Atirmociclib/Fulvestrant Improves PFS in HR+/HER2– Breast Cancer

The primary end point of progression-free survival (PFS) was met in the phase 2 FOURLIGHT-1 trial (NCT06105632), which assessed atirmociclib plus fulvestrant (Faslodex) compared with fulvestrant or everolimus (Afinitor) plus exemestane for patients with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer who experienced progression after previous CDK4/6 inhibitor treatment.¹

The results showed a statistically significant and clinically meaningful improvement in PFS, which was assessed by the investigator (HR, 0.60; 95% CI, 0.440-0.825; P = .0007). The press release noted that the results for PFS were consistent across subgroups, including performance status, menopausal status, presence of visceral disease, duration of prior treatment with CDK4/6 inhibitor, and regardless of prior CDK4/6 inhibitor. Within 3 months of their last CDK4/6 inhibitor cancer treatment, more than 90% of patients initiated atirmociclib treatment.

At the data cutoff, the key secondary end point of overall survival (OS) was not mature. Approximately 20% of patients experienced an OS event.

A “manageable” safety profile was noted with atirmociclib, with 6.4% of patients discontinuing treatment because of treatment-emergent adverse effects. These results were consistent with previously published studies.

“These results are especially encouraging given that the FOURLIGHT‑1 study enrolled patients whose disease had progressed soon after prior CDK4/6 inhibitor therapy, a difficult-to-treat population,” Jeff Legos, chief oncology officer at Pfizer, said in the press release.¹ “The strength of these data reinforces our confidence that atirmociclib may meaningfully differentiate from the CDK4/6 inhibitor class, the standard-of-care backbone in [hormone receptor]–positive breast cancer, with the potential for improved efficacy and tolerability. We are continuing to accelerate development of this next-generation cell cycle inhibitor in earlier lines of therapy where it may offer even greater benefit for patients.”

At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, findings from this study were presented in a poster as a trial in progress by Antonio Giordano, MD, from Dana-Farber Cancer Institute.² Patients were randomly assigned 1:1 to either the investigational arm of atirmociclib continuously for 28 days orally plus fulvestrant given as an intramuscular injection on days 1 and 15 of cycle 1 and then on day 1 of each cycle after. The comparator arm was comparable, with patients receiving the same fulvestrant dosing, or everolimus plus exemestane given orally in a 28-day cycle.

Additional secondary end points of the trial included objective response by investigator per RECIST v1.1, duration of response, number of patients with clinical benefit response, and number of patients with adverse effects.

Patients were included in the trial if they had histological confirmation of breast cancer with evidence of locally advanced or metastatic disease which is not amenable to surgical resection or radiation therapy with curative intent; documented estrogen receptor and/or progesterone receptor–positive disease; documented HER2-negative tumor; sufficient amount of representative formalin fixed, paraffin embedded tumor tissue specimen; previously received a CDK4/6 inhibitor plus non-steroidal aromatase inhibitor; measurable disease or non-measurable bone only disease defined by RECIST v1.1; and an ECOG performance status of 2 or less.³

Patients were excluded from treatment if they had any medical or psychiatric condition that may increase the risk of study participation or make the participant inappropriate for the study, a visceral crisis at risk of immediately life-threatening complications in the short-term, uncontrolled or symptomatic central nervous system metastases, radiation within 2 weeks of randomization, or inadequate renal function.

References

1. 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. Accessed March 17, 2026. https://tinyurl.com/jy4fkvsu
2. Girodana A, Ignatiadis M, Barrios C, et al. International phase 3 clinical trial evaluating PF-07220060 plus fulvestrant in patients with HR+/HER2− advanced/metastatic breast cancer with progression after a prior CDK4/6 inhibitor. J Clin Oncol. 42, 2024 (suppl 16):TPS1129. doi:10.1200/JCO.2024.42.16_suppl.TPS1129
3. A study to learn about the study medicine called PF-07220060 in combination with fulvestrant in people with HR-positive, HER2-negative advanced or metastatic breast cancer who progressed after a prior line of treatment. ClinicalTrials.gov. Updated February 13, 2026. Accessed March 17, 2026. https://tinyurl.com/zh6m83je