Radiation and HER2-Targeted Therapy for Breast Cancer
(HERO Trial)
Recruiting in Palo Alto (17 mi)
+429 other locations
Overseen byNorman Wolmark, MD
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.
12345Is 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.
678910How 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.
78111213Eligibility 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.
+15 more
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.
+17 more
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
Participant Groups
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.
2Treatment groups
Active Control
Group I: Standard of Care Adjuvant Breast RadiationActive Control1 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 RadiationActive Control1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Kaiser Permanente DublinDublin, CA
Los Angeles General Medical CenterLos Angeles, CA
University of California Davis Comprehensive Cancer CenterSacramento, CA
Loyola University Medical CenterMaywood, IL
More Trial Locations
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Who Is Running the Clinical Trial?
NRG OncologyLead Sponsor
Southwest Oncology GroupCollaborator
National Cancer Institute (NCI)Collaborator
Alliance for Clinical Trials in OncologyCollaborator
Eastern Cooperative Oncology GroupCollaborator
SWOG Cancer Research NetworkCollaborator
References
Treatment of HER2-positive breast cancer. [2022]The human epidermal growth factor receptor 2 gene (HER2) is overexpressed and/or amplified in ~15% of breast cancer patients and was identified a quarter century ago as a marker of poor prognosis. By 1998, antibody therapy targeting the HER2 pathway was shown to demonstrably improve progression-free and overall survival in metastatic disease, and in 2005 evidence of improvement in disease-free and overall survival from the first generation of trastuzumab adjuvant trials became available. However, not all patients with HER2 overexpression benefit from trastuzumab. Second-generation studies in metastatic disease led to the approval of several new HER2-targeted therapies using small molecule tyrosine kinase inhibitors such as lapatinib, new HER2/HER3 antibodies such as pertuzumab, and the new antibody chemotherapy conjugate ado-trastuzumab emtansine. These successes supported the launch of second-generation adjuvant trials testing single and dual HER2-targeted agents, administered concomitantly or sequentially with chemotherapy that will soon complete accrual. HER2-positive breast cancer in the setting of HER2-targeted therapy is no longer associated with poor prognosis, and recent guidance by the US Food and Drug Administration suggests that pathologic response to HER2-targeted therapy given preoperatively may allow an earlier assessment of their clinical benefit in the adjuvant setting. An adjuvant trial of trastuzumab in patient whose tumors express normal levels of HER2 and trials of single/dual HER2-targeting without chemotherapy are also ongoing. In this article, we review the current data on the therapeutic management of HER2-positive breast cancer.
Proposed treatment guidelines for HER2-positive metastatic breast cancer in Europe. [2020]The human epidermal growth factor receptor-2 (HER2) is overexpressed/amplified in 20%-30% of human breast tumors and is a marker for a poor prognosis. For these reasons, HER2 has been selected as a therapeutic target for breast cancer treatment. Oncologists can no longer ignore the importance of HER2 status for treatment algorithms in breast cancer. In light of the consequences of HER2 status on treatment selection, further research is warranted to refine and standardize HER2 testing in order to minimize false-negative results and optimize selection of treatment pathways. The anti-HER2 monoclonal antibody (MAb) trastuzumab (Herceptin) has proven valuable in treating HER2-positive, advanced-disease patients. and the availability of this novel biologic agent has important implications for clinical practice. This review describes a set of guidelines based on the current options for treatment of breast cancer. Two important factors have been taken into account in compiling these recommendations: (1) the lack of level I evidence to convincingly demonstrate the value of HER2 as a predictive marker for resistance or sensitivity to chemo- and hormonal therapy, and (2) the recently published pivotal phase II and III trial data proving the efficacy of trastuzumab as a single agent and in combination with chemotherapy in HER2-positive metastatic breast cancer.
[Herceptin therapy in breast cancer: new indication?]. [2015]HER-2 belongs to a family of four transmembrane receptor tyrosine kinases that mediate growth, differentiation and survival of cells. HER-2 overexpression and amplification occurs in approximately 15 to 25 % of breast cancers and is associated with aggressive tumour behaviour. Herceptin (trastuzumab), a humanized monoclonal antibody directed against the extracellular domain of the HER-2 receptor, has been shown to have clinical activity in HER-2-positive advanced breast cancer when administered alone or in combination with chemotherapy. It has been approved for HER-2-positive metastatic breast cancer by the United States Food and Drug Administration in 1998 and in the countries of the European Union in 2000. Recently, promising results of the four randomized international multicenter trials evaluating the therapeutic benefit of Herceptin in the adjuvant treatment of HER-2-positive primary breast cancer have been reported. Data of the first planned interim analysis of the studies showed significantly improved disease-free survival in patients assigned to one year of Herceptin compared to the control groups even after short term follow up. These results caused an immediate wave of demand for Herceptin in adjuvant therapy. Results of these studies are critically reviewed. Furthermore, the available preliminary results from studies using Herceptin in the primary (neoadjuvant) therapy of HER-2-positive breast cancer are addressed and possible implications for HER-2 testing are discussed.
