Shorter HER2-targeted Therapy for Breast Cancer

Overseen By Danielle Allard, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Hospital Research Institute

Must be taking: HER2 targeted therapy

Disqualifiers: Metastatic disease, Residual invasive disease, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a shorter, 6-month course of trastuzumab (a HER2-targeted therapy) is effective and safe for individuals with early-stage HER2-positive breast cancer. The researchers aim to determine if those who have responded well to initial treatments can receive less therapy, potentially avoiding heart-related side effects and reducing costs. The trial seeks participants who have had early-stage HER2-positive breast cancer, received chemotherapy, and shown no signs of cancer in their breast or lymph nodes after surgery. As a Phase 4 trial, this research explores how this already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for trastuzumab?

Research has shown that trastuzumab is generally safe for individuals with early-stage, HER2-positive breast cancer. Studies have found that it significantly reduces the risk of cancer recurrence and lowers death rates. However, trastuzumab carries a risk of heart problems, such as heart failure, making regular check-ups crucial during treatment.

Trastuzumab is well-known among doctors and has been in use for many years. While it can be highly effective, patients should discuss any concerns with their healthcare provider. The provider can help determine if trastuzumab is the right choice based on individual health needs. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatment for early-stage HER2-positive breast cancer, which typically involves a longer course of trastuzumab combined with chemotherapy, this new approach focuses on a shorter, de-escalated HER2-targeted therapy. Researchers are excited because it aims to provide effective treatment while potentially reducing the side effects and overall treatment burden on patients. This approach targets patients who have shown a complete pathological response by the time of surgery, suggesting that a less intensive treatment might be just as effective for them. This could lead to a more personalized and less taxing treatment regimen for patients while maintaining high effectiveness.

What is the effectiveness track record for trastuzumab in treating early-stage, HER2-positive breast cancer?

Studies have shown that trastuzumab effectively treats HER2-positive early-stage breast cancer. When combined with chemotherapy, it can nearly halve the risk of cancer recurrence and reduce the chance of death by about a third. This trial will explore a de-escalated HER2-targeted treatment approach, shortening trastuzumab treatment for patients who achieve a pathological complete response at surgery. Research suggests that this shorter treatment might not impact survival rates. However, some patients may experience heart-related side effects, such as heart failure, though the benefits often outweigh these risks. Overall, trastuzumab has proven to be a powerful weapon against this type of breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Sharon McGee

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

This trial is for people with early-stage HER2-positive breast cancer who've had a complete response to initial chemo and HER2 therapy. They should not have any remaining invasive cancer after pre-surgery treatment, be able to consent in English or French, and haven't yet received 6 months of HER2 therapy.

Inclusion Criteria

I had successful breast cancer treatment with no cancer found after surgery and took HER2 therapy for less than 6 months.

My breast cancer is in stages I-III and may be ER/PR positive or negative, but is HER2 positive.

I can give verbal consent and fill out forms in English or French.

Exclusion Criteria

My cancer is still present after initial treatment or has spread.

Anything in your life that might make it hard for you to follow the trial rules.

I cannot receive more HER2-targeted therapy after my initial treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 months of HER2-targeted therapy after achieving a pathological complete response to neoadjuvant systemic therapy

6 months

Every 3 weeks

Follow-up

Participants are monitored for disease-free survival, overall survival, and cardiac events

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Trastuzumab

Trial Overview The study tests if 6 months of HER2-targeted therapy (Trastuzumab) is effective for patients who responded well to initial treatments. It's a single-arm, multicentre trial focused on those with non-metastatic breast cancer seeking less intensive post-surgery treatment.

How Is the Trial Designed?

Group I: De-escalated HER2 targeted treatment Experimental Treatment 1 Intervention

Patients with early-stage HER2-positive breast cancer who demonstrate a pathological complete response at time of surgery.

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Published Research Related to This Trial

The addition of trastuzumab (Herceptin®) to chemotherapy significantly improves overall survival in patients with HER2-positive early breast cancer, as shown by a systematic review of 31 studies published between 2008 and 2016.

