Computed tomography-based analyses of baseline body composition parameters and changes in breast cancer patients under treatment with CDK 4/6 inhibitors.

Purpose: Body composition parameters including muscle and adipose tissue measurements have emerged as prognostic factors in cancer patients. Besides cell cycle regulation, CDK 4 and 6 also control metabolic processes (lipid synthesis, glycolysis, and mitochondrial function). We studied the impact of baseline body composition parameters on response to CDK 4/6 inhibition and changes on body composition during treatment.

Methods: Retrospective study of 50 patients treated at Institut Jules Bordet between December 2016 and August 2019 with endocrine therapy and CDK 4/6 inhibitor as first or second-line treatment for metastatic breast cancer (BC). CT-based body composition analysis was performed at 3 time points. Cox regression and Kaplan-Meier method were used for the association with Progression-free survival (PFS). Changes in body composition parameters were described in means and compared using paired sampled T test.

Results: Baseline sarcopenia was present in 40% of patients and associated with a significantly worse PFS compared to patients without sarcopenia (20.8 vs 9.6 months, HR 2.52; 95% CI 1.02-6.19, p = 0.037). Patients with higher visceral fat index and higher visceral fat density had better PFS (20.8 vs 10.4 months, HR 0.40; 95% CI 0.16-0.99 p = 0.041-stratified for treatment line). No significant alterations in body composition parameters during treatment were observed.

Conclusion: Sarcopenia is a potential early marker of poor prognosis among patients with metastatic BC treated with CDK 4/6 inhibitors. CT scan evaluation of sarcopenia and adiposity revealed significant prognostic information. Visceral fat could also play an important role in response to CDK 4/6 inhibitors, deserving further investigation.