Info
HER2 positive-of-metastatic breast cancer
1st line: Dual anti-HER2 agents: ↑ PFS & ↑ OS
- Docetaxel/trastuzumab/pertuzumab (DHP) vs. DH (CLEOPATRA, NEJM 2012;366:109); or can use weekly paclitaxel-↑ tolerability (T)+HP (JCO 2015;33:442)
- Aim for combination chemo + HP for 6 mos; consider switch to vinorelbine or gem if taxane not tolerate (VELVET2, Oncologist 2017;22:1160)
2nd line
- T-DM1 > lapatinib (L) + cape: ↑ PFS & ↑ OS (EMILIA, NEJM 2012;367:1783)
- Tucatinib + cape + H: ↑ PFS overall, ↑ PFS, & OS in pts w/ brain mets; included pts w/ active/untreated brain mets (HER2CLIMB, NEJM 2020;382:597)
3rd line & beyond
- Trastuzumab-Deruxtecan (T-DXd)—ORR 60%, PFS 12.7-NR (DESTINY-01, NEJM 2020;382:610)
- Margetuximab + chemo-↑ PFS but Δ of 0.9 mos (SOPHIA, JAMA Onc 2021;7(4):573)
- May continue H + other options (ie, chemo or hormone (NCCN 2021, JCO 2018;36:2736)
- Other TKIs: L + Cape (NEJM 2006;355:2733); neratinib + Cape (JCO 2010;28:1124)
- Therapies under development: T-DXd for HER2 “low” (IHC 1-2+), combination anti-HER2, & IO, further development of ADCs
- ER+/PR+/HER2+: Distinct biologic & clinical subtype
- Recommend 1st-line THP given OS benefit, but AI + HP may be appropriate in pts unable to tolerate chemo (PERTAIN, JCO 2018;36:2826)