Should Kadcyla (ado-trastuzumab emtansine) be considered in patients with residual disease after treatment without a pathologic complete response (pCR)?

From the Guidelines

Yes, Kadcyla (ado-trastuzumab emtansine) should be considered in patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant therapy containing taxane and trastuzumab. The standard approach is to switch from trastuzumab to Kadcyla for the adjuvant phase of treatment, typically administered at 3.6 mg/kg intravenously every 3 weeks for a total of 14 cycles. This recommendation is based on the KATHERINE trial, which demonstrated that patients who received Kadcyla instead of continuing trastuzumab had a significantly lower risk of recurrence or death, with a 50% reduction in the risk of invasive disease recurrence or death with Kadcyla compared to trastuzumab 1. The presence of residual disease after neoadjuvant therapy indicates a higher risk of recurrence, and Kadcyla's mechanism of action, which combines the targeted effects of trastuzumab with the cytotoxic agent emtansine, provides enhanced efficacy in this setting. Common side effects include fatigue, nausea, thrombocytopenia, elevated liver enzymes, and peripheral neuropathy, which should be monitored during treatment. Additionally, the NCCN guidelines support the use of Kadcyla in this setting, recommending it as an option for patients with residual invasive disease after neoadjuvant therapy 1. Other guidelines, such as the ESMO guidelines, also recommend the use of Kadcyla in patients with residual invasive disease after neoadjuvant therapy, highlighting its efficacy in reducing the risk of recurrence or death 1.

Some key points to consider when using Kadcyla in this setting include:

• Monitoring for side effects, such as liver enzyme elevations and thrombocytopenia
• Administering the drug at the recommended dose and schedule
• Considering the patient's overall risk of recurrence and potential benefits of treatment
• Discussing the potential risks and benefits of treatment with the patient, including the risk of side effects and the potential for improved outcomes.

Overall, the use of Kadcyla in patients with residual invasive disease after neoadjuvant therapy is supported by strong evidence and should be considered as a treatment option for these patients.

From the FDA Drug Label

1.2 Early Breast Cancer (EBC) KADCYLA, as a single agent, is indicated for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment.

Kadcyla should be considered in patients with residual disease after treatment without a pathologic complete response (pCR), as it is indicated for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment 2.

• Key points:
  • Indication: Adjuvant treatment for HER2-positive early breast cancer with residual invasive disease.
  • Patient selection: Based on HER2 protein overexpression or HER2 gene amplification in tumor specimens.
  • Dosing: 3.6 mg/kg given as an intravenous infusion every 3 weeks.

From the Research

Kadcyla Consideration for Residual Disease

• Kadcyla (ado-trastuzumab emtansine) has been approved for the adjuvant treatment of patients with HER2-positive early-breast cancer who have residual invasive disease after neoadjuvant taxane-based chemotherapy and trastuzumab-based treatment 3.
• The KATHERINE trial showed that ado-trastuzumab emtansine significantly improved invasive disease-free survival (iDFS) compared to trastuzumab in patients with residual invasive disease after neoadjuvant therapy 3.
• A narrative review suggested that escalation of adjuvant therapy, including ado-trastuzumab emtansine, is recommended for patients with HER2-positive inflammatory breast cancer with residual disease after neoadjuvant therapy 4.

Pathologic Complete Response and Residual Disease

• Achieving a pathologic complete response (pCR) after neoadjuvant chemotherapy is a surrogate marker for disease-free survival (DFS) and overall survival (OS) in breast cancer patients 5.
• Patients with residual disease after neoadjuvant therapy have a higher risk of recurrence and death, highlighting the need for better therapies 5.
• A study found that residual ductal carcinoma in situ (DCIS) after neoadjuvant chemotherapy did not significantly impact DFS or OS compared to complete pathologic response without residual DCIS 6.

Prognostic Factors for Residual Disease

• Pathological node positivity, supraclavicular lymph node metastasis, and lymphovascular invasion are significant prognostic factors for poor disease-free survival in patients with residual pathological disease after neoadjuvant therapy 7.
• Multifocal disease and stage III disease are more prevalent in patients with residual DCIS after neoadjuvant chemotherapy 6.