NCCN VERSION 2 2015

NCCN Guidelines Version 2.2015 Breast Cancer

NCCN Guidelines Index Breast Cancer Table of Contents Discussion

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; P <.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; P = .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

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