T-DM1 Approval Expanded for HER2-Positive Breast Cancer (2024)

, by NCI Staff

T-DM1 Approval Expanded for HER2-Positive Breast Cancer (1)

The Food and Drug Administration (FDA) has expanded the approved use of the drug ado-trastuzumab emtansine (Kadcyla) to treat some women with HER2-positive breast cancer.

Ado-trastuzumab, also called T-DM1, was initially approved by FDA more than 6 years ago to treat women with metastatic HER2-positive breast cancer. Under the expanded approval, it can now be used when the cancer is far less advanced: as a post-surgical, or adjuvant, treatment in women with early-stage HER2-positive breast cancer. However, to be eligible to receive the drug under this newly approved use, women must first have undergone presurgical, or neoadjuvant, therapy to shrink their tumors and still have some signs of remaining invasive cancer, called residual cancer, in the breast or nearby lymph nodes.

The new approval, announced on May 3, is based on findings from a large clinical trial called KATHERINE that compared T-DM1 with trastuzumab (Herceptin) as an adjuvant treatment. In the trial, women treated with T-DM1 had a 50% reduced risk of their cancer returning or death than women treated with trastuzumab.

Side effects, including serious side effects, were more frequent in women treated with T-DM1. As a result, more women taking T-DM1 (29%) did not complete the full course of the adjuvant treatment than women taking trastuzumab (19%).

But many of these women did not have to stop taking the drug until they were near the end of their adjuvant treatment period, explained the study’s lead investigator, Charles Geyer, Jr., M.D., of the Virginia Commonwealth University Massey Cancer Center. In general, Dr. Geyer said, “the majority of women tolerated the drug reasonably well.”

The trial results, and the subsequent FDA approval, have already had an important impact on patient care, Dr. Geyer said.

“T-DM1 has now become the standard of care for women with HER2-positive breast cancer and residual invasive cancer following neoadjuvant therapy,” he said.

Building on Earlier Advances

Trastuzumab, a monoclonal antibody, was among the first FDA-approved targeted cancer therapies and has long been an established therapy for HER2-positive breast cancer. Trastuzumab latches on to HER2 proteins on the surface of breast cancer cells and prevents HER2 from stimulating cancer cell growth.

Known as an antibody–drug conjugate, T-DM1 chemically links the trastuzumab antibody to the chemotherapy drug emtansine (also known as DM1).

The antibody portion of T-DM1, in addition to blocking the activity of the HER2 protein on cancer cells, serves as a homing device for emtansine. Once the antibody binds to HER2 on cancer cells, emtansine is released into the cells.

After showing that T-DM1 improved how long women with metastatic HER2-positive breast cancer live, researchers quickly moved to test the drug in women with early-stage disease. The KATHERINE trial—funded by the manufacturer of T-DM1, Genentech—enrolled nearly 1,500 women with early-stage HER2-positive breast cancer, meaning their cancer was confined to the breast and the axillary lymph nodes. All women in the trial had evidence of residual disease after neoadjuvant therapy, which included chemotherapy and trastuzumab. Roughly 20% of the women also received pertuzumab (Perjeta) as part of their neoadjuvant therapy.

The goal of neoadjuvant therapy is to eliminate as much cancer as possible prior to surgery, and many women with early-stage HER2-positive breast cancer now receive neoadjuvant therapy, explained Janice Lyons, M.D., a radiation oncologist at the Case Comprehensive Cancer Center in Cleveland, who specializes in treating breast cancer. Some women with very small cancers, however, may proceed straight to surgery, she said.

For many women, neoadjuvant chemotherapy will eliminate all evidence of residual disease, Dr. Geyer said. Studies have consistently shown that women with early-stage breast cancerparticularly those with triple-negative or HER2-positive diseasewho don’t have residual disease after neoadjuvant chemotherapy live longer without their disease recurring, compared with women who have residual invasive cancer.

Adjuvant therapy with trastuzumab has been a standard treatment for women with HER2-positive breast cancer, regardless of whether they have residual disease.

Participants in the KATHERINE trial were randomly assigned to receive adjuvant therapy with either T-DM1 or trastuzumab (in 3-week treatment cyclesfor up to 14 cycles).

The researchers who led the trial estimated that, at 3 years after beginning adjuvant treatment, 88% of women treated with T-DM1 were alive and free of invasive cancer, compared with 77% of women treated with trastuzumab.

