Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2+ breast cancer in the adaptively randomized I-SPY2 trial.
Amy S ClarkChristina YauDenise M WolfEmanuel F PetricoinLaura van 't VeerDouglas YeeStacy L MoulderAnne M WallaceA Jo ChienClaudine IsaacsJudy C BougheyKathy S AlbainKathleen KemmerBarbara B HaleyHyo S HanAndres Forero-TorresAnthony EliasJulie E LangErin D EllisRachel YungDebasish TripathyRita NandaJulia D WulfkuhleLamorna Brown SwigartRosa I GallagherTeresa HelstenErin RoeschCheryl A EwingMichael AlvaradoErin P CraneMeredith BuxtonJulia L ClennellMelissa PaoloniSmita M AsareAmy WilsonGillian L HirstRuby SinghraoKatherine SteegAdam AsareJeffrey B MatthewsScott BerryAshish SanilMichelle MeliskoJane PerlmutterHope S RugoRichard B SchwabWilliam Fraser SymmansNola M HyltonDonald A BerryLaura J EssermanAngela M DeMichelePublished in: Nature communications (2021)
HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2+ breast cancer, adaptively randomized to T-DM1/P, THP, or a common control arm of paclitaxel/trastuzumab (TH), followed by doxorubicin/cyclophosphamide, then surgery. Both T-DM1/P and THP arms 'graduate' in all subtypes: predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Toxicity burden is similar between arms. Degree of HER2 pathway signaling and phosphorylation in pretreatment biopsy specimens are associated with response to both T-DM1/P and THP and can further identify highly responsive HER2+ tumors to HER2-directed therapy. This may help identify patients who can safely de-escalate cytotoxic chemotherapy without compromising excellent outcome.
Keyphrases
- metastatic breast cancer
- epidermal growth factor receptor
- early breast cancer
- phase iii
- phase ii
- tyrosine kinase
- locally advanced
- glycemic control
- open label
- rectal cancer
- clinical trial
- double blind
- study protocol
- cancer therapy
- placebo controlled
- lymph node
- minimally invasive
- oxidative stress
- stem cells
- low dose
- drug delivery
- polycystic ovary syndrome
- high dose
- high throughput
- young adults
- squamous cell carcinoma
- fine needle aspiration
- chemotherapy induced
- pregnant women
- radiation therapy
- surgical site infection
- anti inflammatory