Developing a prediction model for benefit from fulvestrant in heavily pretreated metastatic breast cancer patients

Introduction

Fulvestrant use in heavily pretreated patients with metastatic breast cancer is associated with highly variable responses. The present study aimed to characterize the benefit of fulvestrant therapy and to develop a prediction model for clinical benefit in this setting.

Methods

A nationwide, retrospective chart review of patients enrolled in a Canadian compassionate use program was performed. This program mandated prior therapy with tamoxifen and both steroidal and nonsteroidal aromatase inhibitors. Charts from the seven highest accruing centers were reviewed. The sample size was based on the derivation of a model to predict the probability of a patient remaining on fulvestrant and free from chemotherapy for at least 3 months.

Results

A total of 305 women received at least one dose of fulvestrant; 207 went on to receive chemotherapy (68%). Of these, 48 (23%) required chemotherapy at 3 months, 113 (55%) at 6 months, and 170 (82%) by 12 months. The median duration of fulvestrant treatment was 126 days (range 23 to 1,920). The median overall survival from start of fulvestrant was 698 days (25th percentile, 316 days to 75th percentile, 1,359 days). The preliminary prediction model showed that older age (OR = 0.96, 95% CI = 0.93 to 0.99) and having received no adjuvant hormonal therapy (OR = 0.5, 95% CI = 0.2 to 1.25) predicted a greater chance of remaining chemotherapy-free at 3 months. Presence of lung (OR = 2.55, 95% CI = 1.1 to 5.9) or brain metastases (OR = 12.8, 95% CI = 4.1 to 55.4) predicted a lower chance of remaining chemotherapy-free at 3 months.

Conclusion

Older age and having received no prior adjuvant hormonal therapy predicted a greater chance of remaining chemotherapy-free at 3 months, while lung and brain metastases predicted a lower chance. These factors may be considered when prescribing fulvestrant.