What are the next treatment options for a 72-year-old woman with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1, metastatic estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer with metastases to the liver and bone, who has progressed on endocrine therapy, Cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors, Taxol (paclitaxel), Adriamycin (doxorubicin)/Cytoxan (cyclophosphamide), Gemcitabine/Carboplatin, Xeloda (capecitabine), Enhertu (trastuzumab deruxtecan) and Sacituzumab govitecan, and is not interested in hospice care?

From the Guidelines

For this 72-year-old woman with metastatic ER-positive, HER2-negative breast cancer who has exhausted multiple lines of therapy including endocrine therapy with CDK4/6 inhibitors, chemotherapy regimens, and antibody-drug conjugates, I would recommend eribulin (Halaven) at 1.4 mg/m² IV on days 1 and 8 of a 21-day cycle. Eribulin is a microtubule inhibitor with a unique mechanism of action that has shown efficacy in heavily pretreated metastatic breast cancer patients, as demonstrated in a phase III trial where eribulin improved overall survival compared to treatment of physician's choice 1. Prior to starting treatment, she should have baseline labs including CBC, comprehensive metabolic panel, and liver function tests, with monitoring throughout therapy. Side effects to watch for include neutropenia, peripheral neuropathy, and fatigue. If eribulin is not tolerated or unavailable, vinorelbine (25-30 mg/m² IV weekly) could be considered as an alternative, given its activity in heavily pretreated patients 1. Given her extensive prior treatments and progressive disease, the goals of care should be discussed, focusing on quality of life and symptom management alongside disease control. While she is not currently interested in hospice, early palliative care involvement would be beneficial for symptom management, and the option of hospice should be revisited periodically as her disease evolves, as recommended by the ASCO guideline update 1. It's also important to consider the patient's preferences and values in the decision-making process, as well as the potential benefits and risks of each treatment option, including the use of chemotherapy and targeted therapy 1. Additionally, the patient's performance status, comorbidities, and organ function should be taken into account when selecting a treatment regimen, as recommended by the ESMO clinical practice guidelines 1.

Some key points to consider in the management of this patient include:

• The importance of personalized care and patient involvement in decision-making
• The need for ongoing monitoring and adjustment of treatment plans as the disease evolves
• The potential benefits and risks of each treatment option, including chemotherapy, targeted therapy, and palliative care
• The importance of addressing symptoms and improving quality of life, in addition to controlling the disease
• The need for early palliative care involvement and consideration of hospice care as the disease progresses.

From the FDA Drug Label

1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 14.1 Combination Use with Cisplatin 14.2 Single Agent

The patient has metastatic ER positive HER2 negative breast cancer with progression in the liver, and has been on several lines of treatment.

• Vinorelbine is an option for the treatment of breast cancer.
• The patient's ECOG PS 1 indicates that she is still relatively active and able to carry on with daily activities, which is a consideration for treatment.
• Given the patient's extensive treatment history, including all lines of endocrine therapy/CDK 4/6 inhibitors, taxol, adriamycin/cytoxan, Gemcitabine/carboplatin, xeloda, Enhertu and Sacituzumab govetecan, vinorelbine could be considered as a next step.
• However, it is essential to carefully evaluate the patient's hepatic function before initiating vinorelbine treatment, as it can cause hepatic toxicity 2.
• The decision to use vinorelbine should be made with caution, considering the patient's age and performance status, as well as the potential adverse reactions associated with the drug.

From the Research

Treatment Options

• The patient has undergone several lines of treatment, including endocrine therapy, CDK 4/6 inhibitors, taxol, adriamycin/cytoxan, Gemcitabine/carboplatin, xeloda, Enhertu, and Sacituzumab govetecan 3, 4, 5.
• Considering the patient's progression in the liver and lack of interest in hospice, alternative treatment options need to be explored.
• Vinorelbine has been shown to be effective in pretreated advanced breast cancer patients, with an overall response rate of 33% 3.
• However, a study suggesting cross-resistance between eribulin and vinorelbine may limit the efficacy of vinorelbine in patients who have previously received eribulin 4.

Radiation Therapy

• Radiation therapy can be considered as a local treatment option for the patient's liver metastasis.
• A study on concurrent vinorelbine and radiation therapy in high-risk postmastectomy breast cancer patients showed a manageable safety profile at 10 mg/m2 6.
• Another study on eribulin combined with radiation therapy in a patient with breast cancer showed that the treatment was well-tolerated with no acute toxicity reported 7.

Comparison of Treatment Options

• A randomized clinical trial comparing eribulin and vinorelbine in women with locally recurrent or metastatic breast cancer showed that eribulin achieved statistically significantly superior progression-free survival and response rate compared to vinorelbine 5.
• The study also found that eribulin was better tolerated than vinorelbine, with fewer treatment-emergent adverse events leading to treatment discontinuation 5.