FOURLIGHT-1 Study Data Support Atirmociclib for HR+/HER2- Breast Cancer

Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced or metastatic breast cancer whose disease progressed after previous treatment may have a new therapeutic option on the horizon.

Pfizer Inc. has announced positive topline results from its phase 2 FOURLIGHT-1 study, which found that the investigational drug atirmociclib, when combined with Faslodex (fulvestrant), significantly improved the time patients lived without their cancer worsening compared to those receiving Faslodex or a combination of Afinitor (everolimus) and Aromasin (exemestane). This study marks a potential advancement for individuals who have already received a cyclin-dependent kinase (CDK) 4/6 inhibitor-based treatment, addressing a significant need for more effective therapies in later lines of care.

Main data that support the findings

The study met its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) as assessed by investigators. Patients receiving the atirmociclib combination saw a hazard ratio of 0.60, indicating a lower risk of disease progression for those on the investigational treatment compared to the control group.

The benefits of atirmociclib were consistent across all prespecified groups of patients. These findings held true regardless of:

• Menopausal status
• Performance status
• The presence of visceral disease (cancer that has spread to internal organs)
• Which specific CDK4/6 inhibitor a patient had taken previously
• Whether the previous CDK4/6 treatment lasted more or less than 12 months

Most participants in the study (more than 90%) began their treatment with atirmociclib within three months of finishing their last CDK4/6 inhibitor therapy. While the study is also tracking overall survival (OS) as a secondary endpoint, those data were not yet mature at the time of this analysis, as only approximately 20% of participants had experienced an event.

Jeff Legos, Chief Oncology Officer at Pfizer, noted in a news release from the company that these results are especially encouraging because the study included patients whose disease progressed quickly after prior therapy. He stated that the strength of the data reinforces confidence that atirmociclib may differentiate itself from current standard-of-care CDK4/6 inhibitors by offering improved efficacy and better tolerability for patients.

Trial details

FOURLIGHT-1 is an interventional, open-label, randomized, multicenter phase 2 study. It was designed to compare atirmociclib plus Faslodex against either Faslodex alone or Afinitor plus Aromasin. The trial included 264 patients across 14 countries.

The study focused on adults with HR-positive, HER2-negative advanced or metastatic breast cancer who had previously experienced disease progression following a CDK4/6 inhibitor-based regimen. In addition to measuring progression-free survival, researchers are evaluating secondary outcomes such as:

• Overall survival
• Objective response (the percentage of patients whose cancer shrinks or disappears)
• Duration of response
• Clinical benefit response

Atirmociclib is an oral medication that inhibits CDK4, a protein that triggers the cell cycle and causes cancer cells to grow. Because it is a next-generation inhibitor, researchers are investigating its use in both metastatic and early-stage disease. Currently, a phase 3 registrational study is ongoing for the first-line metastatic setting, and further data regarding its use in early breast cancer will be shared at a future date.

Safety

In the FOURLIGHT-1 trial, atirmociclib showed a manageable safety profile and was well tolerated by the participants. The data revealed that 6.4% of patients had to stop taking atirmociclib due to treatment-emergent side effects.

The safety results were consistent with what researchers had seen in earlier studies of the drug, and no new safety concerns were identified during this phase of testing. Detailed results regarding specific side effects and tolerability will be presented at an upcoming medical meeting. Pfizer indicated that these safety findings support their strategy to move the drug into earlier lines of therapy, where long-term disease control is essential for patients.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

References

“Pfizer Announces Positive Topline Phase 2 Results for Next-Generation CDK4 Inhibitor, Atirmociclib, in Second-Line Metastatic Breast Cancer,” news release, Pfizer, March 17, 2026.

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