NCCN VERSION 2 2015

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MS-54

NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

compared to trastuzumab plus docetaxel alone. The median

independently assessed PFS was increased by 6.1 months, from 12.4

months in the control group to 18.5 months in the pertuzumab group

(HR for progression or death, 0.62; 95% CI, 0.51– 0.75;

<.001).

482

At a

median follow-up of 30 months the results showed a statistically

significant improvement in OS in favor of the pertuzumab-containing

regimen, with a 34% reduction in the risk of death (HR, 0.66; 95% CI,

0.52–0.84;

= .0008). The median OS was 37.6 months in the

non-pertuzumab group and had not yet been reached in the

pertuzumab-containing regimen.

167

The most common adverse

reactions reported in the pertuzumab group compared to the control

group were diarrhea, rash, mucosal inflammation, febrile neutropenia,

and dry skin. Peripheral edema and constipation were greater in the

control group.

482

Cardiac adverse events or left ventricular systolic

dysfunction were reported slightly more frequently in the control

group.

483

Health-related quality of life was not different in the two

treatment groups.

484

Phase II trials have also found activity and tolerability for pertuzumab,

pertuzumab with trastuzumab, and for other regimens combining

pertuzumab and trastuzumab together with other active cytotoxics (ie,

paclitaxel, vinorelbine).

485,486

487

Phase III trials of pertuzumab plus

chemotherapy without trastuzumab have not been reported.

The NCCN Panel recommends pertuzumab plus trastuzumab in

combination with a taxane as a preferred option for first-line treatment of

patients with HER2-positive metastatic breast cancer. Pertuzumab plus

trastuzumab in combination with docetaxel is NCCN category 1 and in

combination with paclitaxel is a category 2A recommendation.

Other First-Line Regimens for HER2-Positive Tumors

First-line trastuzumab in combination with selected

chemotherapeutics

228

or as a single agent

227,229

is another option for

HER2-positive metastatic breast cancer patients. Randomized trials

demonstrate benefit from adding trastuzumab to other agents including

paclitaxel with or without carboplatin,

228,478,488,489

docetaxel,

488

and

vinorelbine,

488

or as a single agent

229

for patients with HER2-positive

disease. In addition, the combination of trastuzumab and capecitabine

has also shown efficacy as a first-line trastuzumab-containing regimen

in this population of patients.

490,491

For those patients with hormone

receptor-positive, HER2-positive disease, the panel recommends initial

treatment with endocrine therapy, an approach consistent with most of

these studies. The panel believes the 27% frequency of significant

cardiac dysfunction in patients treated with the combination of

trastuzumab and doxorubicin/cyclophosphamide chemotherapy in the

metastatic setting is too high for use of this combination outside the

confines of a prospective clinical trial.

228,491,492

The NCCN Panel has listed trastuzumab with the following agents:

paclitaxel alone or along with carboplatin; docetaxel; vinorelbine; and

capecitabine as other first-line regimens for patients with HER2-positive

systemic disease.

Regimens for Trastuzumab-Exposed HER2-Positive Disease

The NCCN Panel recommends continuation of HER2 blockade for

patients with HER2-positive metastatic breast cancer that progresses

on first-line trastuzumab-containing regimens. This recommendation

also applies to the new class of patients who are diagnosed with

HER2-positive metastatic disease following prior exposure to

trastuzumab in the adjuvant setting. Several trials have demonstrated

benefit of continuation of trastuzumab therapy following disease

progression on a trastuzumab-containing regimen.

493-495

However, the