[Trastuzumab (Herceptin) in the adjuvant treatment of HER-2-positive early breast cancer]. [2015]The prognosis of HER-2-positive breast cancer (characterized by amplification of the HER-2 oncogene and/or overexpression of HER-2 receptor) is unfavourable. Trastuzumab (Herceptin), a monoclonal antibody against HER-2 receptor can improve the outcome of HER-2-positive breast cancer. Up to now this was proven only in advanced disease. Recently five large multicentric phase III adjuvant trials gave level one evidence on the benefit of adjuvant treatment with Herceptin, concerning disease-free survival (DFS) and overall survival (OS). Herceptin has decreased the relative risk of recurrence with about 50% and that of death with nearly 30% in HER-2-positive early breast cancer. Based on these results Herceptin, together with chemotherapy, has been recently approved for the adjuvant treatment of HER-2-positive breast cancer.
Targeting HER2 in Advanced Breast Cancer. [2018]Human epidermal growth factor receptor 2 (HER2) is a human oncogene that is amplified in approximately 20% of breast cancers, and portends a worse prognosis if not treated with anti-HER2 agents. The advent of targeted anti-HER2 therapies has dramatically improved disease control and survival in patients with metastatic HER2-positive breast cancer, and is now considered standard of care in the first-line setting and beyond. This review summarizes the currently available data on targeted anti-HER2 therapies from completed randomized phase III clinical trials, and briefly discusses emerging advances that will address unmet needs in metastatic HER2-positive breast cancer.
Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG Phase III Trial N9831. [2022]To assess whether trastuzumab (H) with radiotherapy (RT) increases adverse events (AEs) after breast-conserving surgery or mastectomy.
[Potential risk and benefit of the combination of trastuzumab to chemotherapy and radiation therapy in non-metastatic breast cancer]. [2015]Trastuzumab (Herceptin) is the first humanised monoclonal antibody targeting the HER2 antigen in breast cancer. HER2 receptor has been individualised 20 years ago. During the past 10 years, trastuzumab administration has radically modified the prognosis of the patients that are treated for HER2 positive breast cancer. Its efficacy has been demonstrated in the metastatic and adjuvant settings. While, trastuzumab based-regimens became the standard of care in the treatment of HER2/neu positive breast cancer, the optimal combination (concurrently or sequentially) to chemotherapy and radiation therapy is still unknown. Indeed, while the concurrent administration of trastuzumab and anthracyclines is not recommended because of a high risk of cardiac toxicity, there is no published data on the best sequence of trastuzumab and radiation therapy administration, particularly when internal mammary chain is involved. The benefit/risk ratio of the concurrent and sequential administration of trastuzumab with chemotherapy and radiation therapy will be discussed in this review.
Cardiotoxicity of concomitant radiotherapy and trastuzumab for early breast cancer. [2022]Trastuzumab therapy given in combination with one of several chemotherapy regimens is currently considered the standard of care for the treatment of early-stage, human epidermal growth factor receptor-2 (HER2) -positive breast cancer. The treatment with trastuzumab is due to a significant impact on the survival part of the standard adjuvant treatment of patients with HER2-positive breast cancer. Patients treated with postoperative breast or chest wall irradiation receive trastuzumab concomitant with radiotherapy. In a small proportion of patients trastuzumab causes cardiotoxicity. Preclinical findings indicate a radiosensibilizing effect of trastuzumab in breast cancer cells, but it is not yet clear whether it radiosensibilizes cells of healthy tissues too.
