While clinical breakthroughs have dramatically extended the life expectancy for women with breast cancer, those with metastatic breast cancer still face a dismal prognosis. Median overall survival hovers at three years and the five-year survival rate remains about 25%. Leading clinicians from 88 countries have developed new guidelines for treatment and management of these challenging patients, which were recently released by the European Society of Medical Oncology.
Many changes focused on estrogen receptor positive (ER+), human epidermal growth factor 2 negative (HER2-) or luminal advanced breast cancer.
The experts acknowledged that few clinical trials included pre-menopausal women with luminal breast cancer, but recommended that these women be “treated in the same way as post-menopausal women, with endocrine agents and with or without targeted therapies,” following suppression or ablation of ovarian function (OFA/OFS).
Doctors walking down hallway. Source: Getty
In regard to clinical trials, they said that “resources should not be wasted running duplicate and separate trials for pre- and post-menopausal patients,” but that younger, pre-menopausal women should be eligible for trials once they have had OFS or OFA. For women who decline OFS or OFA, the panel advocated strongly against “unrealistic, unnecessary and sometimes expensive” clinical trial requirements that mandated use of multiple forms of contraception or complete abstinence for up to six months following completion of the study drug. They noted that tamoxifen monotherapy is the only endocrine option for pre-menopausal women who decline OFS/OFA, but the experts believed it to be a “less effective option.”
Other changes revolved around the use of the cyclin dependent kinase 4/6 (CDK 4/6) inhibitors. Based on studies finding a significant improvement in median progression free survival, the panel recommended adding a CDK 4/6 inhibitor to an aromatase inhibitor as preferred treatments for both endocrine naïve and endocrine exposed patients. Combining a CDK 4/6 inhibitor to fulvestrant was a new preferred treatment option for patients who have previously received endocrine therapy.
Treatment options with lower scores included everolimus plus an aromatase inhibitor for some patients, and everolimus plus tamoxifen or fulvestrant. Patients treated with everolimus should be closely monitored, based on the increase in toxic deaths seen in the BOLERO-2 trials.
The guidelines recommended not using everolimus or CDK 4/6 inhibitors following progression on the specific agent. The panel noted that no validated predictive biomarkers beyond hormone receptor status can identify patients most likely to benefit from the addition of a targeted therapy such as CDK 4/6 inhibitors or mTOR inhibitors to endocrine therapy and said “research efforts must continue” in this area.