Neoadjuvant ado-trastuzumab emtansine (T-DM1) combined with pertuzumab substantially improved pathologic complete response rates compared with paclitaxel plus trastuzumab as treatment for women with human epidermal growth factor 2 (HER2)-positive invasive breast cancer,  a study presented at the American Academy for Cancer Research (AACR) Annual Meeting 2016 has shown.1

Because pathologic complete response is a prognostic biomarker for aggressive HER2-positive breast cancer, researchers sought to evaluate whether T-DM1 plus pertuzumab, without paclitaxel, improves pathologic complete response rates vs standard therapy.

For the phase 2 I-SPY 2 trial, researchers enrolled 83 patients with HER2-positive invasive breast cancer whose tumors were 2.5 cm or larger. Participants were randomly assigned 2:1 to receive T-DM1 plus pertuzumab or paclitaxel plus trastuzumab for 12 weekly cycles. Then, all patients received doxorubicin and cyclophosphamide for 4 cycles, followed by surgery.

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Results showed that among patients with HER2-positive disease, the estimated pathologic complete response rate was 52% (95% CI, 36 – 68) for T-DM1 plus pertuzumab compared with 22% (95% CI, 5 – 39) for paclitaxel plus trastuzumab. In patients with HER2-positive, hormone receptor (HR)-positive breast cancer, the estimated rates were 46% (95% CI, 26 – 66) vs 17% (95% CI, 0 – 34), respectively, and 64% (95% CI, 39 – 88) vs 33% (95% CI, 6 – 59), respectively, among patients with HER2-positive, HR-negative disease.

Further, researchers determined that the probability of T-DM1 plus pertuzumab being superior to the control arm was 99.5%, 99.1%, and 98% for HER2-positive disease, HER2-positive, HR-positive disease, and HER2-positive, HR-negative disease, respectively.

“This could, in turn, result in fewer women developing recurrent, metastatic breast cancer without the short- and long-term toxicity of taxane therapy,” said lead author Angela DeMichele, MD, MSCE, professor of medicine and epidemiology at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, PA.

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Although these findings are encouraging, a phase 3 confirmatory study is necessary.

“In addition, since pertuzumab received accelerated approval in the neoadjuvant setting, many patients now receive a taxane with both trastuzumab and pertuzumab (THP). The THP regimen was also tested in ISPY2, and is also superior to standard paclitaxel and trastuzumab,” Dr DeMichele said. “Though we found both T-DM1 plus pertuzumab and the THP regimen to be superior to paclitaxel plus trastuzumab, our trial was not designed to compare THP to T-DM1 plus pertuzumab directly,” DeMichele said. “However, the toxicity seen in the TDM-1 plus pertuzumab arm was clearly less than with paclitaxel plus trastuzumab or THP.”


  1. DeMichele AM, Moulder S, Buxton M, et al. Efficacy of T-DM1+pertuzumab over standard therapy for HER2+ breast cancer: results from the neoadjuvant I-SPY 2 TRIAL. Oral presentation at: AACR Annual Meeting 2016; April 16-20, 2016; New Orleans, LA.