Second-Line Therapy
➤ The choice of second-line hormone therapy should take into account prior
treatment exposure and response to previous endocrine therapy (Strong
Recommendation; EB-B-H).
➤ Sequential hormone therapy should be offered to patients with
endocrine-responsive disease (Options are shown in Figure 1.) (Strong
Recommendation; EB-B-H).
Targeted Therapy
➤ Exemestane and everolimus may be offered to postmenopausal women
with HR+ MBC who experience progression during treatment with
nonsteroidal AIs, either before or after treatment with fulvestrant,
because PFS but not overall survival was improved compared with
exemestane alone. (Other options are shown in Figures 1 and 2.)
(Strong Recommendation; EB-B-H).
• This combination should NOT be offered as first-line therapy for patients who
experience relapse >12 months from prior nonsteroidal AI therapy or for those who
are naïve to hormone therapy.
➤ A nonsteroidal AI and palbociclib may be offered to postmenopausal women
with treatment-naïve HR+ MBC. PFS but not overall survival was improved
compared with the nonsteroidal AI letrozole alone (Other options are shown
in Figures 1 and 2.) (Moderate Recommendation; EB-B-I).
• Palbociclib may also be offered in combination with fulvestrant in patients exposed
to prior hormone therapy and up to one line of chemotherapy, on the basis of data
from the phase III PALOMA-3 trial. Progression-free survival (PFS) was improved
compared with fulvestrant alone; overall survival data are immature.
➤ Genomic or expression profiling should NOT be used to select treatment
for HR+ MBC (Moderate Recommendation; CB-B-L).
➤ The addition of HER2-targeted therapy to first-line AIs should be
offered to patients with HR+, HER2+ MBC in whom chemotherapy is not
immediately indicated (Strong Recommendation; EB/CB-B-H).
• The addition of HER2-targeted therapy to first-line AIs improved PFS, without a
demonstrated improvement in overall survival. HER2-targeted therapy combined with
chemotherapy resulted in improvements in overall survival and is the preferred first-
line approach in most cases.
➤ Fulvestrant and palbociclib may be offered to patients who experienced
progression during prior treatment with AIs with or without one line
of prior chemotherapy, because PFS was improved compared with
fulvestrant alone.
• Treatment should be limited to those without prior exposure to cyclin-dependent
kinase 4/6 inhibitors.
Treatment
