Real-world study of treatment patterns and outcomes in patients with HR+ breast cancer after progression on CDK4/6 inhibitor therapy.

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) combined with endocrine therapy are the standard of care for metastatic hormone receptor-positive, HER2-negative breast cancer (HR+ MBC). However, systemic therapy options and outcomes after progression on CDK4/6is remain poorly defined. We analyzed real-world treatment patterns and outcomes in patients with advanced HR+ MBC who received systemic therapy following CDK4/6i progression. Methods: We identified all patients with HR+ MBC treated at MD Anderson Cancer Center between January 1, 1997, and December 31, 2024. Kaplan-Meier and log-rank tests compared PFS and OS across post-CDK4/6i therapies, and a multivariable Cox model assessed prognostic factors. Findings: Among 1826 patients (99% female; median follow-up, 32.4 months), the median age at metastatic diagnosis was 56 years, and most were White (72%),with 10% Black, 9% Hispanic, 6% Asian/Pacific Islander, and <1% Native American. Following progression on CDK4/6is, 43% received chemotherapy, 38% targeted therapy, 12% endocrine therapy alone, and 7% investigational agents. Nearly half (48%) had visceral progression. Median PFS on subsequent therapy was 4.73 months (95% CI, 4.40-4.96), with no significant difference by therapy type. CDK4/6i duration ≥12 months was independently associated with improved PFS (HR 0.86; p = 0.021). Interpretation: Following CDK4/6i progression, most patients received chemotherapy, but PFS did not differ significantly across post-CDK4/6i treatment types. As CDK4/6is remain frontline therapy, further studies are needed to optimize treatment sequencing and improve post-CDK4/6i outcomes. Funding: Department of Defense grant (HT9425-24-1-0991) and the National Cancer Institute MDACC Support Grant (P30 CA016672).