The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

The final analysis of results of a phase 3 study comparing 2 different pertuzumab-containing regimens for the treatment of patients with HER2-positive, locally-advanced breast cancer delivered in both neoadjuvant and adjuvant settings showed a lower rate of locoregional progression before surgery for patients receiving a TCH-based (ie, docetaxel, carboplatin, and trastuzumab) regimen including pertuzumab compared with the combination of trastuzumab emtansine (T-DM1) and pertuzumab. The findings of this study were presented at the 2019 American Association of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

The combination of chemotherapy with trastuzumab and pertuzumab is the standard of care for patients with HER2-positive breast cancer receiving neoadjuvant therapy. Because many of the adverse effects of this treatment are associated with the chemotherapy components, use of trastuzumab emtansine (T-DM1) plus pertuzumab could potentially provide an efficacious, less toxic, alternative in this setting.

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In the open-label, randomized KRISTINE trial ( Identifier: NCT02131064) 444 patients with HER2-positive, locally advanced (tumor >2 cm) operable invasive breast cancer were randomly assigned in a 1:1 ratio to receive 6 cycles of neoadjuvant therapy with either T-DM1 plus pertuzumab followed by surgery and 12 cycles of adjuvant T-DM1 plus pertuzumab (223 individuals), or 6 cycles of TCH (docetaxel, carboplatin, trastuzumab) plus pertuzumab followed by surgery and 12 cycles of pertuzumab plus trastuzumab in the adjuvant setting (221 individuals). The study population was stratified by tumor hormone receptor status, disease stage, and geographical location.

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Results of the KRISTINE study with respect to the primary end point, the percentage of participants with pathological complete response (pCR) following neoadjuvant therapy, as well as treatment toxicity, have been previously reported and showed significantly higher rates of pCR (ie, 55.7% vs 44·4%; P =.0155), for patients in the T-DM1 plus pertuzumab arm, as well as higher rates of ≥grade 3 adverse events for patients receiving TCH plus pertuzumab.2 Patients who received neoadjuvant T-DM1 plus pertuzumab without achieving a pCR were encouraged to undergo chemotherapy prior to receiving adjuvant T-DM1 plus pertuzumab.2

In this final analysis of the KRISTINE trial performed at a median follow-up of 37 months, results of secondary study end points, including rates of 3-year event-free survival (EFS), 3-year invasive disease-free survival (IDFS), as well as patient safety, were reported.

“I’d like to point out the definition of EFS was time from randomization to disease progression including local progression prior to surgery whereas IDFS was the time from surgery to the first documented occurrence of a progression event,” stated Dr Sara Hurvitz, who presented the results of this study.

A key finding from this analysis was that patients in the TCH arm had a superior 3-year EFS rate (94.2%) compared with patients in the T-DM1 arm (85.3%; hazard ratio [HR], 2.61; 95% CI, 1.36–4.98).  

“You can see early separation of the EFS curves prior to surgery without much change after surgery,” Dr Hurvitz noted.

This difference in EFS was largely driven by the respective rates of locoregional progression before surgery for the chemotherapy-based arm (0%) and the T-DM1 plus pertuzumab arm (6.7%). An exploratory analysis of patients in the T-DM1 arm showed lower rates of HER2 gene and HER2 protein expression for those with locoregional progression versus not.   

Three-year IDFS rates with (97.5% vs 96.7%) and without (84.2% vs 89.4%) a pCR for those in the TCH-based and T-DM1­–based arms, respectively, were similar in the 2 treatment arms. .

While the grade 3 or higher adverse event rate for the overall study was higher for patients receiving TCH-based treatment (ie, 67.6% vs 31.8%), the rate of treatment discontinuation due to adverse events was lower in this arm compared with patients receiving T-DM1 plus pertuzumab (ie, 11.0% vs  20.2%). When focusing on the adjuvant period only, there was a higher rate of grade 3 or higher adverse events in the T-DM1 plus pertuzumab arm (24.5%) compared with the trastuzumab plus pertuzumab arm  (9.9%), although 50 patients in the T-DM1 arm received conventional cytotoxic therapy in the adjuvant setting.

Patients in the T-DM1 arm were more likely to experience grade 3 or higher peripheral neuropathy, whereas those receiving TCH-based therapy had more instances of grade 3 or higher of neutropenia, diarrhea, febrile neutropenia, and anemja.   

In her concluding comments, Dr Hurvitz stated that “the clinical utility of chemotherapy-sparing HER2 neoadjuvant therapy needs to be confirmed in prospective studies, hopefully using biomarkers.”

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.


  1. Hurvitz SA, Martin M, Jung KH, et al. Neoadjuvant trastuzumab (H), pertuzumab (P), and chemotherapy versus trastuzumab emtansine (T-DM1) and P in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC): Final outcome results from the phase III KRISTINE study. Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, Illinois. Abstract 500.
  2. Hurvitz SAMartin MSymmans WF, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018;19(1):115-126.