It will take longer follow-up to determine whether T-DM1 will ultimately improve how long patients live overall, Dr. Geyer stressed.

“These results are impressive and clinically meaningful,” wrote Daniel F. Hayes, M.D., a breast cancer expert at the University of Michigan Rogel Cancer Center, in an editorialthat accompanied the publication of the KATHERINE trial results last December in the New England Journal of Medicine. “Post-operative treatment with T-DM1 offers a major opportunity to improve long-term outcomes.”

Dr. Lyons agreed that adjuvant treatment with T-DM1 is the new standard of care for women with early-stage HER2-positive breast cancer who have residual invasive cancer after neoadjuvant chemotherapy. The “surprising result” from the KATHERINE trial, she said, is that all women benefited from T-DM1, “even those with very limited residual disease.”

Impact of Treatment Side Effects?

But these improvements, Dr. Hayes continued, do not come “without a price,” noting the higher rates of side effects and serious side effects. The latter included substantial drops in platelet levels and peripheral neuropathy.

Overall, 18% of women in the T-DM1 group stopped taking the drug because of specific side effects, compared with 2% of women in the trastuzumab group.

The increased side effects in women treated with T-DM1, Dr. Geyer noted, was most likely a cumulative effect of the pre- and post-surgical treatments. “Emtansine is a chemotherapy drug, and it was expected to add toxicity relative to no chemotherapy,” he said.

For some, lowering the dose of the drug alleviated side effects. Among the trial participants who eventually stopped taking T-DM1, some switched to trastuzumab for the remainder of the 14 cycles, which was a planned part of the study.

Dr. Lyons also noted that, in the KATHERINE trial, there was a slightly higher risk of lung inflammation (pneumonitis) in women who received T-DM1, although rates were low overall. This side effect was likely linked to radiation treatments those patients received. She advised clinicians to “carefully manage” the dose for any radiation treatment patients receive as part of adjuvant therapy with T-DM1.

Dr. Hayes advised against using T-DM1 in women without residual disease after neoadjuvant therapy or women with stage I disease at diagnosis. These patients “have a very favorable outcome” with the standard adjuvant therapy of paclitaxel and trastuzumab, he said.

T-DM1 Approval Expanded for HER2-Positive Breast Cancer (2024)

FAQs

T-DM1 Approval Expanded for HER2-Positive Breast Cancer? ›

The authors wrote in the background that T-DM1 is currently approved for the adjuvant treatment of patients with HER2-positive breast cancer with residual invasive disease after neoadjuvant treatment or with metastatic disease, and in the metastatic setting, it has shown similar efficacy with lower toxicity compared ...

What is the most appropriate cancer treatment for HER2-positive breast cancer? ›

Pertuzumab (Perjeta) treats HER2-positive early breast cancer, usually in combination with trastuzumab and chemotherapy. It's FDA-approved for neoadjuvant and adjuvant treatment. Neoadjuvant use: For people with HER2+ breast cancer that is locally advanced, inflammatory, or early-stage.

What is the new drug for HER2-positive breast cancer? ›

With FDA's expanded approval of trastuzumab deruxtecan (Enhertu), the HER2-targeted drug can now be used to treat people with many types of cancer. The drug trastuzumab deruxtecan (Enhertu) can now be used to treat a wide variety of cancers, thanks to a new approval from the Food and Drug Administration (FDA).

Is trastuzumab DM1 highly effective in preclinical models of HER2-positive gastric cancer? ›

T-DM1 showed a promising anti-tumor effect in HER2-positive gastric cancer cell lines in vitro and in vivo, even in tumors which had developed resistance to trastuzumab. T-DM1 therapy may warrant clinical trials for HER2-positive gastric cancer patients.

Is T-DM1 approved for breast cancer? ›

In February 2013, ado-trastuzumab emtansine (T-DM1, Kadcyla®) received regulatory approval in the United States for treatment-refractory human epidermal growth factor receptor 2 (HER2) positive metastatic or locally advanced breast cancer based on results from EMILIA, a large phase III trial that compared standard of ...

What is the life expectancy of someone with HER2-positive breast cancer? ›

According to the National Cancer Institute , HER2-positive breast cancer that has not spread to any other organs in the body or the axillary lymph nodes has a 5-year relative survival rate of 98.8% if it is HR-positive and 97.3% if it is HR-negative.

