The CDK4/6 inhibitor and aromatase inhibitor combination produced a 32% ORR and 48% clinical benefit rate at 6 months.
Palbociclib (Ibrance) plus anastrozole demonstrated clinically meaningful antitumor activity and significant quality-of-life (QOL) improvements in patients with estrogen receptor (ER)–positive recurrent or metastatic low-grade endometrioid endometrial cancer, according to data from a phase 2 study (CTRI/2023/08/056195) presented at the
In 25 evaluable patients, the objective response rate (ORR) at 3 months was 32%, with 1 complete response; the clinical benefit rate (CBR) at 6 months was 48%. At a median follow-up of 20.7 months, the median progression-free survival (PFS) was 6.97 months (range, 3.27-18.43) and median overall survival (OS) had not been reached. QOL improved significantly at 6 months in the global health status and physical functioning domains. Most adverse effects (AEs) were grade 1 or 2 and were manageable with temporary dose interruption.
"We determined that the combination of palbociclib with anastrozole has a clinically meaningful activity with nearly half the patients showing a clinical benefit, as well as significant improvement in QOL across multiple domains," Chitrakshi Nagpal, MD, MBBS, DM, a junior consultant at Apollo Hospitals in India, said during the presentation. "It is well tolerated with most patients experiencing only grade 1 or 2 AEs, easily managed with temporary drug interruption."
The single-arm study enrolled patients with recurrent or metastatic ER-positive low-grade endometrioid endometrial cancer between July 2023 and June 2025. Patients received palbociclib at 125 mg orally once daily on days 1 through 21 of a 28-day cycle plus anastrozole at 1 mg orally once daily on days 1 through 28. Treatment was continued until disease progression, intolerable toxicity, or death. Dose interruption or delay was mandated for uncomplicated grade 3 or febrile neutropenia, grade 4 neutropenia, grade 4 thrombocytopenia, grade ≥3 non-hematologic toxicity, or grade 3 QT prolongation (QTc ≥ 501 ms). Dose reduction levels were 100 mg (level −1) and 75 mg (level −2); patients requiring further reduction were discontinued.
In terms of QOL, significant improvement was observed at 6 months compared with baseline in global health status (mean score, 52.78 at baseline vs 76.85 at 6 months; P = .04) and physical functioning (mean score, 51.85 vs 78.52; P = .01). The cognitive functioning domain showed significant improvement at 3 months (P = .001). Role, emotional, and social functioning domains did not reach statistical significance at either time point, though trends favored improvement at 6 months.
In the safety population, the most common AEs of any grade were anemia (92% any grade; 28% grade 3), fatigue (88.5%; 15.4%), neutropenia (77%; 30%), leukopenia (69.2%; 15.4%), and thrombocytopenia (61%; 0% grade 3). Most AEs were manageable with dose interruption. Seven patients required dose interruption: 5 due to neutropenia, 1 due to hepatitis B reactivation leading to liver dysfunction, and 1 due to transfusion-requiring anemia. Three patients required dose reduction: 2 due to neutropenia and 1 due to recurrent transfusion-requiring anemia.
Investigators concluded that CDK4/6 plus AI combination represents a promising option in patients with ER-positive low-grade endometrial cancers.
