The American Society of Clinical Oncology has issued new guidelines for endocrine therapy for women with hormone receptor–positive metastatic breast cancer.
The consensus recommendations note that hormonal therapy should be offered to patients whose tumors express any level of estrogen and/or progesterone receptors, and that endocrine therapy should be recommended as initial treatment for all patients with hormone receptor–positive (HR+) metastatic breast cancer (MBC), with treatment continued until unequivocal evidence of disease progression, except for those patients who have immediately life-threatening disease or who develop rapid recurrence of the disease in the viscera during adjuvant endocrine therapy.
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The use of combined endocrine therapy and chemotherapy is not recommended.
The guidelines also state that first-line therapy for postmenopausal women should include aromatase inhibitors (AIs), and that, for patients with metastatic breast cancer with no prior exposure to adjuvant endocrine therapy, combination hormone therapy with a nonsteroidal AI and fulvestrant 500 mg with a loading schedule may be offered.
“Premenopausal women with HR-positive MBC should be offered ovarian suppression or ablation and hormone therapy, because contemporary hormonal agents have only been studied among postmenopausal women,” Dr. Hope S. Rugo of the University of California, San Francisco, and other members of the expert panel caution (J Clin Oncol. 2016 May 23. doi: 10.1200/JCO.2016.67.1487).
For second-line therapy, the guidelines recommend sequential hormone therapy for patients with endocrine responsive disease, except in women for whom there is rapid progression with organ dysfunction.
Fulvestrant, when administered, should be given with the 500-mg dose and with a loading schedule at treatment start, days 15 and 28, and then once monthly.
The guidelines, developed after the ASCO expert panel conducted a systematic review of evidence from 2008 through 2015, also mention targeted therapy combinations for specific circumstances:
• A nonsteroidal AI and palbociclib (Ibrance) for postmenopausal women with treatment-naive HR-positive MBC, because of an advantage in progression-free survival (PFS) but not overall survival, compared with letrozole (Femara) alone.
• Exemestane (Aromasin) and everolimus (Afinitor) for postmenopausal women with HR-positive MBC who experienced progression during prior treatment with nonsteroidal AIs with or without one line of prior chemotherapy, either before or after treatment with fulvestrant. This combination showed a PFS but not an overall survival advantage, compared with exemestane alone.
• Fulvestrant and palbociclib for patients who experienced progression during prior treatment with AIs with or without one line of prior chemotherapy (PFS improved, compared with fulvestrant alone). The guidelines caution that treatment should be limited to those without prior exposure to cyclin-dependent kinase 4/6 inhibitors.
• Human epidermal growth factor receptor–targeted therapy should be added to a first-line AI in patients with HR- and HER2-positive metastatic disease for whom chemotherapy is not immediately indicated.
“Genomic or expression profiling should not be used at this time to select treatment for HR-positive MBC,” the authors state.
The guidelines also emphasize that it is “mandatory for all patients to have ER and HER2 status determined in their cancers. Often a biopsy is recommended to determine or confirm whether a suspicious lesion represents MBC; in this case, markers should be obtained.”