Cancer outcomes in patients eligible for adjuvant cyclin-dependent kinase 4 and 6 inhibitors but spared adjuvant chemotherapy by Oncotype Dx: A multicenter retrospective GBECAM 0520 study.

BackgroundIn pivotal CDK4/6 inhibitor (CDK4/6i) adjuvant trials, most patients received chemotherapy (CT). However, the role of CDK4/6i in patients spared CT by a genomic signature remains unclear. We investigated the proportion of patients without genomic CT indication but eligible for adjuvant abemaciclib or ribociclib, and estimated their potential benefit from CDK4/6i.MethodsThis retrospective, real-world study included patients with T1-T3, N0-N1, HR+/HER2- early breast cancer (eBC) who underwent Oncotype DX (ODX) testing (2005-2024) at nine Brazilian institutions. Genomic CT indication followed TAILORx and RxPONDER; CDK4/6i eligibility followed MonarchE and NATALEE. Primary endpoints were 5-year invasive disease-free survival (iDFS) and distant disease-free survival (DDFS) among patients eligible for CDK4/6i, without genomic CT indication, treated with endocrine therapy (ET) alone.ResultsAmong 922 patients, ODX showed low (25) genomic risk in 170 (18.4 %), 585 (63.5 %), and 167 (18.1 %), respectively. Overall, 24 (2.6 %) and 120 (13 %) were eligible for abemaciclib and ribociclib, respectively, had no CT indication, and received ET alone. In these patients (median follow-up: 57.8 and 66.4 months), 5-year iDFS and DDFS were 100 %.Conclusions and relevanceHR+/HER2- eBC patients eligible for CDK4/6i but spared CT by ODX are a minority and have excellent outcomes with ET alone. This highlights the potential benefits of integrating genomic and clinical risk stratification to refine therapeutic decision-making regarding the need for CDK4/6i.