# CDK4/6 Inhibitors in Patients Aged 80 and Older with HR+/HER2− Metastatic Breast Cancer: A Real-World Multicenter Study

## TL;DR

This study shows that CDK4/6 inhibitors can be safely and effectively used in patients aged 80 and older with a specific type of breast cancer, with outcomes similar to younger patients.

## Contribution

The study provides real-world evidence on the safety and efficacy of CDK4/6 inhibitors in patients aged 80 and older with HR+/HER2− metastatic breast cancer.

## Key findings

- Treatment with CDK4/6 inhibitors in patients aged ≥80 was feasible and well tolerated with comparable survival outcomes to younger populations.
- Hematologic toxicity was common but mostly manageable, with neutropenia affecting 58.8% of patients.
- Median progression-free survival was 13 months and median overall survival was 15 months in this elderly cohort.

## Abstract

Older adults aged 80 years and above are rarely included in clinical trials evaluating cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, leaving clinicians with little evidence to guide treatment decisions in this growing patient population. We conducted a multicenter, retrospective study across seven Italian oncology units to describe real-world outcomes of patients aged ≥80 years with HR+/HER2− metastatic breast cancer treated with CDK4/6 inhibitors plus endocrine therapy. Despite frailty and frequent comorbidities, treatment was feasible and generally well tolerated, with survival outcomes comparable to those reported in younger populations. These findings support individualized treatment strategies and suggest that advanced age alone should not preclude the use of CDK4/6 inhibitors

Background: Older adults aged ≥80 with HR+/HER2− metastatic breast cancer (MBC) are often underrepresented in clinical trials, leaving clinicians with limited data to guide treatment decisions. Given the increasing prevalence of this age group, real-world evidence is crucial to inform therapeutic strategies. Methods: We performed a multicenter retrospective study across seven Italian oncology units, focusing on patients aged 80 or above who received CDK4/6 inhibitors in combination with endocrine therapy between January 2020 and May 2024. Baseline characteristics, treatment details, and adverse events were recorded. Primary endpoints were progression-free survival (PFS) and overall survival (OS); toxicity was assessed using CTCAE v5.0. Follow-up was estimated using the reverse Kaplan–Meier method. Results: Eighty patients were included, with a median age of 83. Over half had visceral metastases, and 41.0% were frail (G8 ≤ 14). Approximately 44.0% of patients started treatment at a reduced dose. The median PFS was 13 months (95.0% CI 9.3–18.0), and the median OS was 15 months (95.0% CI 11.8–18.2). Hematologic toxicity was frequent, with neutropenia occurring in 58.8% (25.0% grade ≥ 3) and anemia in 12.5% (2.5% grade ≥ 3). Asthenia was reported in 16.2% (5.0% grade ≥ 3). Diarrhea occurred in 3.8% overall, mainly in patients treated with abemaciclib (42.9% any grade; 14.3% grade ≥ 3). ALT/AST elevations were observed in 8.8% (1.2% grade ≥ 3), and QTc prolongation in 2.5% (1.2% grade ≥ 3, all with ribociclib). Grade ≥ 3 events were uncommon and generally manageable. Conclusions: CDK4/6 inhibitor-based therapy is feasible in patients aged ≥80 years, with outcomes and tolerability comparable to those observed in younger elderly. Our results highlight the importance of individualized treatment strategies in this oldest-old population.