Radiation and HER2-Targeted Therapy for Breast Cancer

(HERO Trial)

Recruiting at 434 trial locations

Overseen By Anna Shapiro

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This Phase III trial compares the recurrence-free interval (RFI) among patients with early-stage, low risk HER2+ breast cancer who undergo breast conserving surgery and receive HER2-directed therapy, and are randomized to not receive adjuvant breast radiotherapy versus those who are randomized to receive adjuvant radiotherapy per the standard of care.

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.

What data supports the effectiveness of the treatment for HER2-positive breast cancer?

Research shows that trastuzumab (Herceptin), a drug targeting the HER2 receptor, significantly improves survival rates in patients with HER2-positive breast cancer, reducing the risk of recurrence by about 50% and the risk of death by nearly 30% when used with chemotherapy. ^{1 2 3 4 5}

Is the combination of radiation and HER2-targeted therapy safe for humans?

The combination of radiation and HER2-targeted therapies like trastuzumab (Herceptin) appears to be generally safe, with no excess risk of toxicity reported. However, caution is advised when combining radiation with certain other drugs, as there is limited evidence on their safety. Trastuzumab has been shown to be safe in clinical trials, with the most significant side effect being cardiac issues in a small number of patients. ^{6 7 8 9 10}

How is the treatment of radiation and HER2-targeted therapy for breast cancer different from other treatments?

This treatment is unique because it combines radiation with trastuzumab (Herceptin), a drug that targets the HER2 protein, which is overexpressed in some breast cancers. Trastuzumab is known to enhance the effects of radiation, potentially making cancer cells more sensitive to it, but the best way to combine these therapies is still being studied. ^{7 8 11 12 13}

Research Team

Norman Wolmark, MD

Principal Investigator

NRG Oncology

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

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

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.

Participant Groups

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

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+

Findings from Research

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]

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]

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]

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]

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, 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]

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 (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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of HER2-positive breast cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

3. Germany pubmed.ncbi.nlm.nih.gov

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

4. Hungary pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Targeting HER2 in Advanced Breast Cancer. [2018]

6. United States 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. [2022]

7. France pubmed.ncbi.nlm.nih.gov

[Potential risk and benefit of the combination of trastuzumab to chemotherapy and radiation therapy in non-metastatic breast cancer]. [2015]

8. Poland pubmed.ncbi.nlm.nih.gov

Cardiotoxicity of concomitant radiotherapy and trastuzumab for early breast cancer. [2022]

9. Switzerland 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. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

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

11. United States pubmed.ncbi.nlm.nih.gov

Radiosensitization of chemotherapy-refractory, locally advanced or locally recurrent breast cancer with trastuzumab: a phase II trial. [2022]

12. England 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. [2020]

13. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab. [2016]