NCCN VERSION 2 2015

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MS-49

NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

hormone receptor-negative with disease localized to the bone or soft

tissue only or with asymptomatic visceral disease, irrespective of HER2

tumor status.

For postmenopausal women who are antiestrogen naive or who are

more than 1 year from previous antiestrogen therapy, the options

include either an aromatase inhibitor, selective ER modulator, or an ER

down-regulator. According to some studies, aromatase inhibitors appear

to have superior outcome compared with tamoxifen, although the

differences are modest.

433-436

A Cochrane review has also suggested a

survival benefit favoring the aromatase inhibitors over other endocrine

therapies, although the advantage is small.

437

A randomized phase III

trial comparing tamoxifen and exemestane as first-line endocrine

therapy for postmenopausal women with metastatic breast cancer

showed no significant differences in progression-free survival (PFS) or

OS between the two arms.

435

A randomized phase II study compared

anastrozole versus fulvestrant in over 200 patients with advanced

breast cancer.

438,439

In the initial analysis, fulvestrant was as effective as

anastrozole in terms of overall response (36.0% vs. 35.5%; odds ratio,

1.02; 95% CI, 0.56 –1.87;

= .947) in evaluable patients (n= 89 for

fulvestrant and n=93 for anastrozole).

438

The updated follow-up results

showed an improved time to progression with fulvestrant compared to

anastrazole (median time to progression was 23.4 months for

fulvestrant vs. 13.1 months for anastrozole; HR, 0.63; 95% CI, 0.39–

1.00;

=.0496).

439

This study used a higher 500 mg loading dose every

2 weeks for 3 doses and then 500 mg monthly.

438

Fulvestrant appears

to be at least as effective as anastrozole in patients whose disease

progressed on previous tamoxifen,

440,441

and a reanalysis of these

studies suggests a longer duration of response favoring fulvestrant.

442

phase II study of fulvestrant in postmenopausal women with advanced

breast cancer and disease progression following aromatase inhibitor

therapy documented a partial response rate of 14.3% with an additional

20.8% of patients achieving stable disease for at least 6 months.

443

The

clinical benefit rates of exemestane and fulvestrant observed in a phase

III trial of postmenopausal women with hormone receptor-positive

advanced breast cancer who experienced disease progression on prior

nonsteroidal aromatase inhibitor therapy were comparable (32.2% vs.

31.5%;

= .853).

444

In that study, fulvestrant was administered as a 500

mg loading dose followed by doses of 250 mg on day 14, day 28, and

then monthly. A separate phase III randomized study in

postmenopausal women with metastatic ER-positive breast cancer

compared fulvestrant 500 mg every 2 weeks for 3 doses followed by

500 mg monthly versus fulvestrant 250 mg monthly. The PFS was

superior with the fulvestrant 500 mg regimen (HR 0.80; 95% CI, 0.68–

0.94;

= .006),

445

indicating an increased duration of response with the

higher dose of fulvestrant. The final analyses demonstrated an increase

in median OS (4.1 months) and reduced risk of death (19%) with a dose

of 500 mg compared with 250 mg. Median OS was 26.4 vs. 22.3

months (HR: 0.81; 95% CI: 0.69-0.96;

= .016).

446

Combination endocrine therapy in postmenopausal women with

hormone receptor-positive, previously

untreated

metastatic breast

cancer has been reported from two studies comparing single-agent

anastrozole versus anastrozole plus fulvestrant.

In one study (FACT), combination endocrine therapy was not superior

to single-agent anastrozole (time to progression HR 0.99; 95% CI,

0.81–1.20;

= .91).

447

In the second study (S0226), PFS (HR 0.80; 95%

CI, 0.68–0.94; stratified log-rank

= .007) and OS (HR 0.81; 95% CI,

0.65–1.00; stratified

= .049) were superior with combination

anastrozole plus fulvestrant.

448

An unplanned subset analysis in this trial

suggested that patients without prior adjuvant tamoxifen experienced