NCCN VERSION 2 2015

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MS-53

NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

This trial documented superior PFS (11.8 months vs. 5.9 months; HR

0.60;

<.001) favoring bevacizumab plus paclitaxel compared with

paclitaxel alone. A similar trial enrolled 736 patients who were

randomized to treatment with docetaxel and bevacizumab or docetaxel

and placebo.

473

This trial also documented increased PFS in the arm

containing bevacizumab (10.1 months vs. 8.2 months with docetaxel

alone; HR 0.77;

=.006). An additional trial, RIBBON-1, combined

bevacizumab with capecitabine, with a taxane (docetaxel,

nab-paclitaxel), with anthracyclines (FEC, CAF, AC, or EC), or with the

same chemotherapy alone. Results of this trial show a statistically

significant increase in PFS with bevacizumab and capecitabine (8.6

months vs. 5.7 months; HR 0.69;

< .001); and taxane- or

anthracycline- (9.2 months vs. 8.0 months; HR 0.64;

<.001)

containing arms.

474,475

None of these studies demonstrate an increase in

OS or quality of life when analyzed alone or in a meta-analysis

combining the trials.

476

The increase in PFS with bevacizumab is

modest, and appears the greatest in combination with paclitaxel,

especially as reported in an unpublished analysis provided to the

FDA.

477

As with endocrine therapy, sequential responses are often observed

with chemotherapy, supporting the use of sequential single agents and

combination chemotherapy regimens. The current guidelines include

doses and schedules of these single agents and combination regimens

for metastatic breast cancer. Failure to achieve a tumor response to 3

sequential chemotherapy regimens or ECOG performance status of 3 or

greater is an indication for supportive therapy only. In this context,

failure to respond to a chemotherapy regimen means the absence of

even a marginal response to the use of a given chemotherapy regimen.

Response to a chemotherapy regimen followed by progression of

disease is not considered a failure to experience response.

Patients with metastatic breast cancer frequently develop many

anatomically localized problems that may benefit from local irradiation,

surgery, or regional chemotherapy (eg, intrathecal methotrexate for

leptomeningeal carcinomatosis).

HER2-Targeted Therapy for Stage IV or Recurrent Metastatic Disease

Patients with tumors that are HER2-positive may derive benefit from

treatment with HER2 targeted therapy. The panel recommends

selecting patients for HER2-targeted therapy if their tumors are either

positive for HER2 by ISH or 3+ by IHC. HER2 testing recommendations

are described in the guideline. Patients with tumors IHC 0 or 1+ for

HER2 or ISH not amplified have very low rates of HER2-targeted

response, and HER2 targeted therapy.

478

Adequate standardization and

validation of HER2 assays by ISH and IHC used in clinical practice is a

concern, and data suggest that false-positive determinations are

common.

20,21,479-481

Recommendations regarding HER2 testing have

been published.

479,481

First-Line Regimens for HER2-Positive Tumors

The NCCN Panel has categorized HER2 targeting regimens as either

preferred or other.

Preferred First-Line Regimens

A randomized, double-blind, phase III study compared the efficacy and

safety of pertuzumab in combination with trastuzumab and docetaxel

versus trastuzumab and docetaxel as first-line treatment for

HER2-positive metastatic breast cancer.

482

The primary endpoint of the

study was independent assessment of PFS. The secondary endpoints

were PFS assessed by investigator, objective response rate, OS, and

safety. A total of 808 patients were enrolled in this trial.

482

The addition

of pertuzumab provided a statistically significant improvement in PFS