and protect them during chemotherapy, she explained.

It looks like a good strategy.

Only 8% (5 of 66) of the women treated with chemotherapy plus goserelin had premature ovarian failure 2 years after cancer treatments; that rate was 22% (15 of 69) for the women treated with chemotherapy alone (odds ratio [OR], 0.30; P = .04).

Premature ovarian failure, which was the primary end point of the study, was defined as amenorrhea for 6 months and postmenopausal levels of follicle-stimulating hormone (FSH).

All study participants were premenopausal, younger than 50 years, and had stage I to IIIA hormone-receptor-negative breast cancer.

Notably, women with hormone-receptor-positive disease were not eligible for the study.

Goserelin was given as monthly injections starting 1 week before the first dose of chemotherapy. It costs about $500 to $600 per injection, and each patient received 4 injections.

Pregnancies were a secondary end point. Roughly the same number of women reported attempting to conceive in the 2 groups. However, more women treated with chemotherapy plus goserelin than with chemotherapy alone became pregnant (21% vs 11%; OR, 2.45; P = .03).

These pregnancies resulted in 16 women (15%) treated with chemotherapy plus goserelin delivering at least 1 baby, compared with 8 women (7%) treated with chemotherapy alone.

"This is the first demonstration of improved fertility prospects and more successful pregnancies when goserelin was used," said Dr. Moore.

The study from the Southwest Oncology Group, known as Prevention of Early Menopause Study (POEMS), also found goserelin to be safe. It was not associated with an increased risk for either miscarriage or pregnancy termination, according to ASCO press materials.

"This is really a practice changing presentation," said Patricia Ganz, MD, from the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. She moderated the ASCO press conference during which the study was highlighted.

 
This is really a practice-changing presentation.
 

Clinicians can tell young women that ovarian failure, although not totally prevented, can be significantly reduced with goserelin, she said.

The study's senior author echoed this high praise. "I think these findings are going to change our clinical practice," said Kathy Albain, MD, from the Loyola University Medical Center in Chicago, in a press statement.

"This is something I would seriously consider with appropriate patients. There's relatively little downside," said Claudine Isaacs, MD, from the breast cancer program at the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC. She was not involved in the study.

However, in an interview with Medscape Medical News, Dr. Isaacs said she wants to see all the data before making any final determinations.

At the oral presentation of the study, which occurred a day after the press conference, discussant Sharon Giordano, MD, from the University of Texas M.D. Anderson Cancer Center in Houston, said she "would be comfortable offering this option to my patients with estrogen-receptor-negative breast cancer who desire future fertility or prevention of premature menopause."

Dr. Moore and her coauthors also report that 4-year progression-free survival was better with chemotherapy plus goserelin than with chemotherapy alone (89% vs 78%; hazard ratio [HR], 0.49; P =.04), as was 4-year overall survival (92% vs 82%; HR, 0.43; P = .05).

Dr. Isaacs said she does not put much stock in the survival data.

"The numbers are too small to make conclusions about the impact of goserelin on breast cancer survival. I would be very cautious about that," she told Medscape Medical News.

Dr. Giordano also criticized the less-than-targeted patient accrual and resulting smaller study population. "Some uncertainty" exists about the study and the strategy, she acknowledged. "I don't think we can consider these results definitive." Dr. Giordano said that she would relay these "caveats" to patients when she was offering goserelin in conjunction with chemotherapy treatment.

Maintaining patient participation in the trial was a challenge. Originally, 257 patients were enrolled and randomized. Ultimately, there were 218 evaluable patients, but complete primary end point data (premature ovarian failure at 2 years) were only available for 62%. Most of the 83 dropouts were the result of death (n = 29) or lack of data on FSH levels.

Goserelin and similar luteinizing hormone-releasing hormone (LHRH) agonists are known as gonadotropin-releasing hormone superagonists (GnRH agonists).

These medications are widely used to control ovulation timing for infertility procedures, such as in vitrofertilization, according to ASCO press materials. In addition, they are widely used to suppress hormonal activity and, thus, treat advanced prostate and breast cancer.

These agents have been previously studied to assess whether they can prevent chemotherapy-induced loss of ovarian function, said Dr. Moore. However, results have been "inconclusive," she said.

The study was funded by the National Institutes of Health. Some of the study coauthors report financial ties to AstraZeneca.

2014 Annual Meeting of the American Society of Clinical Oncology (ASCO). Abstract LBA505. To be presented May 31, 2014.

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