Radiation and HER2-Targeted Therapy for Breast Cancer

(HERO Trial)

Recruiting at 455 trial locations

Overseen By Anna Shapiro

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NRG Oncology

Must be taking: HER2-targeted therapy

Must not be taking: Estrogen replacement

Disqualifiers: Metastatic disease, Mastectomy, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks for initial therapy, followed by 9 months of trastuzumab monotherapy

1300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether skipping radiation after surgery is as effective as the standard treatment for individuals with early-stage HER2-positive breast cancer. It compares two groups: one receives the usual treatment of surgery, HER2-targeted therapy (such as Herceptin or Trastuzumab), and radiation, while the other skips radiation. The goal is to determine if those who skip radiation achieve similar outcomes to those who do not. Individuals who have undergone breast-conserving surgery and completed at least 12 weeks of chemotherapy with HER2-targeted therapy may be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does require that patients on estrogen replacement therapy stop before joining. It's best to discuss your specific medications with the trial team.

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

Research has shown that treatments targeting HER2, such as trastuzumab, are safe for early-stage, HER2-positive breast cancer. In previous studies, patients using trastuzumab experienced good outcomes, with a reduced risk of cancer recurrence.

Trastuzumab has already received FDA approval for this type of cancer, indicating it has passed rigorous safety tests. Most patients tolerate these treatments well, and side effects are usually manageable.

Evidence indicates that while some side effects can occur, they are generally not serious. This makes HER2-targeted therapies a safe option for many individuals with HER2-positive breast cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about exploring these treatment protocols for breast cancer because they offer a potential shift in managing HER2-positive cases. Traditionally, patients receive both HER2-targeted therapies and adjuvant breast radiation. However, one approach in this trial omits the radiation, focusing solely on systemic HER2-targeted therapy. This could mean fewer side effects and a more streamlined treatment process for patients, which is a significant advantage if it proves to be as effective as the current standard of care. By comparing these two approaches, researchers hope to determine if the omission of radiation can maintain treatment effectiveness while improving patients' quality of life.

What evidence suggests that this trial's treatments could be effective for early-stage, low risk HER2+ breast cancer?

Research has shown that HER2-targeted therapy, such as trastuzumab, significantly reduces the likelihood of breast cancer recurrence and decreases the risk of death from the disease. One study demonstrated that adding trastuzumab to chemotherapy reduced the recurrence rate and mortality risk by about a third for patients with early-stage, HER2-positive breast cancer. Another study found that patients who received trastuzumab had about a 97% chance of surviving without invasive breast cancer after five years, compared to 94% for those who did not receive it. In this trial, one group of participants will receive standard HER2-targeted therapy without adjuvant breast radiation, while another group will receive standard adjuvant breast radiation alongside their HER2-targeted therapy. These findings suggest that HER2-targeted therapy effectively treats HER2-positive breast cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

Norman Wolmark, MD

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for men and women aged 40 or older with early-stage, low-risk HER2-positive breast cancer who've had breast conserving surgery and at least 12 weeks of chemo with HER2-targeted therapy. They must have no metastatic disease, negative lymph nodes, and be HIV-positive on effective treatment if applicable. Pregnant or breastfeeding individuals are excluded.

Inclusion Criteria

I received at least 12 weeks of chemo and HER2 therapy before surgery.

My tumor is HER2-positive according to the latest guidelines.

My breast cancer diagnosis was confirmed through tissue examination.

Exclusion Criteria

I have an active collagen disease like lupus, scleroderma, or dermatomyositis with high CPK.

My surgery showed cancer at the edges or couldn't be checked, but I'm eligible if further surgery removed all cancer.

My breast cancer tumor was larger than 2 cm after surgery, or larger than 3 cm before surgery with suspicious lymph nodes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HER2-directed therapy, with some receiving adjuvant breast radiotherapy and others not, based on randomization

12 weeks for initial therapy, followed by 9 months of trastuzumab monotherapy

Follow-up

Participants are monitored for recurrence-free interval, local regional recurrence, overall survival, and other outcomes

10.5 years

Long-term Follow-up

Participants are monitored for ipsilateral breast recurrence and patient-reported outcomes

7 years for specific outcomes

What Are the Treatments Tested in This Trial?

Interventions

• Standard of Care Adjuvant Breast Radiation
• Standard of Care HER2-targeted Therapy Without Adjuvant Breast Radiation

Trial Overview The study compares the effectiveness of standard HER2-targeted therapy alone versus combining it with adjuvant breast radiation in preventing cancer recurrence after surgery. Participants will either receive additional radiotherapy per standard care or not, alongside their ongoing HER2-directed treatments.

