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Can Treatment Regimens Before Surgery for Early-Stage HER2-Positive Breast Cancer Omit Chemotherapy?

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Treating early-stage HER2-positive breast cancer before surgery with the combination of chemotherapy, Herceptin (chemical name: trastuzumab), and Perjeta (chemical name: pertuzumab) seems to be more effective than the combination of Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine) and Perjeta before surgery, according to results from the KRISTINE study.

The results were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting on June 5, 2019, and published June 3, 2019, in the Journal of Clinical Oncology.

About Kadcyla

Kadcyla is a combination of Herceptin and the chemotherapy medicine emtansine. Emtansine, like some other chemotherapy medicines, disrupts the way cells grow. Emtansine isn’t a targeted medicine, so it can affect healthy cells as well as cancer cells.

Kadcyla was designed to deliver emtansine to cancer cells in a targeted way by attaching emtansine to the targeted therapy Herceptin. Herceptin then carries emtansine to the HER2-positive cancer cells.

Kadcyla is given intravenously, which means the medicine is delivered directly into your bloodstream through an IV or port. Kadcyla usually is given every 3 weeks in a doctor’s office.

Kadcyla is approved by the FDA to treat:

  • HER2-positive metastatic breast cancer that has previously been treated with Herceptin and taxane chemotherapy
  • HER2-positive early-stage breast cancer after surgery if there were cancer cells found during surgery (residual disease) after treatment with a taxane chemotherapy and Herceptin before surgery.

Doctors call treatments given after surgery adjuvant treatments. Doctors call treatments given before surgery neoadjuvant treatments.

About the KRISTINE study

The combination of chemotherapy, Herceptin, and Perjeta is the standard of care for neoadjuvant treatment of early-stage HER2-positive breast cancer. Still, because many of the side effects from this regimen are caused by the chemotherapy medicines, doctors have wondered if some people could skip chemotherapy and instead be treated with Kadcyla and Perjeta before surgery. The KRISTINE study was designed to test this idea.

One way doctors judge the effectiveness of neoadjuvant treatments is to look at the tissue removed during surgery to see if any actively growing cancer cells are present. If no active cancer cells are present, doctors call it a “pathologic complete response” or pCR. If there are cancer cells present in the tissue removed, this cancer is called “residual disease.”

The study randomly assigned 444 people diagnosed with early-stage HER2-positive breast cancer to one of two neoadjuvant treatment regimens:

  • 223 people were treated with Kadcyla and Perjeta (the experimental arm)
  • 221 people were treated with the chemotherapy medicines Taxotere (chemical name: docetaxel) and carboplatin, plus Herceptin and Perjeta (the standard of care arm)

About half the people in the study were younger than 50 and half were older; ages ranged from 22 to 79.

Other characteristics of the people in the study:

  • about 62% were diagnosed with HER2-positive breast cancer that also was hormone-receptor-positive
  • about 83% were initially diagnosed with stage IIA to IIIA breast cancer
  • about 17% were initially diagnosed with stage IIIB to IIIC breast cancer
  • about 66% were white, about 2% were Black, and about 25% were Asian

All the people in the study had surgery to remove the breast cancer 2 to 6 weeks after the last dose of neoadjuvant treatment.

Within 9 weeks of surgery, the people in the study resumed treatment with the anti-HER2 therapy that had been assigned — either Kadcyla and Perjeta or Herceptin and Perjeta — for 12 cycles.

If any participant in the Kadcyla and Perjeta arm did not have a pCR — meaning residual disease was found during breast cancer surgery — the person was encouraged to receive standard adjuvant chemotherapy before starting adjuvant Kadcyla and Perjeta.

KRISTINE results

After about 3 years of follow-up, the study results showed:

  • Event-free survival was better in the people treated with chemotherapy, Herceptin, and Perjeta compared to people treated with Kadcyla and Perjeta. The researchers defined event-free survival as the time from when the person was randomly assigned to a neoadjuvant treatment group until the cancer grew, including if the cancer grew before surgery.
  • Invasive disease-free survival was similar for the two treatment arms. The researchers defined invasive disease-free survival as the time from surgery until the cancer recurred, either in the same breast, the opposite breast, or someplace else in the body.
  • Overall, five people being treated with chemotherapy, Herceptin, and Perjeta died and six people being treated with Kadcyla and Perjeta died.
  • Rates of severe side effects were higher in the chemotherapy/Herceptin/Perjeta arm compared to the Kadcyla/Perjeta arm. Still, more people in the Kadcyla/Perjeta arm stopped treatment because of side effects compared to people in the chemotherapy/Herceptin/Perjeta arm.
  • People in the Kadcyla/Perjeta arm had better quality of life compared to people in the chemotherapy/Herceptin/Perjeta arm.

Because rates of invasive disease-free survival were similar between the two treatment groups, the researchers said this suggested that there may be some people who may be able to avoid neoadjuvant chemotherapy and instead be treated with Kadcyla and Perjeta.

“The clinical utility of chemotherapy-sparing HER2 neoadjuvant therapy needs to be confirmed in prospective studies, hopefully using biomarkers,” said lead author Sara Hurvitz, M.D., of the UCLA Jonsson Comprehensive Cancer Center. “Data from [the] KAITLIN [study] will further define the clinical utility of adjuvant T-DM1 plus pertuzumab in patients with HER2-positive early breast cancer.”

What this means for you

Unfortunately, the results from the KRISTINE study don’t give us a clear answer about which group of people diagnosed with early-stage HER2-positive breast cancer can avoid neoadjuvant chemotherapy and opt for treatment with Kadcyla and Perjeta instead. The study hints that there may be a subgroup of people who can avoid neoadjuvant chemotherapy, but the study was not designed to figure out who those people are.

So if you’ve been diagnosed with early-stage HER2-positive disease and will be having neoadjuvant treatment, you doctor will likely recommend the current standard of care, chemotherapy plus Herceptin and Perjeta.

Stay tuned to for results from the ongoing KAITLIN trial, which will, we hope, offer more refined information on the benefits of using Kadcyla before surgery for specific types of early-stage HER2-positive breast cancer.

Written by: Jamie DePolo, senior editor

Reviewed by: Brian Wojciechowski, M.D., medical adviser

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