Systemic therapy regimens for recurrent unresectable (local or regional) or stage IV (M1) diseasea
Note: All recommendations are category 2A unless otherwise indicated.
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aAssess for germline BRCA1/2 mutations in all patients with recurrent or metastatic breast cancer to identify candidates for PARP inhibitor therapy. While olaparib and talazoparib are FDA-indicated in HER2-negative disease, the panel supports use in any breast cancer subtype associated with a germline mutation. There is lower-level evidence for HER2-positive tumors, therefore category 2A for this setting.
bSee additional considerations for those receiving systemic HER2-targeted therapy (BINV‑Q 4).
cMaintenance trastuzumab/pertuzumab after response (with concurrent endocrine therapy if ER+ and HER2+ metastatic breast cancer).
dTucatinib + trastuzumab + capecitabine is preferred in patients with both systemic and CNS progression in the third-line setting and beyond; and it may be given in the second-line setting.
eFam-trastuzumab deruxtecan-nxki may be considered in the first-line setting as an option for select patients (ie, those with rapid progression within 6 months of neoadjuvant or adjuvant therapy [12 months for pertuzumab-containing regimens]). Fam-trastuzumab deruxtecan-nxki is associated with interstitial lung disease (ILD)/pneumonitis. Regular monitoring for this serious side effect is recommended. For patients with a history of ILD/pneumonitis, there are no data on managing safety or toxicity of this drug in a trial.
fMay be used as an option for third-line and beyond; the optimal sequence for third-line therapy and beyond is not known. If not a candidate fam-trastuzumab T-DM1 could be considered in the second-line.
gMultiple lines of concurrent chemotherapy with anti-HER2 therapy (trastuzumab or a TKI) offer clinical benefit for recurrent unresectable HER2+ metastatic breast cancer and have been studied in phase 2 or 3 trials. Clinical experience suggests frequent clinical benefit for such treatment. However, there are no meaningful data for use of any of these regimens among patients previously treated with pertuzumab-based chemotherapy, ado-trastuzumab emtansine, fam-trastuzumab deruxtecan-nxki, or trastuzumab/capecitabine/tucatinib regimens. Thus, the optimal sequence or true benefit of therapy is not known.
hTrastuzumab given in combination with an anthracycline is associated with significant cardiac toxicity. Concurrent use of trastuzumab and pertuzumab with an anthracycline should be avoided.
iTrastuzumab may be safely combined with all non-anthracycline–containing preferred and other single agents listed on (BINV‑Q 5) for recurrent or metastatic breast cancer.
jAdditional targeted therapy options may be useful in certain circumstances when certain biomarkers are detected as listed in (BINV‑Q 6) for recurrent or metastatic breast cancer.
BRCA1/2=breast cancer genes 1 and 2; CNS=central nervous system; ER+=estrogen receptor-positive; HR=hormone receptor; NCCN=National Comprehensive Cancer Network® (NCCN®); PARP=poly (ADP-ribose) polymerase; TKI=tyrosine kinase inhibitor.
1. Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.4.2023. © 2023 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available.
WARNING: LEFT VENTRICULAR DYSFUNCTION AND EMBRYO-FETAL TOXICITY
The most common adverse drug reactions (>10%) with MARGENZA in combination with chemotherapy are fatigue/asthenia (57%), nausea (33%), diarrhea (25%), vomiting (21%), constipation (19%), headache (19%), pyrexia (19%), alopecia (18%), abdominal pain (17%), peripheral neuropathy (16%), arthralgia/myalgia (14%), cough (14%), decreased appetite (14%), dyspnea (13%), infusion-related reactions (13%), palmar-plantar erythrodysesthesia (13%), and extremity pain (11%).
MARGENZA is a HER2/neu receptor antagonist indicated, in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.
Please see full Prescribing Information, including Boxed Warning.
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