Predicting benefit from fulvestrant in pretreated metastatic breast cancer patients

Abstract

Fulvestrant use in pretreated metastatic breast cancer patients is associated with variable response rates. This study aimed to characterize these responses and to develop a prediction model to identify those patients who could potentially derive the most clinical benefit. A nationwide review of patients enrolled in a Canadian compassionate use program from 1999 to 2006 was performed. Prior therapy with tamoxifen, steroidal, and nonsteroidal aromatase inhibitors was mandatory. The dependent variable in the analysis was the proportion of patients requiring chemotherapy at 3 months following the start of fulvestrant. General Linear Mixed modeling was used to identify factors significantly associated with this dependant variable and to subsequently develop the prediction model. Three hundred and five women received at least one dose of fulvestrant; 207 went on to receive chemotherapy (68%). Median duration of fulvestrant treatment was 4.1 months (range 0.8-63.1). Factors predictive of being chemotherapy free at 3 months included older age, no prior adjuvant hormonal therapy, and the absence of lung or brain metastases at the start of therapy. A receiver operating characteristic (ROC) curve analysis had an area under the curve of 0.70 (95% CI 0.60-0.80). This model was able to identify risk information that could be helpful in assessing which patients would most likely benefit from fulvestrant as an intervention with the objective being a delay in chemotherapy.

Metastatic breast cancer patients with lung or liver metastases should be distinguished before being treated with fulvestrant

“…17 In clinical practice, patients with visceral metastases are more likely to receive initial chemotherapy 11 ; however, ER-positive MBC patients are more likely to respond to hormonal therapy when it is administered before chemotherapy. 18 Our results reflect a similar conclusion, with patients who had not received prior chemotherapy for MBC exhibiting a significantly longer median PFS than those who had received prior chemotherapy.…”

Generating Evidence from Expanded Access Use of Rare Disease Medicines: Challenges and Recommendations

“…Through our correspondence with regulators, we learned that Sweden does not allow data collection at all, and that Canada does not “condone” data collection. Nevertheless, several publications on expanded access programs originate from Austria, Sweden, Belgium, and Canada ( Steger et al, 2005 ; Lyckegaard et al, 2007 ; Chen et al, 2009 ; Freedman et al, 2009 ; Bracarda et al, 2015 ; Winqvist et al, 2019 ; Servais et al, 2020 ; Schubert et al, 2021 ). These paradoxes demonstrate the unclear position of expanded access in evidence generation.…”