How Is the Trial Designed?

Group I: Standard of Care Adjuvant Breast Radiation Active Control 1 Intervention

Patients continue to receive their current planned adjuvant breast radiation and systemic HER2-targeted therapies

Group II: Standard of Care HER2-targeted Therapy Without Adjuvant Breast Radiation Active Control 1 Intervention

Patients continue to receive their current systemic HER2-targeted therapy without breast adjuvant radiation

Standard of Care HER2-targeted Therapy Without Adjuvant Breast Radiation is already approved in United States, European Union for the following indications:

Approved in United States as Herceptin for:

• Early-stage HER2-positive breast cancer
• Metastatic HER2-positive breast cancer
• HER2-positive metastatic stomach or gastroesophageal junction cancer

Approved in European Union as Herceptin for:

• Early-stage HER2-positive breast cancer
• Metastatic HER2-positive breast cancer
• HER2-positive metastatic stomach or gastroesophageal junction cancer

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

Southwest Oncology Group

Collaborator

Trials

389

Recruited

260,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Alliance for Clinical Trials in Oncology

Collaborator

Trials

521

Recruited

224,000+

Eastern Cooperative Oncology Group

Collaborator

Trials

272

Recruited

153,000+

SWOG Cancer Research Network

Collaborator

Trials

403

Recruited

267,000+

Published Research Related to This Trial

In a study of 1,503 patients with early-stage HER-2-positive breast cancer, concurrent treatment with trastuzumab and radiotherapy did not lead to an increase in acute adverse events after surgery, indicating a favorable safety profile.

While there was a higher incidence of leukopenia in patients receiving trastuzumab compared to those who did not, the overall rates of cardiac events remained low and stable, suggesting that the combination treatment is safe in terms of cardiac health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG Phase III Trial N9831. Halyard, MY., Pisansky, TM., Dueck, AC., et al.[2022]

Trastuzumab (Herceptin) has significantly improved the prognosis for patients with HER2 positive breast cancer over the past decade, demonstrating efficacy in both metastatic and adjuvant treatment settings.

While trastuzumab is now a standard treatment for HER2 positive breast cancer, the optimal timing and combination with chemotherapy and radiation therapy remain unclear, particularly due to concerns about cardiac toxicity when used with anthracyclines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Potential risk and benefit of the combination of trastuzumab to chemotherapy and radiation therapy in non-metastatic breast cancer]. Belkacémi, Y., Laharie-Mineur, H., Gligorov, J., et al.[2015]

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]

Herceptin (trastuzumab) is an effective treatment for HER-2-positive breast cancer, showing significant improvement in disease-free survival when used for one year in adjuvant therapy, based on interim analysis from four international trials.

The drug has been approved for use in metastatic breast cancer since 1998 in the U.S. and 2000 in the EU, and recent studies suggest it may also be beneficial in neoadjuvant therapy for early-stage HER-2-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Herceptin therapy in breast cancer: new indication?]. Lebeau, A.[2015]

HER2-targeted therapies, including trastuzumab and newer agents like lapatinib and pertuzumab, have significantly improved survival rates for patients with HER2-positive breast cancer, transforming it from a poor prognosis to a more manageable condition.

Current research is exploring the effectiveness of HER2-targeted treatments without chemotherapy and assessing the benefits of these therapies earlier in the treatment process, indicating a shift towards more personalized and effective management strategies for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of HER2-positive breast cancer. Figueroa-Magalhães, MC., Jelovac, D., Connolly, R., et al.[2022]

HER2 is a critical marker in 20%-30% of breast tumors, indicating a poor prognosis and necessitating its role in treatment decisions, highlighting the need for improved HER2 testing to avoid false negatives.

Trastuzumab (Herceptin) has shown significant efficacy in treating HER2-positive metastatic breast cancer, both as a standalone treatment and in combination with chemotherapy, underscoring its importance in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proposed treatment guidelines for HER2-positive metastatic breast cancer in Europe. Piccart, MJ.[2020]

In a Phase II trial involving 19 patients with HER2-positive breast cancer, the combination of trastuzumab and radiotherapy was well tolerated, with manageable side effects and no cases of symptomatic cardiac dysfunction reported.

The treatment showed promising efficacy, with 43% of patients achieving a substantial pathologic response after surgery, significantly higher than a comparison group, and a median overall survival of 39 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitization of chemotherapy-refractory, locally advanced or locally recurrent breast cancer with trastuzumab: a phase II trial. Horton, JK., Halle, J., Ferraro, M., et al.[2022]

Trastuzumab (Herceptin) has been shown to significantly improve outcomes in HER-2-positive breast cancer, reducing the risk of recurrence by about 50% and the risk of death by nearly 30%, based on evidence from five large phase III adjuvant trials.

