Fulvestrant in women with advanced breast cancer after progression on prior aromatase inhibitor therapy: North Central Cancer Treatment Group Trial N0032.
OBJECTIVE
Fulvestrant is an antiestrogen that leads to estrogen receptor degradation and has demonstrated efficacy in breast cancer patients who have had disease recurrence or progression after tamoxifen. This study was designed to examine the efficacy and toxicity of fulvestrant in patients with disease progression on a third-generation aromatase inhibitor (AI).


METHODS
A one-stage phase II trial was conducted in postmenopausal women with measurable disease by Response Evaluation Criteria in Solid Tumors criteria who experienced disease progression after treatment with a third-generation AI and, at most, one additional hormonal agent. Tumors must have been estrogen receptor and/or progesterone receptor positive. The primary end point was objective response rate, and secondary end points were time to disease progression, survival, duration of response, and toxicity.


RESULTS
Eighty patients were enrolled, and three were ineligible. Characteristics of the 77 eligible patients included median age of 68 years, performance score of 0 or 1 in 91% of patients, visceral dominant disease in 88% of patients, two prior hormonal treatments in 73% of patients, and prior chemotherapy for metastatic disease in 32% of patients. Eleven patients (14.3%) achieved a partial response, and 16 patients (20.8%) had stable disease for at least 6 months, for a clinical benefit rate of 35%. Antitumor activity seemed to be higher in women with prior treatment with AI alone compared with women whose prior treatment also included tamoxifen. Median time to progression was 3 months, and median survival time was 20.2 months. Fulvestrant was well tolerated.


CONCLUSIONS
Fulvestrant is a well-tolerated treatment and has efficacy against breast cancers that have progressed after therapy with a third-generation AI.
Ingle
James N
JN
Division of Medical Oncology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. ingle.james@mayo.edu
Suman
Vera J
VJ
Rowland
Kendrith M
KM
Mirchandani
Deepu
D
Bernath
Albert M
AM
Camoriano
John K
JK
Fishkin
Paul A S
PA
Nikcevich
Daniel A
DA
Perez
Edith A
EA
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D020847:Estrogen Receptor Modulators; D000077267:Fulvestrant; D004958:Estradiol