Eleftha contains Trastuzumab, is a monoclonal antibody utilized primarily in the treatment of HER2-positive breast and gastric cancers. HER2 (human epidermal growth factor receptor 2) is a protein that promotes cell growth; its overexpression is associated with aggressive tumor behavior. Trastuzumab targets this protein, inhibiting cancer cell proliferation. Trastuzumab has significantly improved outcomes for patients with HER2-positive cancers. Ongoing research and the development of novel therapies continue to build upon its success, offering hope for even more effective treatments in the future.

Mechanism of Action

Trastuzumab binds to the extracellular domain of the HER2 receptor, thereby blocking the natural ligand from activating the receptor. This inhibition disrupts downstream signaling pathways essential for cell growth and survival. Additionally, trastuzumab mediates antibody-dependent cellular cytotoxicity (ADCC), recruiting immune cells to destroy the HER2-overexpressing tumor cells.

Medical Uses

Trastuzumab is indicated for:

• Early-Stage Breast Cancer: Used as adjuvant therapy for HER2-positive breast cancer following surgery, chemotherapy, or radiation.

• Metastatic Breast Cancer: Employed in combination with chemotherapy agents like paclitaxel for first-line treatment.

• Gastric Cancer: Applied in cases of HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma.

The standard duration of trastuzumab therapy in early-stage breast cancer is one year, as this has been shown to optimize clinical benefits.

Administration

Traditionally, trastuzumab is administered via intravenous infusion. A subcutaneous formulation combined with hyaluronidase (Herceptin SC or Herceptin Hylecta) has been developed, allowing for a fixed-dose injection under the skin, which can be more convenient for patients.

Adverse Effects

Common side effects include:

• Flu-like symptoms (fever, chills)

• Nausea

• Diarrhea

• Fatigue

• Headache

More severe but less frequent adverse effects encompass:

• Cardiotoxicity: Manifesting as congestive heart failure or decreased left ventricular ejection fraction. Regular cardiac monitoring is recommended during treatment.

• Infusion-Related Reactions: Such as hypersensitivity or anaphylaxis, particularly with the initial dose.

• Pulmonary Toxicity: Including interstitial lung disease and pneumonitis.

Patients should be closely monitored for these adverse effects, and appropriate management strategies should be employed as necessary.

Resistance and Ongoing Research

Despite its efficacy, resistance to trastuzumab can develop. Mechanisms of resistance include alterations in the HER2 receptor, activation of alternative signaling pathways, and failure to elicit an immune response. To overcome resistance, newer agents have been developed:

• Trastuzumab Emtansine (T-DM1): An antibody-drug conjugate combining trastuzumab with the cytotoxic agent emtansine. It delivers chemotherapy directly to HER2-positive cells, minimizing exposure to normal tissues.

• Trastuzumab Deruxtecan: Another antibody-drug conjugate that has shown promise in treating HER2-positive cancers, including those resistant to previous therapies. 

These advancements aim to enhance treatment efficacy and address challenges associated with trastuzumab resistance.