AT ESMO 2016

COPENHAGEN (FRONTLINE MEDICAL NEWS) – Fulvestrant continues to show superiority over anastrozole in treatment of hormone receptor-positive breast cancer, particularly in women with lower-volume disease, reported investigators in the phase III FALCON trial.

At a median follow-up of 25 months, median progression-free survival (PFS) for women assigned to receive the selective estrogen-receptor degrader fulvestrant (Faslodex) was 16.6 months, compared with 13.8 months for women assigned to receive the aromatase inhibitor anastrozole (Arimidex), reported Matthew J. Ellis, PhD, of the Lester and Sue Smith Breast Center at Baylor College of Medicine in Houston.

“These results are consistent with data from the FIRST study and confirm that fulvestrant is more efficacious than anastrozole in postmenopausal women with hormone receptor–positive locally advanced or metastatic breast cancer who have not received prior endocrine therapy,” he said at the European Society for Medical Oncology Congress.

The benefit of fulvestrant appeared to be only among patients who did not have visceral metastases, however.

In the FIRST study , results of which were reported at the San Antonio Breast Cancer Symposium in 2014, median overall survival at a median follow-up of 48.8 months was 54.1 months in patients on fulvestrant, vs. 48.4 months with anastrozole (hazard ratio [HR] 0.70, P = .04). The median PFS durations were 23.4 months vs. 13.1 months, respectively (HR 0.66, P = .01).

The FALCON (Fulvestrant and Anastrozole Compared in Hormonal Therapy-Naive Advanced Breast Cancer) trial was a phase III study designed to confirm the PFS benefit seen with fulvestrant in the earlier trial.

Postmenopausal women with locally advanced or metastatic breast cancer positive for the estrogen and/or progesterone receptor and negative for HER2 who had not previously received endocrine therapy were enrolled. They were randomly assigned to receive fulvestrant 500 mg intramuscularly on days 0, 14, and 28 then every 28 days plus an anastrozole placebo (232 patients), or oral anastrozole 1 mg daily plus fulvestrant placebo (230 patients).

Women with life-threatening visceral metastases, systemic estrogen-containing hormone replacement therapy within 6 months of randomization, or prior systemic treatment for breast cancer other than one line of chemotherapy or radiotherapy within 28 days of randomization (except radiation for control of bone pain) were excluded.

As noted, the primary endpoint of PFS was 16.6 months in the fulvestrant arm vs. 13.8 months in the anastrozole arm, translating into an HR for progression on fulvestrant of 0.797 (P = .0486).

Among the 208 patients with no visceral disease, median PFS with fulvestrant was 22.3 months, vs. 13.8 months (HR 0.59, P less than .01). In contrast, among the 254 patients with visceral disease, the respective median PFS durations were 13.8 and 15.9 months (nonsignificant).

For the secondary endpoint of overall survival, at 31% maturity (longest follow-up out to 39 months), there was no significant difference between the study arms.

There were also no significant differences in the secondary endpoints of overall response rate (among patients with measurable disease at baseline), clinical benefit rate, median duration of response, median duration of clinical benefit, or median time to deterioration of total score on the Functional Assessment of Cancer Therapy–Breast (FACT-B) patient-reported outcomes instrument.

Only estimated duration of response (11.4 vs. 7.5 months) and estimated duration of clinical benefit (21.9 vs. 17.5 months) were significantly better with fulvestrant (P less than .001 for each).

The most common adverse events were arthralgia, occurring in 16.7% of patients on fulvestrant vs. 10.3% on anastrozole, and hot flushes/flashes occurring in 11.4% vs. 10.3%, respectively.

Grade 3 or greater adverse events occurred in 22.4% vs. 17.7%. Deaths from adverse events occurred in six patients on fulvestrant vs. seven on anastrozole. None of these deaths were considered to be related.

The FALCON results, which showed a benefit for fulvestrant only for those patients without visceral disease, point to a need for investigating whether patients with visceral metastases should receive other therapies, but this observation is hypothesis-generating only, said invited discussant Peter Schmid, MD, PhD, of Barts Cancer Institute at St. Bartholomew’s Hospital at Queen Mary University of London.


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