Practical Considerations in Breast Cancer - Episode 11

Upfront Treatment of HR-Positive MBC

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Aromatase inhibitors (AIs) are the first-line standard of care for postmenopausal women with HR-positive advanced breast cancer, states Adam M. Brufsky, MD, PhD. Other treatments are available as upfront therapy; however clinical trials have reported mixed results for these treatments, specifically in regard to the estrogen receptor antagonist fulvestrant.

A phase III trial conducted by SWOG demonstrated an improvement in progression-free survival and overall survival for the combination of fulvestrant and anastrozole in untreated patients with HR-positive metastatic breast cancer. Interestingly, Hope S. Rugo, MD, points out, approximately 40% of patients in this trial had de novo metastatic disease. In a subset analysis, it appeared that the de novo patients benefited the most from the combination therapy, Rugo suggests.

In a separate phase III trial, known as FACT, contradictory data suggested a lack of clinical efficacy for the combination of fulvestrant and anastrozole as a first-line therapy. However, Rugo notes, only 13% of patients enrolled in this study had de novo metastatic breast cancer. Adding to this, following treatment with an AI, the SoFEA trial demonstrated a lack of clinical benefit for the combination of fulvestrant plus anastrozole, Rugo notes. Taken together, these data suggest the combination is most effective in patients with newly diagnosed metastatic breast cancer.

Initially, fulvestrant was used at a 250 mg dose, which was shown to be inferior to the 500 mg dose, notes Mark D. Pegram, MD. This change in dosing may impact the importance of some of the earlier findings, since these studies primarily explored the lower dose. The 500 mg dose appears to be as effective as the combination of 1-mg anastrozole and 250-mg fulvestrant, Pegram adds.

Clinical trials continue to explore the optimization of therapies for patients with HR-positive breast cancer. Combining hormonal therapies with other novel targeted therapies appears to be a promising approach, notes Denise A. Yardley, MD. In general, Kimberly L. Blackwell, MD, notes, regardless of the treatment administered, it is important to treat the patient long enough to induce a response.

To explore the frontline treatment further, the phase III FALCON study is comparing 500-mg fulvestrant to 1-mg anastrozole in postmenopausal women with HR-positive advanced breast cancer who have not received a prior hormonal therapy. This study will help establish whether there is an optimal therapy, notes Joyce A. O’Shaughnessy, MD.