What is the gold standard treatment for HER2 breast cancer? ›

Based on the results of the NeoSphere and TRYPHAENA clinical trials, panel members concluded that the administration of dual HER2 receptor blockade trastuzumab + pertuzumab with chemotherapy in NAT is the optimal treatment option, especially in patients at high risk of disease recurrence.

What is the new cancer breakthrough in 2024? ›

The FDA granted accelerated approval to T-Dxd on April 5, 2024, for the treatment of patients with inoperable or metastatic tumors that express HER2 who have received prior systemic treatment and have no satisfactory alternative treatment options.

What is the breakthrough of HER2-positive breast cancer? ›

Now, depending on the stage of the cancer at diagnosis, women with HER2-positive breast cancer have among the highest survival rates of all women with breast cancer. That is thanks to the revolutionary breast cancer drug Herceptin, which was developed by a team of scientists led by oncologist Dennis J.

What is the chemo cocktail for HER2-positive breast cancer? ›

Ado-trastuzumab emtansine consists of the HER2-targeted antibody drug trastuzumab (Herceptin) and a chemotherapy called DM1 (so it's sometimes called T-DM1). The combination of drugs allows the targeted delivery of chemotherapy to HER2-positive cancer cells.

Is T-DM1 effective? ›

T-DM1 is an antibody drug conjugate that combines trastuzumab with emtansine via a stable thioether linker. In two phase III clinical trials, EMILIA and TH3RESA, T-DM1 was shown to be effective in HER2-positive metastatic breast cancer patients who had progressed to taxanes and trastuzumab.

What is the prognosis for trastuzumab? ›

In the trial, people with metastatic breast cancer who were treated with the HER2-targeted drug trastuzumab deruxtecan (Enhertu) lived nearly twice as long without their cancer growing, and lived 6 months longer overall, than those treated with standard chemotherapy.

What are the two ways in which Herceptin works to fight cancer? ›

Herceptin “targets” HER2 receptors to fight tumor cell growth. Studies have shown that Herceptin attaches to HER2 receptors. Herceptin may stop a HER2 receptor from telling the cell to grow and divide. Also, Herceptin may signal the body's immune system to destroy that cancer cell.

Do you lose your hair with T-DM1? ›

Can ado-trastuzumab emtansine (T-DM1), the active ingredient in Kadcyla, cause hair loss? It's not likely. Hair loss wasn't reported by people receiving Kadcyla in studies. Hair loss is a common side effect of some other breast cancer treatments.

How many cycles of T-DM1? ›

Patients received T-DM1 at a dose of 3.6 mg per kilogram of body weight or trastuzumab at a dose of 6 mg per kilogram intravenously every 3 weeks for 14 cycles. A loading dose of 8 mg of trastuzumab per kilogram was administered if more than 6 weeks had elapsed since the preceding dose of trastuzumab.

What is the response rate for T-DM1? ›

The T-DM1 arm also showed a higher response rate (43.6% vs. 30.8%; p < 0.001) and fewer grade 3–4 adverse events (41% vs 57%)6,7. Based on the results of the EMILIA trial, in February 2013, T-DM1 was approved by the US Food & Drug Administration (FDA) for the second-line treatment of HER2-positive breast cancer13.

What is the first-line treatment for HER2-positive breast cancer? ›

Exciting Data in the Treatment of HER2-low from SABCS 2023. Manali Bhave begins by discussing first-line therapy for HER2-positive metastatic breast cancer, which is typically taxane chemotherapy (like docetaxel or paclitaxel) plus trastuzumab and pertuzumab.

Does HER2-positive need chemo or surgery first? ›

Many women with HER2-positive cancers will be treated first with trastuzumab (with or without pertuzumab) followed by surgery and then more trastuzumab (with or without pertuzumab) for up to a year.

Is mastectomy necessary for HER2-positive breast cancer? ›

Golshan thinks one reason why people with HER2-positive breast cancer may choose mastectomy more often than BCS is because they often have more extensive disease. But many doctors usually treat the tumor with drug therapy before surgery, Golshan says.

What is the second line treatment for HER2-positive metastatic breast cancer? ›

Standard-of-care for HER2-positive metastatic breast cancer (HER2 + mBC) patients consists of trastuzumab ± pertuzumab with chemotherapy in first-line (1L), and ado-trastuzumab emtansine (T-DM1) or the more recently approved trastuzumab deruxtecan (T-DXd) in second-line (2L).

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