Herceptin is now approved for use in combination with chemotherapy for the adjuvant treatment of HER-2-positive breast cancer, marking a significant advancement in the management of this previously challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Trastuzumab (Herceptin) in the adjuvant treatment of HER-2-positive early breast cancer]. Láng, I., Hitre, E.[2015]

Trastuzumab (Herceptin) is an effective treatment for breast cancer that overexpresses the HER 2 protein, which occurs in about 20% of cases and is associated with more aggressive tumors.

Clinical trials have shown that trastuzumab works well both on its own and when combined with chemotherapy, and it has also been beneficial in early treatment settings (neoadjuvant and adjuvant therapy).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab. Smith, IE., Cross, SG.[2016]

Targeted anti-HER2 therapies have significantly improved disease control and survival rates in patients with metastatic HER2-positive breast cancer, which affects about 20% of breast cancer cases.

This review highlights the importance of these therapies as the standard of care for first-line treatment and discusses ongoing advancements aimed at addressing remaining challenges in treating this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting HER2 in Advanced Breast Cancer. Zhu, X., Joy, AA.[2018]

Combining anti-HER2 monoclonal antibodies like trastuzumab and pertuzumab with radiation therapy appears to be safe, showing no significant increase in toxicity based on the reviewed literature.

However, caution is advised when combining radiation with tyrosine kinase inhibitors (like lapatinib and tucatinib) and certain antibody-drug conjugates, as the safety of these combinations is not well established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence. Debbi, K., Grellier, N., Loganadane, G., et al.[2023]

Trastuzumab, when combined with chemotherapy, significantly improves survival rates for patients with early-stage HER2-positive breast cancer, but it can cause cardiotoxicity in a small number of patients.

Caution is advised when irradiating the left breast or thoracic wall in patients receiving trastuzumab, as the long-term effects of combining this therapy with radiotherapy are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiotoxicity of concomitant radiotherapy and trastuzumab for early breast cancer. Marinko, T., Dolenc, J., Bilban-Jakopin, C.[2022]

In a study of 175 patients with advanced HER2+ breast cancer, the time to progression (TTP) was similar for those receiving trastuzumab alone followed by chemotherapy and those receiving upfront combination therapy, indicating that both treatment strategies are equally effective.

Patients without visceral disease experienced a significantly longer TTP when starting with trastuzumab alone (21.8 months) compared to those who received upfront combination therapy (10.1 months), suggesting that chemotherapy can be safely deferred in certain patients to reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do all patients with advanced HER2 positive breast cancer need upfront-chemo when receiving trastuzumab? Randomized phase III trial SAKK 22/99. Pagani, O., Klingbiel, D., Ruhstaller, T., et al.[2020]

Citations

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Trastuzumab for early-stage, HER2-positive breast cancer Adding trastuzumab to chemotherapy for patients with early-stage, HER2-positive breast cancer reduces recurrence of and mortality from breast cancer by a third, ...

2. herceptin.com herceptin.com/hcp/adjuvant-breast-cancer/efficacy/clinical-results.html

Herceptin Clinical Trial Results Herceptin was studied as adjuvant treatment in 4 pivotal trials involving more than 10,000 people with HER2+ breast cancer.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5494230/

Outcomes of Trastuzumab Therapy for 6 and 12 Months in ... Trastuzumab therapy for 12 months reduced the recurrence rate in post-operative breast HER-2 positive cancer patients but did not significantly reduce ...

4. nature.com nature.com/articles/s41598-022-05209-8

Efficacy of adjuvant trastuzumab in women with HER2- ... Five-year invasive breast cancer-free survival was about 97% in patients who received adjuvant trastuzumab compared to 94% in the control group.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e13023

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.

6. sciencedirect.com sciencedirect.com/science/article/pii/S1526820923001088

Newly Approved and Emerging Agents in HER2-Positive ... However, final OS data indicated no statistically significant survival benefit to margetuximab versus trastuzumab, with mOS values of 21.6 months versus 21.8 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11178646/

Safety profile of trastuzumab deruxtecan in advanced breast ... The median progression-free survival (PFS) was 17.8 months (95% confidence interval [CI] 14.3–20.8) for patients who received T-DXd (n = 406) compared with 6.9 ...

8. biomarkerres.biomedcentral.com biomarkerres.biomedcentral.com/articles/10.1186/s40364-024-00565-1

HER2-targeted therapies in cancer: a systematic review Preliminary results from the CRISTINA SAURA study demonstrated that treatment with SYD985 was effective (ORR of 33% and mPFS of 9.4 months) in ...