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]Purpose: Over the past twenty years, anti-HER2 targeted therapies have proven to be a revolution in the management of human epidermal growth receptor 2 (HER2)-positive breast cancers. Anti-HER2 therapies administered alone or in combination with chemotherapy have been specifically studied. Unfortunately, the safety of anti-HER2 therapies in combination with radiation remains largely unknown. Thus, we propose a literature review of the risks and safety of combining radiotherapy with anti-HER2 therapies. We will focus on the benefit/risk rationale and try to understand the risk of toxicity in early-stage and advanced breast cancer. Methods: Research was carried out on the following databases: PubMed, EMBASE, ClinicalTrial.gov, Medline, and Web of Science for the terms "radiotherapy", "radiation therapy", "radiosurgery", "local ablative therapy", and "stereotactic", combined with "trastuzumab", "pertuzumab", "trastuzumab emtansine", "TDM-1", "T-Dxd", "trastuzumab deruxtecan", "tucatinib", "lapatinib", "immune checkpoint inhibitors", "atezolizumab", "pembrolizumab", "nivolumab", "E75 vaccine", "interferon", "anti-IL-2", "anti-IL 12", and "ADC". Results: Association of radiation and monoclonal antibodies such as trastuzumab and pertuzumab (with limited data) seems to be safe, with no excess risk of toxicity. Preliminary data with radiation and of antibody-drug conjugate of trastuzumab combined cytotoxic (trastuzumab emtansine, trastuzumab deruxtecan), given the underlying mechanism of action, suggest that one must be particularly cautious with the association. The safety of the combination of a tyrosine kinase inhibitor (lapatinib, tucatinib) and radiation remains under-studied. The available evidence suggests that checkpoint inhibitors can be safely administrated with radiation. Conclusions: HER2-targeting monoclonal antibodies and checkpoint inhibitors can be combined with radiation, apparently with no excess toxicities. Caution is required when associating radiation with TKI and antibody drugs, considering the limited evidence.
Clinical trials of single-agent trastuzumab (Herceptin). [2015]The HER2 gene (also known as neu and as c-erb-B2) encodes a 185-kd transmembrane glycoprotein receptor with intrinsic tyrosine kinase activity. HER2 is overexpressed in 25% to 30% of human breast cancers, plays a role in the pathogenesis of breast cancer, and predicts for a worse prognosis in patients with metastatic disease. Trastuzumab (Herceptin; Genentech, Inc, So. San Francisco, CA), a humanized monoclonal antibody that targets the HER2 oncogene receptor, was shown to be active in preclinical models. In initial phase I clinical trials, trastuzumab was found to be safe and to exhibit dose-dependent pharmacokinetics. Three phase II studies of single-agent trastuzumab, which was administered weekly in the outpatient setting, have now been conducted in patients with HER2-overexpressing metastatic breast cancer. In the initial phase II study, the response rate was 11% in a heavily pretreated patient population. In a pivotal follow-up study of single-agent trastuzumab, more than 200 patients who had received at least one prior chemotherapeutic regimen for metastatic disease were entered. Despite a number of unfavorable baseline characteristics, the response rate reported by an independent response evaluation committee was 15%. A more recent study in previously untreated patients has shown a 23% response rate. The median duration of response in these trials has ranged from 6.6 to 9.1 months. In these three phase II studies, trastuzumab has been shown to be safe. The most clinically significant adverse event has been cardiac dysfunction syndrome, which occurred in less than 5% of patients. Trastuzumab is not associated with the other commonly observed side effects of chemotherapy, such as alopecia, mucositis, and neutropenia. The results from these studies demonstrate that trastuzumab is active and safe in patients with metastatic HER2-overexpressing breast cancer.
Radiosensitization of chemotherapy-refractory, locally advanced or locally recurrent breast cancer with trastuzumab: a phase II trial. [2022]Trastuzumab (Herceptin), an anti-human epidermal growth factor receptor 2 (HER2) antibody, has been shown to be an effective radiosensitizer in preclinical studies. The present Phase II trial evaluated trastuzumab plus radiotherapy in patients with HER2-positive, chemotherapy-refractory, locally advanced or locoregionally recurrent breast cancer.
Do all patients with advanced HER2 positive breast cancer need upfront-chemo when receiving trastuzumab? Randomized phase III trial SAKK 22/99. [2020]HER2-targeted therapy plus chemotherapy is standard treatment in advanced HER2+ breast cancer. Trastuzumab alone followed by addition of chemotherapy at disease progression versus upfront combination therapy has not been elucidated.
Trastuzumab. [2016]Breast cancer is a heterogenous disease with several clinical and biologic subtypes. Human epidermal growth factor receptor 2 (HER 2) is overexpressed in approximately 20% of breast cancers. This overexpression is usually due to HER 2 gene amplification, and results in a more aggressive tumor with a worse prognosis. Trastuzumab (Herceptin((R))) is the first humanized monoclonal antibody to be commercially available for the treatment of breast cancer and it is directed against HER 2. Trials have demonstrated trastuzumab's activity in metastatic breast cancer both as a single agent and in combination with a number of chemotherapy agents. Recently, benefits for trastuzumab have also been shown in the neoadjuvant and adjuvant setting.