From the Guidelines
For patients with HER2-positive metastatic breast cancer, Phesgo (pertuzumab and trastuzumab) with docetaxel should be administered for at least six cycles, if tolerated, in the palliative setting. This recommendation is based on the most recent and highest quality evidence from the ESMO clinical practice guideline for the diagnosis, staging, and treatment of patients with metastatic breast cancer 1. The guideline suggests that docetaxel should be given for at least six cycles, followed by maintenance pertuzumab and trastuzumab until progression [I, A].
The rationale for this regimen is based on the synergistic effect of dual HER2 blockade (pertuzumab targets a different HER2 domain than trastuzumab) combined with the cytotoxic effects of docetaxel, which has shown significant improvement in progression-free survival and overall survival compared to single-agent HER2 blockade 1.
Some key points to consider when administering Phesgo and docetaxel include:
- Monitoring patients regularly with cardiac assessments, as HER2-targeted therapies carry a risk of cardiotoxicity, particularly in patients with pre-existing cardiac conditions or prior anthracycline exposure.
- Considering alternative taxanes (paclitaxel, nab-paclitaxel) if docetaxel is not tolerated 1.
- Adding endocrine therapy (ET) to pertuzumab and trastuzumab maintenance therapy after completing at least six cycles of upfront concomitant chemotherapy for patients with HER2-positive, HR-positive tumors 1.
Overall, the goal of treatment is to maximize progression-free survival and overall survival while minimizing toxicity and maintaining quality of life. The recommended number of cycles for Phesgo and docetaxel is at least six cycles, if tolerated, with ongoing maintenance therapy with Phesgo until disease progression or unacceptable toxicity occurs.
From the Research
Treatment Overview
- The standard first-line therapy for patients with HER2-positive metastatic breast cancer (MBC) is a taxane combined with trastuzumab and pertuzumab 2.
- Phesgo, a fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection, can be administered in approximately 5-8 minutes 3.
Recommended Number of Cycles
- According to the CLEOPATRA study, docetaxel was given for six cycles, or longer at the investigators' discretion, in combination with pertuzumab and trastuzumab 4.
- There is no clear standard for the number of cycles in the fourth line and beyond, with options including margetuximab in combination with chemotherapy, neratinib + capecitabine, or trastuzumab + chemotherapy 2.
Administration and Safety
- The subcutaneous formulation of pertuzumab and trastuzumab has been shown to be non-inferior to IV pertuzumab plus trastuzumab in terms of serum levels and has a comparable incidence of adverse events 3.
- The most common grade 3-4 adverse event in the CLEOPATRA study was neutropenia, with a rate of 49% in the pertuzumab group and 46% in the placebo group 4.
Treatment Sequencing
- The treatment landscape of HER2-positive advanced disease is evolving constantly, with several active therapies being moved to the early-stage setting 2.
- Finding the best treatment sequencing for each patient, developing reliable predictive biomarkers, and understanding the mechanisms of resistance to these drugs are necessary to maximize patient outcomes and quality of life 5.