CDK4 and metastatic neoplasm: In addition, a recent pooled analysis evaluating five registration trials for CDK4/6 inhibitors led by the FDA concluded that all patients benefited from the addition of CDK4/6 inhibitor to endocrine therapy, including patients with de novo metastatic disease, bone-only metastasis, or patients whose tumors were negative for progesterone receptor in immunohistochemistry [45].