Prognostic value of cachexia index in HR +/HER2 - metastatic breast cancer treated with CDK4/6 inhibitors.

PURPOSE: The prognostic significance of body composition parameters in patients with HR + /HER2 − metastatic breast cancer treated with CDK4/6 inhibitors remains poorly defined. The cachexia index (CXI), a composite marker integrating skeletal muscle mass, nutritional status, and systemic inflammation, may provide additional prognostic information in this setting. This study aimed to evaluate the prognostic value of body composition parameters, with a particular focus on CXI, in this patient population.

METHODS

This retrospective single-center study included 84 patients with HR + /HER2 − metastatic breast cancer receiving CDK4/6 inhibitor therapy. Body composition parameters were assessed using baseline imaging at the L3 vertebral level. Sarcopenia was defined as skeletal muscle index (SMI) < 38.5 cm2/m2. CXI was calculated as [skeletal muscle index × serum albumin]/neutrophil-to-lymphocyte ratio. Prognostic factors were evaluated using univariate and multivariate Cox regression analyses.

RESULTS

At a median follow-up of 42.0 months, median PFS and OS were 40.8 and 49.6 months, respectively. The median SMI was 32.1 cm2/m2 (IQR 25.2–39.9). Sarcopenia was present in 50 patients (64.3%). Patients with high CXI (≥ 44.9) demonstrated significantly longer PFS (not reached vs. 26.3 months, p = 0.001) and OS (not reached vs. 33.3 months, p = 0.004) compared to those with low CXI. In multivariate analysis, high CXI independently predicted reduced risk of disease progression (HR 0.34, 95% CI 0.16–0.71, p = 0.004) and death (HR 0.26, 95% CI 0.11–0.61, p = 0.002). While sarcopenia and low skeletal muscle density were associated with inferior outcomes in univariate analysis, only CXI retained independent prognostic significance after adjustment for confounding factors including liver metastases and luminal subtype.

CONCLUSION

In this study, we demonstrated that CXI serves as an independent prognostic biomarker for both PFS and OS in patients with HR + /HER2 − metastatic breast cancer treated with CDK4/6 inhibitors. CXI, a cost-effective tool that can be easily obtained from routine imaging and laboratory parameters, has the clinical capacity to facilitate risk classification and guide the multidisciplinary supportive interventions.