What treatment options are available for a patient with ER+ (estrogen receptor positive) breast cancer who has progressed on ribociclib (Ribociclib) and fulvestrant (Fulvestrant) with liver involvement?

From the Guidelines

For a patient with ER+ breast cancer who has progressed on ribociclib and fulvestrant with liver involvement, the most appropriate next step would be to switch to a different endocrine therapy combined with another targeted agent, such as everolimus (Afinitor) at 10mg daily with exemestane 25mg daily, as recommended by the ASCO guideline update 1. This approach is supported by the guideline's algorithm for endocrine treatment and targeted therapy for HR-positive, HER2-negative metastatic breast cancer, which suggests considering fulvestrant plus alpelisib as second-line therapy for patients with PIK3CA mutations, or chemotherapy as a third-line therapy option 1. The ESMO clinical practice guideline for the diagnosis, staging, and treatment of patients with metastatic breast cancer also recommends considering everolimus with exemestane or fulvestrant as a treatment option for patients with ER-positive/HER2-negative MBC, especially in cases where there is no risk of imminent organ failure 1. Additionally, the 5th ESO-ESMO international consensus guidelines for advanced breast cancer suggest that a CDK4/6 inhibitor combined with endocrine therapy is the standard of care for patients with ER-positive/HER2-negative ABC, but also note that everolimus with an aromatase inhibitor is a valid option for some patients previously exposed to or naive to endocrine therapy 1. Given the liver involvement indicating more aggressive disease, chemotherapy is also a reasonable option, with options including capecitabine, weekly paclitaxel, or eribulin, as mentioned in the example answer. For patients with PIK3CA mutations, alpelisib with fulvestrant could be considered if not previously used, as it provided about 5 months of benefit in median PFS in the SOLAR-1 trial, as noted in the ESMO guideline 1. The choice between these options depends on the patient's performance status, comorbidities, prior toxicities, and disease burden, as well as the presence of any PIK3CA mutations or other biomarkers that may influence treatment decisions, as discussed in the guidelines 1. It is essential to carefully evaluate the patient's individual characteristics and disease status to determine the most appropriate treatment approach, considering the potential benefits and risks of each option, including the toxicity profiles of the targeted agents and chemotherapy regimens, as highlighted in the guidelines and study results 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Treatment Options for ER+ Breast Cancer with Liver Involvement

• For patients with ER+ breast cancer who have progressed on ribociclib and fulvestrant with liver involvement, several treatment options can be considered, including:
  • Other CDK4/6 inhibitors such as palbociclib or abemaciclib in combination with endocrine therapy 2, 3, 4
  • mTOR inhibitors like everolimus in combination with endocrine therapy 5, 4
  • PI3K inhibitors such as alpelisib in combination with endocrine therapy 5
  • Selective estrogen receptor degraders (SERDs) such as fulvestrant 5
  • Aromatase inhibitors (AIs) such as letrozole 3

Considerations for Treatment Selection

• When selecting a treatment, it is essential to consider the patient's previous treatment history, tumor characteristics, and potential toxicities associated with each treatment option 3, 4
• For example, ribociclib has a higher incidence of liver function test abnormalities and QTc prolongation compared to other CDK4/6 inhibitors, which may be a consideration for patients with liver involvement or cardiac comorbidities 3

Emerging Therapies

• New therapies targeting apoptosis, such as venetoclax, a BCL2 inhibitor, and AMG-232, an MDM2 inhibitor, are being explored in clinical trials for ER+ breast cancer 5
• These therapies aim to induce tumor cell death and may offer new treatment options for patients with ER+ breast cancer who have progressed on existing therapies 5

Clinical Trial Data

• Clinical trials have demonstrated the efficacy and safety of various treatment combinations for ER+ breast cancer, including ribociclib plus fulvestrant, which has shown a significant overall survival benefit compared to fulvestrant alone 6
• The MONALEESA-3 trial demonstrated a 28% difference in the relative risk of death in favor of ribociclib plus fulvestrant compared to placebo plus fulvestrant 6