Factors Linked to Survival Outcomes in Mets Breast Cancer

TOPLINE:

In patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (ERBB2)–negative metastatic breast cancer who progressed following endocrine plus cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy, longer duration of CDK4/6 inhibitor therapy was associated with improved overall survival, while the presence of visceral metastases was associated with worse overall survival. Following progression, oral chemotherapy could be a preferred option for select patients, the authors reported. 

METHODOLOGY:

• Most patients with HR-positive, ERBB2-negative metastatic breast cancer progress following first-line endocrine therapy and CDK4/6 inhibitor treatment. How various clinicopathologic characteristics and treatment types affect survival outcomes in this patient population remains unclear, as is the optimal therapy after progression.
• To identify factors that may be linked to survival outcomes, researchers analyzed outcomes from 506 women (median age at diagnosis, 52.4 years) with HR-positive, ERBB2-negative metastatic breast cancer who progressed during first- or second-line endocrine therapy plus CDK4/6 inhibitor treatment.
• Overall, 67.6% received endocrine therapy and CDK4/6 inhibitor agents as first-line treatment and 32.4% received that combination as second-line treatment. Following progression, 221 patients received endocrine therapy (everolimus plus exemestane or endocrine therapy alone), and 285 patients received chemotherapy (single-agent or combination intravenous chemotherapy or oral chemotherapy).
• The primary endpoint was progression-free survival (PFS), defined as time between initiating the first systemic treatment and the detection of disease progression or any-cause death; the secondary endpoint was overall survival, defined as the time interval between tumor progression during endocrine therapy plus CDK4/6 inhibitor therapy and any-cause death.

TAKEAWAY:

• In this population who progressed following endocrine therapy and CDK4/6 inhibitor treatment, the presence of visceral metastases and de novo metastatic disease were independently associated with a higher risk for disease progression or death (hazard ratio [HR], 1.45 and 1.25, respectively), whereas older age was associated with slightly better PFS (HR, 0.99; P = .03).
• Longer duration of CDK4/6 inhibitor therapy (exceeding 12 months) was associated with significantly better overall survival (HR, 0.55), whereas the presence of visceral metastases was associated with significantly worse overall survival (HR, 1.63).
• Compared with oral chemotherapy, intravenous chemotherapy and endocrine therapy were associated with shorter PFS (HR, 1.45 and 1.38, respectively) but not significantly different overall survival.
• Among patients with visceral metastases, use of intravenous chemotherapy was associated with significantly shorter overall survival compared with oral chemotherapy (HR, 1.52; P = .04).

IN PRACTICE:

“In this cohort study of 506 patients diagnosed with hormone receptor-positive, ERBB2-negative metastatic breast cancer progressing during endocrine therapy plus CDK4/6 inhibitor treatment, our findings suggest that oral chemotherapy could be a preferred option for select patients with visceral metastases, offering comparable survival outcomes with potentially fewer adverse effects and greater convenience,” the authors wrote.

SOURCE:

This study, led by Pier Paolo Maria Berton Giachetti, MD, Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology IRCCS, Milan, Italy, was published online in JAMA Network Open.

LIMITATIONS:

The retrospective design might have introduced selection bias and uncontrolled confounding factors. Patients receiving a second CDK4/6 inhibitor therapy after tumor progression during the initial CDK4/6 inhibitor therapy were excluded. Data on relevant tumor genomic alterations could not be collected, limiting the assessment of the potential association between these tumor mutations and treatment outcomes.

DISCLOSURES:

No funding information was provided for the study. Several authors reported receiving grants and honoraria and having other ties with various sources. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.