Discussion
tumor, sarcomas, sarcoma, well-differentiated/dedifferentiated liposarcoma, rhabdomyosarcoma, tumors
TUMOR, SARCOMAS, SARCOMA, PROLIFERATIVE, RHABDOMYOSARCOMA, EWING SARCOMA, AMPLIFICATION, TUMORS, ARREST
This phase II trial met its primary endpoint of 6-month PFSR with 6 out of 21 evaluable patients (29%) achieving a PFS longer than 6 months. This outcome was obtained in a wide range of histological sarcoma subtypes, with the only exclusions being well-differentiated/dedifferentiated liposarcoma (WD/DD-LPS), rhabdomyosarcoma and Ewing sarcoma. The median PFS of 4.2 months and OS of 12 months reached for patients with progressing tumors at baseline and having been heavily pretreated, with a median of 3 previous systemic therapeutic lines, is encouraging. This outcome seems favorable to a real-life setting, where in a similar pretreated subset of sarcoma patients the time to next treatment, which can be equated with PFS, ranged from 2.3 to 3.7 months and the OS ranged from 5.4 to 8.5 months.The most recognized consequence of CDK4/6 inhibition is RB-dependent proliferative arrest. Palbociclib prevents the phosphorylation of the Rb protein and, as a result, prevents its inactivation. As expected, this cytostatic effect would attain tumor stabilization at best with uncommon tumor responses. The proportion of stabilizations detected (62%) also favorably compares with the clinical benefit rate reported in third (less than 50%) or further lines (<25%) in advanced STS.Patient selection by high mRNA expression of Besides, the unplanned posterior mutation screening for Amplification of CDK4 is one molecular hallmark of WD/DD-LPS and is the reason why palbociclib was tested in this specific sarcoma subtype. In two different studies that enrolled 29 and 60 evaluable advanced WD/DD-LPS patients, palbociclib was prescribed at 200 mg per day, 2 weeks on and one week off, and 125 mg per day, 3 weeks on and 1 week off, respectively.In recent times, several works have emphasized the relevance of the p16-CDK4/6-RB1 pathway in sarcomas. Alteration of the The lack of The study offered RNA analysis for Despite the fact that a valuable predictive biomarker selection for CDK4/6 inhibition is challenging, the selected biomarkers with RNA overexpression of Future therapeutic strategies combining CDK4/6 inhibitors with other compounds seem worthwhile and also deserve to be explored in the sarcoma field. The synergy between CDK4/6 inhibitors and estrogen receptor (ER) antagonists in blocking ERThe findings from this single-arm, phase II trial suggest that palbociclib has activity in advanced sarcomas other than WD/DD-LPS selected by RNA expression of 