Therapies Given to Women with Advanced Breast Cancer Equally Effective and Safe in Men, Studies Report

Therapies Given to Women with Advanced Breast Cancer Equally Effective and Safe in Men, Studies Report

Current therapies used to treat advanced breast cancer in women are also effective and safe for men with this disease, according to results of three different studies.

These findings were detailed in scientific posters at the European Society for Medical Oncology (ESMO) 2018 Congress that took place Oct. 19–23 in Munich.

About 1 percent of all breast cancer cases occur in men. But male patients are often excluded from clinical trials of breast cancer, and information regarding the effectiveness and safety of current therapies is scarce. Cancer therapy management in men is largely based on what is known and done in women.

Researchers in France analyzed and compared the clinical data —  including treatment, response to treatment, and survival —  of men and women with metastatic breast cancer.

Data were retrieved from the Epidemiological Strategy and Medical Economics Metastatic Breast Cancer (ESME MBC) platform, a national database that collects real-life information on patients newly diagnosed with metastatic breast cancer. Researchers included people who started treatment at 18 French Comprehensive Cancer Centers between January 2008 and December 2014.

Final results were presented in the poster, “Management and outcome of metastatic breast cancer in men in the national multicenter observational ESME program.”

Of the 16,701 evaluable patients, 149 (0.89%) were men. Men were slightly older (mean age of 68.1) than the 16,552 women (mean age of 60.6). More than three-quarters of the men had hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, as did 65.6% of the women.

Results showed that men and women this advanced cancer were given similar treatments.

About 43% of men with HR-positive/HER2-negative metastatic breast cancer received first-line hormonal therapy —  tamoxifen (44.4%), aromatase inhibitor with luteinizing hormone releasing hormone (LHRH) analogues (40.0%), or others (15.5%) —  while 27.6% had chemotherapy as a first-line treatment.

Progression-free survival (PFS), or the time a patient lives without the cancer progressing, was compared between men and women of the same age, breast cancer type, metastasis location, and treatment.

PFS was found to be similar for either type of treatment between these groups, with men and women given hormonal therapy living 9.8 and 13.0 months, respectively, without cancer progression, and 6.9 and 6.3 months on chemotherapy, respectively.

Overall survival for men (41.8 months) was also found to be similar to that of women (34.9 months).

“This new study shows the prognosis of men and women is similar, which is of great value as this justifies our current clinical practice,” Agnes Jager, a medical oncologist and associate professor at Erasmus Medical University Cancer Institute, Rotterdam, The Netherlands, said in a press release.

The next step in this ongoing study will be to assess the frequency of BRCA mutations in men and women, and its association with treatment responses. These results, along with longer-term follow-up, are expected to improve the customized treatment of metastatic breast cancer in men.

The poster “Final analysis of the Male-GBG54 study: a prospective multi-centre phase II study evaluating endocrine treatment with either tamoxifen +/- gonadotropin releasing hormone analogue (GnRHa) or an aromatase inhibitor + GnRHa in male breast cancer patients,” showed the results of the first prospective randomized trial to assess the effectiveness and safety of different hormonal treatments in men with breast cancer.

Since more than 90% of breast cancer in men is hormone receptor positive, therapies used aim at suppressing the hormone-dependent growth of cancer. Tamoxifen — the standard of care in this type of breast cancer — blocks the interaction between estrogen and estrogen receptors in cancer cells, while aromatase inhibitors —  such as Aromasin (exemestane) —  block the production of estrogen itself.

Previous studies have shown the addition of gonadotrophin releasing hormone analogue (GnRHa) to hormonal therapy helps to keep levels of sex hormones — including estradiol, a form of estrogen — in check.

The Phase 3 Male-GBG54 study (NCT01638247) in Germany enrolled 55 men with breast cancer, who were randomized to receive either tamoxifen alone, tamoxifen with GnRHa, or Aromasin with GnRHA.

The results of 46 patients who completed the six-month analysis showed that the levels of estradiol were increased with tamoxifen alone, while the addition of GnRHA to tamoxifen or Aromasin led to a substantial and stable decrease in estradiol levels after three and six months.

Researchers noted that the increased levels of estradiol with tamoxifen were expected, as they are a well-known effect in women. These therapies were also well-tolerated.

Tamoxifen alone was also found to have a small impact on patients’ quality of life and erectile function, while the combination of taxomifen or Aromasin with GnRHa was associated with major adverse effects on both measures.

These findings support the use of tamoxifen alone as a standard hormonal therapy for men with breast cancer, as “the side-effects are moderate, hardly impairing sexual behaviour,” while the addition of GnRH “influenced patients’ well-being and erectile function profoundly,” said Mattea Reinisch, the study’s first author.

The third study, “Ribociclib (RIBO) + letrozole (LET) in male patients (pts) with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC) and no prior endocrine therapy (ET) for ABC: preliminary subgroup results from the phase 2 CompLEEment-1 trial,” showed preliminary results of a Phase 3 trial evaluating the safety and effectiveness of Kisqali (ribociclib) in combination with Femara (letrozole) in breast cancer patients.

Most patients with HR-positive breast cancer become resistant to hormonal therapies, but treatments such as Kisqali — that suppress CDK4/6 molecules — have been shown to help overcome or delay this resistance.

Kisqali, in combination with an aromatase inhibitor (such as Femara) has been approved by the FDA as first-line therapy for all women with HR-positive, HER2-negative advanced or metastatic breast cancer, regardless of their menopausal status.

The Phase 3b CompLEEment-1 trial (NCT02941926) is evaluating the Kisqali-Femara combo therapy in men and in pre- or postmenopausal women with HR-positive, HER2-negative, previously untreated advanced breast cancer. The trial is being conducted in about 525 clinical centers worldwide and is still recruiting participants.

Results presented at the congress focused on the safety findings in 20 men who completed 56 days of follow-up or stopped treatment before the data cut-off.

They showed that the safety profile of Kisqali-Femara combo therapy was similar in men to that seen in women.

The most frequent adverse events reported by these men were hot flushes (30%), neutropenia – low levels of neutrophils, a type of white blood cell – (20%), and constipation (20%). Severe adverse events included neutropenia and increased levels of liver enzymes.

Around 35% of men needed to lower or temporarily stop their doses during that time period, and two withdrew from treatment due to adverse events.

“It is urgent that strategies that have proven effective in defering resistance to endocrine [hormonal] therapy in women are explored in men with advanced breast cancer as well, including CDK4/6 inhibitors [such as Kisqali],” Stefan Zimmerman, MD, with the Centre Hospitalier Universitaire Vaudois in Switzerland, said.

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