How is HER2/neu-positive metastatic breast cancer treated?

Updated: Apr 23, 2020
  • Author: Joseph A Sparano, MD; Chief Editor: John V Kiluk, MD, FACS  more...
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Answer

Answer

First-line cytotoxic therapy should always be given in combination with trastuzumab. [39, 40] Trastuzumab regimens are 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or 8 mg/kg IV on day 1 followed by 6 mg/kg every 3 wk. In patients who have progression after initial therapy, anti-HER2 therapy should be continued by either continuing trastuzumab and changing cytotoxic therapy or switching to lapatinib plus capecitabine.

Preferred first-line single agents with trastuzumab

Regimens are as follows:

  • Paclitaxel 175 mg/m 2 IV on day 1 every 3 wk  or
  • Paclitaxel 80-90 mg/m 2 IV weekly  or
  • Docetaxel 80-100 mg/m 2 IV on day 1 every 3 wk  or
  • Docetaxel 35 mg/m 2 IV weekly  or
  • Vinorelbine 25 mg/m 2 IV weekly  or
  • Capecitabine 1000-1250 mg/m 2 PO BID on days 1-14 every 3 wk

Preferred combination chemotherapy with trastuzumab

Regimens are as follows:

  • PCH: Carboplatin AUC 6 IV on day 1 plus  paclitaxel 175 mg/m2 IV on day 1 every 3 wk plus  trastuzumab (Herceptin) or

  • Weekly PCH: Paclitaxel 80 mg/m2 IV on days 1, 8, and 15 plus  carboplatin AUC 2 IV on days 1,8, and 15 every 4 wk plus trastuzumab

  • Pertuzumab/trastuzumab/docetaxel: pertuzumab 840 mg IV plus  trastuzumab 8 mg/kg IV plus  docetaxel 75 mg/m2 IV on day 1, then  pertuzumab 420 mg plus  trastuzumab 6 mg/kg plus  docetaxel 75 mg/m2 q3 wk (may increase docetaxel to 100 mg/m2 if initial dose well tolerated) [41]

Preferred agents for trastuzumab-exposed patients

Regimens are as follows:

  • Capecitabine 1000 mg/m2 PO BID on days 1-14 plus  lapatinib 1250 mg PO on days 1-21 every 3 wk or

  • Trastuzumab 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or  8 mg/kg IV on day 1 followed by 6 mg/kg every 3 wk plus  other first-line agents or

  • Trastuzumab 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or  8 mg/kg IV on day 1 followed by 6 mg/kg every 3 wk plus  capecitabine 2500 mg/m² on days 1-14 every 3 wk [38, 42] or

  • Trastuzumab 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or  8 mg/kg IV on day 1 followed by 6 mg/kg every 3 wk plus  lapatinib 1000 mg PO daily or

  • Ado-trastuzumab: 3.6 mg/kg IV infusion q3 wk as a single agent in patients who previously received trastuzumab and a taxane, either separately or in combination [43]

  • Trastuzumab deruxtecan: 5.4 mg/kg IV q3 wk as a single agent for unresectable or metastatic HER2-positive breast cancer in adults who have received 2 or more prior anti-HER2-based regimens in the metastatic setting [44]  

  • Trastuzumab 8 mg/kg IV on day 1 followed by 6 mg/kg every 3 wk plus  capecitabine 1000 mg/m2 on days 1-14 every 3 wk plus  tucatinib 300 mg PO BID [45]


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