ASCO Michigan 2024: Dr. Chen Discusses Outcomes from postMONARCH in Metastatic Breast Cancer

Presenter:

Nan Chen, MD, University of Chicago

Conference:

ASCO Direct™ Michigan

The Bottom Line:

Treatment options have expanded for patients with advanced, hormone receptor-positive (HR+), Human epidermal growth factor receptor 2 negative (HER2-) breast cancer who have progressed following first line therapy with a cyclin dependent kinase 4/6 inhibitor (CDK4/6i) and endocrine therapy (ET).  Results from the postMONARCH trial demonstrate that the addition of abemaciclib to a selective estrogen receptor degrader (SERD), fulvestrant, improved progression free survival as compared to fulvestrant alone.  Additional findings showed that the benefit of adding abemaciclib was most pronounced in patients without visceral metastasis (e.g., lung or liver disease) as compared to those with visceral metastasis, and in those whose prior CDK4/6i treatment was 12 months or longer, as compared to those who recurred sooner.

 Background

Patients with advanced, HR+/HER2- breast cancer that has spread beyond the primary site (metastatic disease) typically receive initial treatment with a CDK4/6i (abemaciclib, ribociclib, or palbociclib) in combination with an endocrine therapy (ET), such as tamoxifen or an aromatase inhibitor (AI).  Following progression, treatment options include a change in their CDK4/6i, or, for patients with mutations in the estrogen receptor gene, ESR1, a selective estrogen receptor degrader (SERD) such as fulvestrant.  An orally administered tyrosine kinase inhibitor (TKI) type therapy can also be considered for patients who have specific molecular alterations in their tumors, such as alterations in the AKT pathway.  In her presentation at the ASCO Direct™ Michigan conference, Dr Nan Chen from The University of Chicago highlighted the primary results from the postMONARCH Trial, as reported at the 2024 American Society for Clinical Oncology (ASCO) Meeting.

Patients and Trial Design

The phase III postMONARCH Trial examined the use of a CDK4/6i (abemaciclib) in combination with a SERD (fulvestrant) as compared with fulvestrant alone, in HR+/HER- advanced breast cancer patients who had progression on prior CDK4/6i + ET, and the primary endpoint in the trial was progression free survival (PFS). Notably, about two thirds of patients in the trial had visceral metastases, mostly to the liver, most had received initial CDK4/6i therapy with palbociclib, and the majority of patients had been on their CDK4/6i therapy for 12 months or longer.

Key Efficacy Findings

The results showed a modest, but statistically significant improvement in PFS with abemaciclib + fulvestrant versus fulvestrant alone with a median PFS of 6.0 months versus 5.3 months in the abemaciclib and placebo arms, respectively (Box 1), corresponding to a 27% relative improvement in PFS (hazard ratio [HR] = 0.73P=0.02). Additional findings showed that, while the benefit of adding abemaciclib over fulvestrant alone was generally seen in all subgroups of patients, there was a greater benefit observed in patients who had been on their prior CDK4/6i for 12 months or longer, relative to those patients who had relapsed within their first year on a CDK4/6i + ET (Box 1). Similarly, when comparing outcomes in those patients with or without visceral metastases at baseline, those without visceral metastases had a greater benefit of adding abemaciclib as compared to those with visceral metastases (Box 1).

Box 1.  PFS Benefit of Abemaciclib + Fulvestrant Over Fulvestrant Alone in Advanced HR+/HER2- Breast Cancer

Dr Chen further noted that most patients in postMONARCH (59%) had received palbociclib as their prior CDK4/6i, and about 34% had received ribociclib as initial treatment.  In this regard, she noted results from the subgroup analysis, which also showed there was a benefit of abemaciclib and fulvestrant treatment for patients who had received prior palbociclib (HR=0.62; meaning a 38% PFS improvement with treatment), while those receiving prior ribociclib did not appear to benefit (HR=1.01; meaning no improvement). 

Conclusions and Faculty Insights:

Commenting on the overall results of the trial, Dr Chen noted that, at present, there are no criteria, or “biomarkers” that can determine the optimal treatment for patients with HR+/HER2- advanced breast cancer following progression on initial CDK4/6i + ET.  Based on results from postMONARCH, however, she notes that selection of patients may be important.  As such, she would consider those receiving prior palbociclib, those without visceral metastases, and those with a longer duration of their prior CDK4/6i + ET treatment (i.e., 1 year or longer) as most appropriate for the postMONARCH regimen.

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Speaker Disclosure:

Dr. Chen reported the following disclosures for this presentation: Consultant Fees: Seagen, Guardant Health, Stemline, Novartis; Institutional Research Funding: Eli Lilly.