For years, clinicians have relied on endocrine-based therapies to treat postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. Continuing to use these agents on their own may be causing needless deaths today, however.
A recent study, led by researchers at Baylor University in Texas, extended previous findings that targeted therapies combined with endocrine-based therapies work better than endocrine-based therapies alone. They conducted a meta-analysis that demonstrated that the targeted therapy and endocrine-based therapy combinations halve the risk of progression or death compared to monotherapy with endocrine-based agents.
Breast cancer cells. (Source: National Cancer Institute)
The researchers conducted a systematic review of Medline, EMBASE, Cochrane Library and conferences held from 2013 to 2016 to identify relevant randomized clinical trials. Trials included in the analysis enrolled women with HR+/HER2- advanced breast cancer and compared endocrine-based therapy alone to a combination of endocrine-based and targeted therapies. All analyzed studies were published after 2007 and reported at least one of the following endpoints—overall response rate, clinical benefit rate or progression-free survival information. The team calculated relative risk, hazard ratios and 95% credible intervals.
The research team reviewed the efficacy information for first-line treatment separately from that for therapies used following failure with an aromatase inhibitor, which also included patients who failed first-line chemotherapy. Drugs used in the studies included the endocrine-based therapies letrozole, fulvestrant and exemestane. The targeted therapies included the CDK4/6 inhibitors ribociclib and palbociclib as well as the mTOR inhibitor everolimus.
In the first-line setting, three trials reported all three outcomes. In those studies, the researchers determined that patients receiving targeted therapy plus endocrine-based therapy had a 44% longer mean progression-free survival than those receiving only endocrine-based therapy. Patients receiving the combination therapy also had 34% higher overall response rate. The clinical benefit rate was 1.17 favoring the combination therapy.
Three trials compared the combination approach to monotherapy following aromatase inhibitor failure. Of those, two reported progression-free survival and overall response rate. None provided the clinical benefit rate. In this setting as well, the researchers determined that targeted therapy (TT) combined with endocrine-based therapy (ET) performed far better than endocrine-based therapy alone. The combination improved progression-free survival 56% and had 3.5 times the overall response rate compared to endocrine-therapy by itself.
“These results consistently indicate that the hazard of progression or death was approximately halved and that overall response and clinical benefit rates were significantly improved across patient settings for patients receiving TT+ET relative to ET monotherapy among postmenopausal women with HR+/HER2-” advanced breast cancer, the researchers concluded.