Data from the phase III TH3RESA clinical trial presented Dec. 11 at the San Antonio Breast Cancer Symposium showed that trastuzumab emtansine (T-DM1 [Kadcyla]) improved median overall survival for patients with HER2-positive, metastatic breast cancer that had progressed despite prior treatment with other HER2-targeted therapies, compared with those who received treatment of the physician’s choice.
After a median follow-up of 30.5 months, the median overall survival for patients assigned T-DM1 was 22.7 months, compared with 15.8 months for those assigned treatment of the physician’s choice.
What is T-DM1?
T-DM1 is an antibody-drug conjugate that has the monoclonal antibody trastuzumab (Herceptin) linked to the chemotherapy drug DM1, which is a maytansinoid. Trastuzumab by itself can stop the growth of cancer cells by binding to the HER2/neu receptor. The antibody locates cancer cells that overexpress HER2 and delivers the chemotherapy drug specifically to the tumor cell, thus potentially reducing the side effects typical of systemic delivery of toxic chemotherapy.
T-DM1 was approved by the U.S. Food and Drug Administration (FDA) in February 2013 for treating patients with HER2-positive, metastatic breast cancer that had progressed after treatment with trastuzumab and a taxane.
The National Comprehensive Cancer Network guidelines, which are widely used as the standard for cancer care, recommend using T-DM1 as a preferred treatment for patients with HER2-positive, metastatic breast cancer previously treated with trastuzumab. However, before this recommendation was made, many patients had received second- or later-line treatments, so TH3RESA was designed to test whether T-DM1 could benefit patients who had received several rounds of therapy, according to Hans Wildiers, MD, PhD, professor of medical oncology at KU Leuven in Belgium, who presented the study at the symposium.
One patient who, after enduring multiple rounds of treatments, is benefiting from T-DM1 for the past five years is Kim Alexander. “My decision to enroll on the T-DM1 clinical trial turned my life around almost immediately,” she said in an interview in 2013. Read her story here, and watch her video:
The TH3RESA Trial
The TH3RESA trial is a randomized, multicenter, two-arm, open-label study conducted in medical centers from 22 countries across Europe, North America, South America, and Asia-Pacific. The trial evaluated the efficacy and safety of T-DM1 in comparison with treatment of the physician’s choice for patients with metastatic or unresectable locally advanced/recurrent HER2-positive breast cancer that had progressed despite patients receiving at least two prior treatment regimens that included other HER2-targeted therapies, such as trastuzumab (Herceptin) and lapatinib (Tykerb).
Patients were randomized to receive either T-DM1 3.6 mg/kg intravenously every 21 days or treatment of the physician’s choice. All patients continued treatment until disease progression or unacceptable toxicity occurred.
The primary endpoints of the trial were progression-free survival (PFS) and overall survival (OS). Prior results from the TH3RESA trial on PFS analysis showed that T-DM1 almost doubled progression-free survival.
Wildiers, who presented the final OS results from the trial at the symposium, says, “Here we show that T-DM1 actually increased overall survival for heavily pretreated patients with HER2-positive, metastatic breast cancer. This is very important because several breast cancer therapies that increase progression-free survival do not in fact increase overall survival, and these patients urgently need new treatment options.”
T-DM1 less toxic than other therapies
The latest study results are particularly important because the overall survival benefit was seen in all subgroup analyses regardless of patient age, hormone-receptor status, visceral involvement, and number of prior treatment regimens. In addition, patients who received T-DM1 experienced fewer grade 3 or higher adverse events than those who received treatment of the physician’s choice.
“The fact that these patients lived longer with less toxicity suggests that T-DM1 is a good treatment option even for patients who have received two or more HER2-targeted treatment regimens,” says Wildiers.
Shiela Johnson-Glover, a stage IV HER2-positive breast cancer survivor from Illinois who benefited from T-DM1, says, “I thought the presentation was interesting because I could relate to this.”
Johnson-Glover, a member of the National Breast Cancer Coalition, tried multiple rounds of chemotherapy before she was treated with T-DM1 in March 2013, right after the drug was approved by the FDA in February of that year. “The tumor [in my breast] shrunk a great deal and the one in the liver shrunk by half,” she says. She has been off chemotherapy for more than two years now and continues to take Herceptin.
A volunteer on the Living Beyond Breast Cancer helpline, Johnson-Glover feels blessed that she has the opportunity to learn from experts and other advocates at the symposium.
Amanda Hynum, another breast cancer survivor and advocate from California, says the study results are reassuring. Hynum was diagnosed with stage II, HER2-positive invasive ductal carcinoma in 2013, when she was just 30, and was treated with a combination of taxotere, carboplatin and Herceptin.
“It is amazing that because of all advances in the field, HER2-positive breast cancer went from being a mystery disease to one that is treatable,” she says. “It makes me feel hopeful for the future.”
This post is adapted from an article on the website of Cancer Today, a quarterly magazine for cancer patients, survivors, and caregivers published by the AACR. Readall of Cancer Today’s SABCS coverage.
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