The survival benefit of trastuzumab combined with chemotherapy has become more precise over time, reinforcing its status as the standard of care for HER2-positive early breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Herceptin® (trastuzumab) in HER2-positive early breast cancer: a systematic review and cumulative network meta-analysis. Wilson, FR., Coombes, ME., Brezden-Masley, C., et al.[2019]

Trastuzumab (Herceptin) is generally well-tolerated in cancer therapy, showing mild-to-moderate adverse effects primarily after the first dose, with a low incidence of severe side effects.

However, there is a significant risk of cardiac toxicity, particularly in patients who have previously received anthracycline chemotherapy, which was higher than expected and highlights the need for careful patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability in patients receiving trastuzumab with or without chemotherapy. Gianni, L.[2020]

Trastuzumab (Herceptin) is an effective treatment for metastatic breast cancer, especially when combined with paclitaxel, showing significant efficacy in a phase III study.

While trastuzumab is generally safe, it can cause infusion reactions and cardiotoxicity, particularly in patients with a history of high cumulative doses of anthracyclines, necessitating careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Trastuzumab (Herceptin)]. Tokuda, Y., Suzuki, Y., Saitou, Y., et al.[2015]

Trastuzumab significantly improves treatment outcomes for women with HER2 positive breast cancer, as shown in four large randomized trials.

The main safety concerns associated with trastuzumab are serious infusion-related reactions and cardiotoxicity, highlighting the need to weigh the benefits against these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab in the adjuvant treatment of breast cancer. Svetlovska, D., Mardiak, J., Kristova, V.[2016]

Adjuvant chemotherapy with trastuzumab for HER2 positive breast cancer significantly improves patient outcomes, providing an additional 0.84 quality-adjusted life years (QALY) and 1.16 life years gained (LYG) compared to chemotherapy without trastuzumab.

The cost-effectiveness analysis indicates that trastuzumab therapy has an incremental cost-effectiveness ratio (ICER) of approximately US$19,599.26 per QALY and US$14,180.68 per LYG, suggesting it may be considered cost-effective in Brazil under specific economic thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of trastuzumab for early breast cancer in Brazil. Botelho, CH., Estevez-Diz, MDP., Campolina, AG.[2022]

The Short-HER study is a large phase III trial involving 2500 patients with HER2-positive breast cancer, designed to compare the effectiveness of long-term (18 doses) versus short-term (9 doses) trastuzumab treatment after chemotherapy.

The primary goal of the study is to determine which treatment duration leads to better disease-free survival, helping to optimize adjuvant therapy for patients with HER2-overexpressing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicentric, randomized phase III trial of two different adjuvant chemotherapy regimens plus three versus twelve months of trastuzumab in patients with HER2- positive breast cancer (Short-HER Trial; NCT00629278). Guarneri, V., Frassoldati, A., Bruzzi, P., et al.[2018]

Trastuzumab (Herceptin) is a humanized monoclonal antibody that effectively targets the HER2/neu receptor, showing significant antitumor activity in patients with HER2/neu-amplified metastatic breast cancer based on multiple clinical trials.

When used in combination with chemotherapy, trastuzumab enhances treatment outcomes, improving time to progression, response rates, and overall survival, marking it as a pioneering example of targeted therapy in breast cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of treatment results with trastuzumab (Herceptin) in metastatic breast cancer. Hortobagyi, GN.[2016]

Trastuzumab (Herceptin) is highly effective in treating metastatic breast cancers that overexpress the HER-2/neu receptor, showing response rates comparable to traditional chemotherapy with significantly lower toxicity.

The success of trastuzumab in advanced cases has prompted ongoing clinical trials to explore its potential benefits in early-stage HER-2/neu-overexpressing breast cancer, indicating a shift towards more targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab: targeted therapy for the management of HER-2/neu-overexpressing metastatic breast cancer. Emens, LA.[2015]

Trastuzumab, while effective for treating HER2-positive breast cancer, can cause severe adverse effects such as significant edema, as demonstrated in a case of a 46-year-old woman who experienced extensive swelling after a single dose.

