Is trastuzumab or Phesgo (pertuzumab and trastuzumab) more effective as an adjuvant treatment for Human Epidermal growth factor Receptor 2 (HER2)-positive breast cancer?

From the Guidelines

Phesgo (pertuzumab and trastuzumab) is generally more effective than trastuzumab alone as adjuvant treatment for HER2-positive breast cancer, particularly in high-risk patients with node-positive or hormone receptor-negative disease. The combination therapy in Phesgo provides dual HER2 blockade, targeting different domains of the HER2 receptor, which results in more complete pathway inhibition.

Key Points

• Clinical trials, particularly the APHINITY trial, demonstrated that adding pertuzumab to trastuzumab and chemotherapy improved invasive disease-free survival compared to trastuzumab and chemotherapy alone 1.
• Phesgo is typically administered subcutaneously, with a loading dose of 1,200 mg pertuzumab/600 mg trastuzumab followed by maintenance doses of 600 mg pertuzumab/600 mg trastuzumab every three weeks for a total treatment duration of one year.
• The subcutaneous formulation offers greater convenience with shorter administration time compared to intravenous infusions.
• Both treatments require baseline cardiac assessment with echocardiogram or MUGA scan and regular cardiac monitoring during treatment due to potential cardiotoxicity, as recommended by recent guidelines 1.
• While Phesgo offers improved efficacy, treatment selection should consider individual patient factors including risk of recurrence, comorbidities, and cost considerations, as well as the potential benefits and risks of dual blockade with pertuzumab and trastuzumab in the adjuvant setting, as discussed in recent consensus conferences 1.

Administration and Monitoring

• The treatment duration for trastuzumab has been established as 12 months, although some studies suggest that 6 months may be non-inferior for patients with low risk of recurrence and comorbidities 1.
• Regular cardiac assessments are recommended before, during, and after therapy, with the option of additional assessments before the start of any chemotherapy treatment 1.

From the FDA Drug Label

The effectiveness of PHESGO for use in combination with chemotherapy has been established for the treatment of patients with HER2-positive early breast cancer Use of PHESGO for this indication is supported by evidence from adequate and well-controlled studies conducted with intravenous pertuzumab and intravenous trastuzumab administered in combination with chemotherapy in adults with HER2-overexpressing early breast cancer The FeDeriCa trial (NCT03493854) was an open-label, multicenter, randomized trial conducted in 500 patients with operable or locally advanced (including inflammatory) HER2-positive breast cancer with a tumor size >2 cm or node-positive Table 6: Summary of Pathological Complete Response (pCR) (FeDeriCa) PHESGOn=248Intravenous pertuzumab + trastuzumabn=252 * Confidence interval for one sample binomial using Pearson-Clopper method † Hauck-Anderson continuity correction has been used in this calculation pCR: ypT0/is, ypN0148 (59.7%)150 (59.5%) Exact 95% CI for pCR Rate*(53.3%, 65.8%)(53.2%, 65.

Both PHESGO and trastuzumab (as part of intravenous pertuzumab and trastuzumab) have been shown to be effective as adjuvant treatments for HER2-positive breast cancer.

• The pathological complete response (pCR) rates were similar between the two groups: 59.7% for PHESGO and 59.5% for intravenous pertuzumab and trastuzumab.
• The study demonstrated non-inferiority of PHESGO compared to intravenous pertuzumab and trastuzumab in terms of pertuzumab serum Ctrough levels. Based on the available data from the FeDeriCa trial 2, it can be concluded that PHESGO is as effective as trastuzumab (as part of intravenous pertuzumab and trastuzumab) as an adjuvant treatment for HER2-positive breast cancer.

From the Research

Adjuvant Treatment for HER2-Positive Breast Cancer

The choice between trastuzumab and Phesgo (pertuzumab and trastuzumab) as an adjuvant treatment for Human Epidermal growth factor Receptor 2 (HER2)-positive breast cancer depends on various factors, including the patient's overall health, tumor characteristics, and potential side effects.

Efficacy of Trastuzumab

• Trastuzumab has been shown to improve disease-free survival (DFS) and overall survival (OS) in patients with HER2-positive early-stage breast cancer when combined with chemotherapy 3, 4.
• The addition of trastuzumab to adjuvant chemotherapy has been associated with a lowered risk of death and relapse by one-third 3.
• However, trastuzumab use has also been linked to an increased risk of cardiotoxicity, with two to three times more risk of heart toxicity effects compared to chemotherapy alone 3.

Efficacy of Phesgo (Pertuzumab and Trastuzumab)

• Pertuzumab, in combination with trastuzumab, has been shown to be beneficial for the treatment of metastatic cancer, advanced local cancer, or early cancer by dual HER2 blockage 5, 6.
• The combination of pertuzumab and trastuzumab has been associated with improved outcomes in patients with HER2-positive breast cancer, including increased DFS and OS 5, 6.
• However, pertuzumab use has also been linked to an increased risk of cardiac toxicity, although the risk is considered low 5.

Comparison of Trastuzumab and Phesgo

• The APHINITY trial, which compared the efficacy of pertuzumab and trastuzumab with trastuzumab alone in the adjuvant setting, showed that the combination of pertuzumab and trastuzumab improved invasive DFS, although the benefit was modest 5.
• The choice between trastuzumab and Phesgo should be individualized based on patient characteristics, tumor biology, and potential side effects 5, 6.

Potential Side Effects

• Both trastuzumab and Phesgo have been associated with potential side effects, including cardiotoxicity, diarrhea, and other adverse events 3, 5, 6.
• The risk of cardiac toxicity is a significant concern with both trastuzumab and Phesgo, and patients should be closely monitored for signs of cardiac dysfunction 3, 5.