T-DM1 vs TH for Breast Cancer

Recruiting at 58 trial locations

Overseen By Sara Tolaney, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Paclitaxel

Disqualifiers: Pregnancy, Liver disease, Prior chemotherapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 1 year

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two different treatments for breast cancer that tests positive for the HER2 protein. The goal is to determine how these combinations work after surgery to prevent cancer recurrence. Participants will receive either a combination of T-DM1 (Kadcyla, a type of targeted therapy) and Trastuzumab SC (Herceptin Hylecta) or Paclitaxel (a chemotherapy drug) with Trastuzumab SC, followed by Trastuzumab SC alone. This trial targets individuals newly diagnosed with HER2-positive breast cancer who have node-negative or micrometastatic cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot receive hormonal therapy during the first 12 weeks of the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found T-DM1 (Kadcyla) to be relatively safe and well-tolerated for treating HER2-positive breast cancer, though some participants experienced severe side effects requiring hospital care. This treatment is already approved for another type of breast cancer, indicating a level of safety.

Research has shown that Paclitaxel can cause serious side effects, such as low white blood cell counts (neutropenia), which can hinder the body's ability to fight infections. Some individuals may also have allergic reactions to the liquid used in Paclitaxel, so discussing any allergies with the trial team is crucial.

Trastuzumab SC (subcutaneous) is another component of the treatment. It is a form of Herceptin administered under the skin. Herceptin is widely used for HER2-positive breast cancer, and its safety is well-documented, though side effects can occur.

Prospective trial participants should consider these factors and discuss them with healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for breast cancer because they offer innovative approaches to tackling the disease. Unlike standard chemotherapy, trastuzumab-emtansine (T-DM1) combines an antibody with a chemotherapy drug, delivering the treatment directly to cancer cells, which could minimize damage to healthy cells. Additionally, trastuzumab is being administered subcutaneously (SC) rather than intravenously, potentially making the treatment more convenient and less time-consuming for patients. Meanwhile, the combination of paclitaxel with trastuzumab SC is noteworthy because it integrates a well-known chemotherapy agent with targeted therapy, aiming to enhance effectiveness while reducing side effects.

What evidence suggests that this trial's treatments could be effective for breast cancer?

This trial will compare two treatment approaches for HER2-positive breast cancer. Research has shown that trastuzumab-emtansine (T-DM1), which participants in Arm A of this trial may receive, is effective for treating HER2-positive breast cancer. One study found that T-DM1 reduced the chance of cancer recurrence by 50% compared to other treatments, meaning patients were less likely to experience a return of their cancer. Another study found that T-DM1 helped patients live longer without disease progression.

In Arm B of this trial, participants will receive a combination of paclitaxel with trastuzumab SC (under the skin). Evidence indicates that nab-paclitaxel, a similar drug, effectively treats breast cancer. It has been shown to help stop cancer from progressing and is generally well-tolerated by patients. These findings suggest both treatments have strong potential to manage HER2-positive breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Sara M. Tolaney, MD MPH

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with HER2-positive, Stage I breast cancer that's been surgically removed and has no lymph node involvement or only micrometastases. Participants must have good liver and bone marrow function, clear surgical margins, an ECOG status of 0 or 1, and a heart ejection fraction ≥50%. It excludes those with prior chemotherapy within 5 years, certain other cancers, active severe illnesses, pregnant/nursing women, or those not using contraception.

Inclusion Criteria

Patients must be able to sign informed consent

Patients must be willing to use contraception

Patients must be able to read and understand English for quality of life surveys

Exclusion Criteria

I have had breast cancer before.

Patients with intercurrent illnesses that may limit compliance with study requirements

I have an active liver condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either T-DM1 followed by Trastuzumab SC or Paclitaxel with Trastuzumab SC, followed by Trastuzumab SC alone

1 year

Every 3 weeks for T-DM1 and Trastuzumab SC; weekly for Paclitaxel

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Paclitaxel
• trastuzumab-emtansine
• Trastuzumab SC

Trial Overview The ATEMPT 2.0 study compares two post-surgery treatments for early-stage HER2-positive breast cancer: Trastuzumab-emtansine (T-DM1) versus a combination of Subcutaneous Trastuzumab (Herceptin Hylecta) and Paclitaxel. The goal is to see which therapy better prevents cancer recurrence.

How Is the Trial Designed?

Group I: Arm B: Paclitaxel with Trastuzumab SC, followed by Trastuzumab SC alone Experimental Treatment 2 Interventions

Randomized participants will receive weekly intravenous Paclitaxel for 12 weeks (4 cycles) and Trastuzumab SC (subcutaneous) every 3 weeks for 17 cycles. The first 4 doses Trastuzumab SC are given with Paclitaxel.

