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T-DM1 Slows HER2-positive Metastatic Disease After Other Treatments Stop Working

New phase III trial results show time without disease worsening is longer for women given T-DM1 than those given doctor’s choice of treatment

October 21, 2013

Written By Nicole Katze, MA, Writer and Editorial Coordinator
Reviewed By Nicholas J. Robert, MD

Women with HER2-positive metastatic breast cancer who experience growth or worsening of the disease after treatment with other anti-HER2 therapies can expect a significant progression-free survival benefit from the recently-FDA approved anti-body drug conjugate T-DM1 (Kadcyla), first results from the phase III TH3RESA trial show. The findings were presented at the 2013 European Cancer Congress (ECC) in Amsterdam on September 28.

Anti-body drug conjugates are cancer medicines that pair chemotherapies with targeted therapies to deliver the chemotherapy to tumor cells more directly and lessen its harmful effects on healthy cells.

Background

The 2013 EMILIA study showed the medicine’s promise in effectively treating this subset of women by extending the length of overall survival, the time from the start of treatment to death from any cause, when compared to those treated with capecitabine (Xeloda) and lapatinib (Tykerb). EMILIA ultimately led to the FDA’s approval of T-DM1 for women with HER2-positive metastatic breast cancer, after standard anti-HER2 treatments stopped working.

TH3RESA further improved our understanding of the benefit offered by the medicine by comparing the survival benefit of treatment with T-DM1 to that of any standard-of-care therapy a woman’s doctor chose as treatment (physician’s choice) when the cancer grew or worsened after at least two other anti-HER2 medicines were tried.

Design

TH3RESA enrolled 606 people with metastatic HER2-positive breast cancer, in whom the cancer continued to grow or worsen after treatment with any two of the standard treatments: trastuzumab (Herceptin), taxane-based chemotherapy (Taxol, Taxotere), or lapatinib (Tykerb).

Participants were randomly assigned to one of two treatment groups:

  • 3.6mg/kg T-DM1 given by vein every 3 weeks or
  • Treatment of their physician’s choice

The primary endpoints of the study were progression-free survival (PFS), the time from the start of treatment until the disease grows or worsens or until death from any cause, and overall survival (OS), the time from the start of treatment until death from any cause.

This study was open label, which means that both the participant and the doctor knew which treatment was being given. Participants assigned to the physician’s choice group were allowed to change to the T-DM1 group if the cancer progressed during the trial.

Results

At ECC, the researchers presented data on PFS only. The investigators found that:

  • treatment with T-DM1 lowered the risk of cancer growing or spreading by 47 percent.
  • median PFS nearly doubled with T-DM1, from 3.3 months in the physician’s choice group to 6.2 months in the T-DM1 group.
  • 31.3 percent of participants in the T-DM1 group showed a response to the medicine, compared with 8.6 percent of participants in the physician’s choice group.
  • the T-DM1 group experienced 11.2 percent fewer occurrences of harmful side effects during treatment.

In the physician’s choice group, treatments were as follows:

  • 68.5 percent received chemotherapy plus trastuzumab
  • 16.8 percent received lapatinib plus trastuzumab
  • 10.3 percent received chemotherapy plus lapatinib
  • 1.6 percent received hormonal therapy (tamoxifen, aromatase inhibitors) plus trastuzumab

Trastuzumab, lapatinib, tamoxifen, aromatase inhibitors and chemotherapy agents are all standard treatments for breast cancer.

What This Means for You

The results from TH3RESA reaffirm the effectiveness of T-DM1 as a treatment for HER2-positive metastastic breast cancer. If you are a woman with this diagnosis, use of T-DM1 may mean you might enjoy longer progression-free survival with fewer side effects even after trastuzumab, the common first-line treatment for HER2-positive disease, stops working.

Though current research has focused on T-DM1 as a third-line treatment option—given only after two standard-of-care medicines failed to work—the ongoing MARIANNE trial is exploring T-DM1 alone versus T-DM1 plus pertuzumab (Perjeta) as a first-line treatment for HER2-positive metastatic breast cancer. TH3RESA will continue to collect data until overall survival findings are available.

Abstract no: LBA15,“T-DM1 for HER2-positive metastatic breast cancer (MBC): Primary results from TH3RESA, a phase 3 study of T-DM1 vs. treatment of physician's choice.” Breast cancer – advanced disease proffered papers session, 11.15 hrs CEST, Saturday 28 September, Hall 7.1.

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