Background
Atirmociclib (PF-07220060) is a highly selective and potent oral CDK4 inhibitor sparing other CDKs such as CDK6. We present long-term safety and efficacy data assessing first-line atirmociclib plus letrozole in patients with hormone receptor–positive (HR+)/HER2-negative (HER2–) metastatic breast cancer (NCT04557449).
Methods
Patients with HR+/HER2− metastatic breast cancer who had not received prior systemic anticancer therapy for advanced cancer were enrolled. Patients received atirmociclib (300 mg by mouth twice daily) plus letrozole (2.5 mg by mouth once daily). Objectives were to assess safety/tolerability and anti-tumor activity of atirmociclib plus letrozole.
Results
At data cutoff (February 21, 2025), 34 patients had received first-line atirmociclib plus letrozole. At baseline, median age was 59.0 years (range, 32−84); half of patients underwent prior anticancer surgery and 47.1% received prior (neo)adjuvant therapy. Median duration of treatment was 23.4 months. The most common treatment-related treatment-emergent adverse events (TRAEs) were neutropenia (61.8%; 26.5% grade 3) and leukopenia (41.2%; no grade 3). There were no grade 4/5 TRAEs. Median time to first onset of any grade neutropenia was 16 days (range, 1−194) with a median duration of 69 days (range, 12−611). Median time to first onset of grade 3 neutropenia was 31 days (range, 16−645) with a median duration of 7 days (range, 3−19). Adverse events (AEs) led to 1 or more dose interruptions in 20 patients (58.8%), most often starting in the first 6 cycles (n = 14; 41.2%). AEs led to a single dose reduction in 6 patients (17.6%): 2 in cycles 3 to 6, 1 in cycles 7 to 12, 2 in cycles 13 to 24 and 1 in cycles 25 and beyond. Neutropenia was the only AE resulting in dose interruption in more than 2 patients. Only 1 patient (2.9%) discontinued atirmociclib due to a TRAE. Of 33 patients with measurable disease at baseline, the confirmed objective response rate is 69.7% (all RECIST v1.1 partial responses), with a clinical benefit rate of 93.9%. At a median follow-up duration of 24.8 months, progression-free survival is not yet mature.
Conclusions
At 24.8 months of follow-up, atirmociclib plus letrozole continues to show favorable safety/tolerability and promising efficacy when used as first-line treatment in patients with HR+/HER2− metastatic breast cancer. A randomized phase 3 trial of atirmociclib plus letrozole has been initiated based on these data.
ClinicalTrials.gov Identifier: NCT04557449
Funding source: This work was supported by Pfizer Inc, USA.
Acknowledgments: Medical writing support was provided by Kevin Woolfrey, PhD, of Oxford PharmaGenesis Inc., Wilmington, DE, USA, and was funded by Pfizer Inc.
