Fulvestrant in HR-Positive Breast Cancer

The FIRST trial was a phase II open-label study that demonstrated improvement in survival with fulvestrant over anastrozole in previously untreated individuals with advanced hormone receptor (HR)-positive breast cancer. In the study, treatment with fulvestrant improved overall survival (OS) by 5.7 months compared with anastrozole in postmenopausal women. The median OS was 54.1 months with fulvestrant compared with 48.4 months with anastrozole (HR = 0.70; P = .041).

Despite improvements in disease control and overall survival, clinicians do not expect these early results to alter the current standard of care. Over the last few years it has become clear that findings from a randomized phase II trial do not always tell the whole story, Edith Perez, MD, suggests.

The mechanism of action with estrogen receptor antagonists together with the data from the FIRST trial suggests that fulvestrant may be effective in individuals with tumors that have progressed after estrogen deprivation with an aromatase inhibitor. It is for this reason that clinical studies in breast cancer are increasingly evaluating fulvestrant, rather than an aromatase inhibitor, in combination with other therapies, says Carlos L. Arteaga, MD.

In addition to the frontline setting, fulvestrant is also being studied in patients whose cancer has progressed following endocrine therapy. The PALOMA-3 trial examined fulvestrant plus placebo or palbociclib in pretreated patients with HR-positive, HER2-negative breast cancer. In this study, the combination of fulvestrant and palbociclib demonstrated a median progression-free survival of 9.2 versus 3.8 months in the placebo arm (HR = 0.42; P <.000001). At the time of the analysis, OS data were not yet mature.

Relapse rates in individuals with estrogen receptor (ER)-positive early stage breast cancer remain high, notes Adam Brufsky, MD, PhD. With current treatments, approximately half of the patients will relapse between years 5 and 10, adds Brufsky. This observation has led to extended endocrine therapy, which began more than 10 years ago with the use of letrozole therapy following 5 years of tamoxifen treatment. Today, tamoxifen therapy may also be extended to 10 years instead of 5 years.

In May 2014, the ASCO clinical practice guideline was updated to recommend treatment with adjuvant tamoxifen for 10 years in women with stage I-III HR-positive breast cancer, based on data from the collection of 5 clinical trials showing a reduction in recurrence rates. The most difficult aspect of longer treatment is the adverse events, including the assessment, management, and conversation regarding these events, notes Denise A. Yardley, MD.