What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those involving Tyrosine Kinase Inhibitors (TKIs) like Neratinib, often lead to side effects such as diarrhea, nausea, fatigue, and liver toxicity. Other treatments, such as tamoxifen, can cause hot flashes, increased risk of thromboembolic events, and endometrial cancer. Aromatase inhibitors, another common treatment, are associated with bone density loss, fractures, and cardiovascular risks. These side effects should be discussed with a healthcare provider to manage and mitigate their impact on quality of life.

What prior FDA approvals exist?

The FDA has approved several treatments for HER2-positive breast cancer, including trastuzumab (Herceptin), pertuzumab (Perjeta), and ado-trastuzumab emtansine (T-DM1). Trastuzumab is a monoclonal antibody that targets the HER2 receptor, while pertuzumab is another monoclonal antibody that works synergistically with trastuzumab. T-DM1 is an antibody-drug conjugate combining trastuzumab with the cytotoxic agent emtansine. Neratinib, a tyrosine kinase inhibitor targeting HER2 and EGFR, has also been approved for extended adjuvant treatment following trastuzumab-based therapy. These treatments have significantly improved outcomes for patients with HER2-positive breast cancer.

What other types of research exist?

Promising alternatives to Neratinib for breast cancer patients include Tucatinib, a TKI targeting HER2, which has shown efficacy in combination with trastuzumab and capecitabine. Another option is Trastuzumab Deruxtecan, an antibody-drug conjugate targeting HER2, which has demonstrated significant activity in HER2-positive breast cancer. Additionally, Pyrotinib, a pan-HER TKI, has shown promising results in clinical trials. These therapies offer novel mechanisms of action and have been effective in patients with HER2-positive breast cancer.

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Aromatase Inhibitor

Neratinib + Endocrine Therapy + Trastuzumab for Breast Cancer

Phase 2

Recruiting

Led By Ruth O'Regan, MD

Research Sponsored by Ruth O'Regan

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 weeks

Awards & highlights

No Placebo-Only Group

Summary

This trial involves treating breast cancer patients with three drugs: neratinib, an aromatase inhibitor, and trastuzumab. These drugs work together to block cancer growth signals, lower estrogen levels, and help the immune system attack cancer cells. The treatment is aimed at patients with HER2-positive breast cancer who may not respond well to standard treatments. Trastuzumab is a well-established treatment for HER2-positive breast cancer, often used in combination with other therapies.

Who is the study for?

This trial is for postmenopausal women over 18 with stage I-III invasive breast cancer that's larger than 10mm, HER2-positive, and ER-positive. Candidates must have a good performance status, resectable cancer suitable for pre-op therapy, agree to biopsies, and have proper heart function. Excluded are those needing strong CYP3A4 inhibitors/inducers or with active infections, recent major surgery side effects, GI issues affecting drug absorption, metastatic disease or certain cardiovascular conditions.

What is being tested?

The study tests the combination of Neratinib (a targeted therapy), an aromatase inhibitor (Letrozole or Anastrozole), and Trastuzumab (an immune therapy) given for 24 weeks before surgery in treating HER2-positive breast cancer. The initial three weeks involve varying combinations of these drugs followed by standard care after surgery.

What are the potential side effects?

Potential side effects include diarrhea from Neratinib; Letrozole or Anastrozole may cause hot flashes and joint pain; Trastuzumab can lead to heart problems and infusion reactions. Side effects vary among individuals.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Pathologic Complete Response (pCR)

Secondary study objectives

Assess Adverse Events

Measure Residual Disease

Pathological Complete Response (pCR)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: AExperimental Treatment3 Interventions

Weeks 1-3\* patients receive either (a) Neratinib, (b) Letrozole or Anastrozole or (c) Neratinib + Letrozole or Anastrozole Weeks 4-24 patients receive Neratinib + Letrozole or Anastrozole and Trastuzumab \*Starting drug intervention varies for the first 3 weeks depending on arms: a, b, and c by randomization.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Neratinib

2014

Completed Phase 2

~1970

Trastuzumab

2014

Completed Phase 4

~5190

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for breast cancer, particularly those targeting HER2 and EGFR, include Tyrosine Kinase Inhibitors (TKIs) like Neratinib and monoclonal antibodies like Trastuzumab. TKIs work by blocking the enzymatic activity of tyrosine kinases, which are involved in the signaling pathways that promote cancer cell growth and survival. Monoclonal antibodies, on the other hand, bind to specific proteins on the surface of cancer cells, marking them for destruction by the immune system or blocking the signals that stimulate their growth. These targeted therapies are important for breast cancer patients as they offer a more personalized treatment approach, potentially leading to better outcomes and fewer side effects compared to conventional chemotherapy.

Resistance mechanisms of epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer patients: A meta-analysis.Targeted Approaches Applied to Uncommon Diseases: A Case of Salivary Duct Carcinoma Metastatic to the Brain Treated with the Multikinase Inhibitor Neratinib.