Group II: Arm A. T-DM1 followed by Trastuzumab SC Experimental Treatment 2 Interventions

Randomized participants will receive intravenous T-DM1 every 3 weeks for 6 cycles (18 weeks) and then Trastuzumab SC (subcutaneous) every 3 weeks for 11 cycles

Paclitaxel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

In a study of 35 HER2+ breast cancer patients receiving trastuzumab emtansine (T-DM1) with concurrent radiotherapy, a significant number experienced skin toxicity, with 22 patients reporting grade 2 or higher toxicity.

Three patients experienced grade 3 skin toxicities, highlighting the need for careful monitoring of skin reactions in patients undergoing this combined treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute skin radiation toxicity seen with concurrent T-DM1: A single institutional report of 35 patients. Dastgheyb, SS., Kim, K., Doucette, A., et al.[2023]

In the phase III KAITLIN study involving 1846 adults with high-risk HER2-positive early breast cancer, replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1) did not significantly improve invasive disease-free survival compared to the standard treatment of trastuzumab plus pertuzumab with chemotherapy.

While both treatment regimens showed favorable outcomes, the completion rate for the T-DM1 group was lower (65.0%) due to more laboratory abnormalities, indicating potential safety concerns despite similar rates of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. Krop, IE., Im, SA., Barrios, C., et al.[2023]

In a study of 93 older women (aged 65 and above) with advanced HER2-positive breast cancer treated with ado-trastuzumab emtansine (T-DM1), the median overall survival was 15.0 months, indicating that T-DM1 is an effective treatment option for this age group.

The treatment was generally well-tolerated, with 92.5% of patients experiencing adverse events, but only 30.1% having severe (grade 3 or 4) events, suggesting that while side effects are common, they are manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of trastuzumab emtansine in older patients with HER2-positive advanced breast cancer: a real-world study. Cil, I., Kucukarda, A., Atcı, MM., et al.[2022]

Ado-trastuzumab emtansine (T-DM1) is more cost-effective than trastuzumab for treating HER2+ early breast cancer, resulting in lower lifetime costs by approximately $40,271 while providing more life-years (2.980) and quality-adjusted life-years (2.336).

Patients receiving T-DM1 spend less time in expensive health states due to a lower overall recurrence rate, despite a higher likelihood of distant recurrence among those who do experience it, indicating improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness Analysis of Ado-trastuzumab Emtansine (T-DM1) for the Adjuvant Treatment of Patients With Residual Invasive HER2+ Early Breast Cancer in the United States. Sussell, J., Singh Jhuti, G., Antao, V., et al.[2023]

Trastuzumab emtansine (Kadcyla®) is effective in reducing the risk of invasive disease recurrence or death by 50% compared to trastuzumab in patients with HER2-positive early breast cancer after neoadjuvant treatment, as shown in the KATHERINE trial.

The safety profile of trastuzumab emtansine is consistent with previous findings, with more adverse events reported compared to trastuzumab, leading to its recommendation as a preferred treatment option in updated guidelines for high-risk breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Emtansine: A Review of Its Adjuvant Use in Residual Invasive HER2-Positive Early Breast Cancer. Lyseng-Williamson, KA.[2022]

In a study of 128 female patients with HER2-positive metastatic breast cancer who previously received trastuzumab emtansine (T-DM1), the median progression-free survival (rwPFS) was 5.7 months, indicating some effectiveness of post-T-DM1 therapies.

Patients who continued anti-HER2 therapy after T-DM1 had a better median rwPFS of 6.3 months compared to 4.8 months for those who did not, suggesting that ongoing anti-HER2 treatment may provide additional benefits, although overall effectiveness remains limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of post-trastuzumab emtansine treatment in patients with HER2-positive, unresectable and/or metastatic breast cancer: a retrospective observational study (KBCSG-TR 1917). Nakayama, T., Yoshinami, T., Yasojima, H., et al.[2023]

In a study of 22 patients with HER2-positive metastatic breast cancer, trastuzumab deruxtecan (T-DXd) showed a median progression-free survival of 9.7 months and an objective response rate of 61.9%, indicating its efficacy as a treatment option.

T-DXd was particularly effective in patients with heterogeneous or reduced HER2 expression, achieving partial responses in patients who did not respond to the previous treatment with ado-trastuzumab emtansine (T-DM1), highlighting its potential to overcome resistance in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impacts of clinicopathological factors on efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer. Nakajima, H., Harano, K., Nakai, T., et al.[2022]

Ado-trastuzumab emtansine (T-DM1) was approved in the U.S. for treating HER2 positive metastatic breast cancer based on the EMILIA phase III trial, which showed it was more effective than the standard treatment of lapatinib plus capecitabine.