Treatment with methylprednisone was initiated to manage the edema, showing some mild reduction in symptoms, suggesting that early intervention may help mitigate this specific adverse reaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab treatment of invasive breast ductal carcinoma induces severe edema: a case report. Zhao, H., Zheng, J., Wang, Q., et al.[2022]

Trastuzumab (Herceptin) is effective in reducing relapse rates in patients with HER2+ breast cancer, which represents 20% to 25% of cases, but many patients either do not respond or develop resistance to the treatment.

The review highlights the basal molecular subtype as a potential predictor of increased risk and a contributing factor to drug resistance in HER2+ breast cancer, suggesting the need for alternative therapies to overcome this challenge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of anti-human epidermal growth factor receptor 2 therapies: predicting and overcoming herceptin resistance. Chung, A., Cui, X., Audeh, W., et al.[2021]

Herceptin (trastuzumab) is an effective treatment for metastatic breast cancer that overexpresses the HER2/Neu proto-oncogene, showing significant tumor regression and improved patient survival when used with chemotherapy.

As a single-agent therapy, Herceptin also provides a clear clinical benefit and is well tolerated, making it a strong first-line option for patients with HER2-amplified breast tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab, an appropriate first-line single-agent therapy for HER2-overexpressing metastatic breast cancer. Arteaga, CL.[2021]

Trastuzumab significantly improves survival rates in breast cancer patients with HER2 overexpression, but it is associated with an increased risk of cardiac toxicity, particularly in patients who have previously received anthracyclines.

The mechanism of trastuzumab-related cardiac toxicity is not fully understood, but it may sensitize heart cells to stress and injury, leading to myocardial dysfunction without causing visible structural damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab cardiotoxicity: biological hypotheses and clinical open issues. Bria, E., Cuppone, F., Milella, M., et al.[2019]

Trastuzumab (Herceptin) is a safe and effective treatment for patients with metastatic breast cancer that overexpresses the HER2 gene, showing response rates of 11% to 23% in various phase II studies involving heavily pretreated and previously untreated patients.

The treatment is associated with a low incidence of serious side effects, primarily cardiac dysfunction syndrome in less than 5% of patients, and does not cause common chemotherapy side effects like hair loss or low blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials of single-agent trastuzumab (Herceptin). Baselga, J.[2015]

Citations

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Escalating and de-escalating treatment in HER2-positive ... In a cohort study among breast cancer patients aged >65 and with full Medicare coverage, the rate of CHF was 29.4% among trastuzumab users as compared to 18.9% ...

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Outcomes of trastuzumab therapy in HER2-positive early ... Several randomized trials of trastuzumab (TZM) have demonstrated improved outcomes in patients with HER2-positive early breast cancer (EBC) [1–4]. We previously ...

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Trastuzumab for early-stage, HER2-positive breast cancer Pooled analysis of all trials found a highly significant reduction in recurrence (RR 0·66, 95% CI 0·62 to 0·71; p<0·0001; figure 1) and breast cancer mortality ...

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Trastuzumab Deruxtecan plus Pertuzumab for HER2 ... Trastuzumab deruxtecan plus pertuzumab led to a significantly lower risk of progression or death than THP when used as first-line treatment for ...

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Assessment of safety and tolerability of subcutaneous ... For many years, HER2-positive eBC was associated with higher risks of recurrence and mortality.

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Efficacy and safety of trastuzumab deruxtecan in HER2+ ... Our study supports the efficacy and safety of T-DXd in India in a real-world clinical setting with results being consistent across published literature.

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Patient-reported outcomes and hospitalization data in ... In the DESTINY-Breast03 clinical trial, trastuzumab deruxtecan (T-DXd) showed superior progression-free survival and overall survival versus trastuzumab ...