Ongoing and planned trials are exploring T-DM1's use in various stages of breast cancer, and the review discusses its toxicity management and potential resistance mechanisms, highlighting its importance in current cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ado-trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: latest evidence and clinical potential. Peddi, PF., Hurvitz, SA.[2022]

In a study of 128 patients with advanced HER2+ breast cancer treated with ado-trastuzumab emtansine (T-DM1), the median progression-free survival was 8.7 months and overall survival was 20.4 months, indicating its efficacy in a real-world setting.

The safety profile of T-DM1 was consistent with existing literature, but the study noted higher rates of peripheral neuropathy (21.9%) and liver toxicity (19.5%), which are important considerations for its use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of T-DM1 in patients with advanced HER2-positive breast cancer The Royal Marsden experience. Battisti, NML., Rogerson, F., Lee, K., et al.[2021]

In the phase III EMILIA trial, trastuzumab emtansine (T-DM1) demonstrated a significantly better safety profile compared to capecitabine plus lapatinib (CAP + LAP) in treating HER2-positive metastatic breast cancer, leading to fewer severe treatment-related adverse events.

The management of adverse events resulted in lower costs for T-DM1 (CAD 3380) compared to CAP + LAP (CAD 6901), indicating that T-DM1 not only provides effective treatment but also offers substantial savings to the Canadian public health-care system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System. Piwko, C., Prady, C., Yunger, S., et al.[2019]

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that effectively targets HER2-positive breast cancer while minimizing off-target side effects, combining the benefits of targeted therapy with potent cytotoxic action.

T-DM1 has shown significant improvements in patient prognosis when used in neoadjuvant therapy and as a rescue treatment for advanced breast cancer, with ongoing clinical trials exploring its efficacy in other solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical research progress of T-DM1 in breast cancer]. Li, LX., Ma, F.[2021]

In a study of 119 patients with HER2-positive breast cancer, obese patients receiving ado-trastuzumab emtansine (T-DM1) experienced significantly more treatment modifications due to adverse events compared to non-obese patients (45% vs 25%).

Obese patients also had higher rates of treatment delays (36% vs 16%) and specific adverse events, such as decreased left ventricular ejection fraction and increased bilirubin levels, indicating a need for careful monitoring and potential adjustments in treatment for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of obesity on safety outcomes and treatment modifications with ado-trastuzumab emtansine in breast cancer patients. Lee, A., Larck, C., Moore, DC.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9016319/

A Real-World Efficacy of Nab-Paclitaxel Monotherapy in ... In conclusion, this real-world data shows that nab-paclitaxel is an effective treatment option in metastatic breast cancer. Nab-paclitaxel was well tolerated ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.19.00877

Nab-Paclitaxel: A New Standard of Care in Neoadjuvant ... Outcome Data for Trials of Nab-Paclitaxel in Metastatic Breast Cancer. A subsequent phase II trial in 302 patients with metastatic disease ...

3. clinical-breast-cancer.com clinical-breast-cancer.com/article/S1526-8209(18)30064-8/fulltext

Final Effectiveness and Safety Results of NABUCCO A total of 697 patients had evaluable data with a median follow-up of 17.7 months. Median time to progression was 5.9 months (95% confidence ...

4. nature.com nature.com/articles/s41598-019-57380-0

Efficacy and safety of nanoparticle-albumin-bound ... Nab-paclitaxel is an effective anti-tumor drug in the first-line treatment of MBC. Using nab-paclitaxel instead of sb-taxanes could ...

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-021-08441-z

A systematic review and meta-analysis of nab-paclitaxel ... Patients who received first-line nab-paclitaxel monotherapy showed a higher ORR (P = 0.006) and longer PFS (P = 0.045). Efficacy outcomes were ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/021660s047lbl.pdf

ABRAXANE (paclitaxel) Label - accessdata.fda.gov In clinical studies,. Grade 3-4 neutropenia occurred in 34% of patients with metastatic breast cancer (MBC), 47% of patients with non-small cell lung cancer ( ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3091407/

Safety and Efficacy of nab-Paclitaxel in the Treatment of ... The solvents used for dissolving hydrophobic molecules, paclitaxel and docetaxel are known to be associated with significant risk of hypersensitivity reactions ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3143911/

Nab-paclitaxel for the treatment of breast cancer This trial showed that nab-paclitaxel has superior clinical benefit including greater efficacy and a favorable safety profile without premedication compared ...

9. ema.europa.eu ema.europa.eu/en/documents/product-information/abraxane-epar-product-information_en.pdf

Abraxane, INN-paclitaxel - European Medicines Agency Clinical efficacy and safety. Breast cancer. Data from 106 patients accrued in two single-arm open-label studies and from 454 patients treated in a randomised ...

10. facingourrisk.org facingourrisk.org/XRAY/FDA-warns-against-tecentriq-and-paclitaxel-combo-therapy

FDA issues alert on a drug combination to treat triple ... Patients with advanced triple-negative breast cancer (TNBC) should avoid taking the therapy drug Tecentriq with paclitaxel.