Cancer outcomes from a real-world cohort of patients eligible for adjuvant CDK4/6 inhibitors but without genomic risk for chemotherapy: A GBECAM multicenter retrospective study.

540 Background: In the MonarchE and Natalee studies, most patients received (neo)adjuvant chemotherapy (CT). In the precision oncology era, genomic signatures such as Oncotype DX (ODX) can spare many patients of CT. Our recent Real-World data (RWD) showed that a proportion of patients with hormone receptor positive (HR+) HER2 negative (HER2-) early breast cancer (eBC) would be eligible for adjuvant abemaciclib or ribociclib without genomic indication for CT. The main question addressed in this analysis is the potential benefit of adjuvant CDK4/6i in the non-CT eligible population; for this, we evaluated cancer recurrence outcomes of these patients. Methods: This is a multicentric RWD study derived from a large dataset of patients with T1-T3, N0-N1, HR+/HER2- eBC who had an ODX performed between 2005 and 2020 and were treated across nine Brazilian institutions. Projections of CT indication by genomic criteria were based on TAILORx and RxPONDER data. Projections of adjuvant CDK4/6i indication were based on the MonarchE and Natalee inclusion criteria. Primary endpoints were 4-year invasive disease-free survival (4-yr iDFS) and 4-year distant disease-free survival (4-yr DDFS) rates in the cohort of patients potentially eligible for CDK4/6i without genomic indication for CT and who did not receive adjuvant CT in the clinical practice. Results: Of 636 patients, the ODX indicated low (25) genomic risk in 117 (18.4%), 408 (64.1%) and 111 (17.5%) patients, respectively. 408 patients (64.2%) had low clinical risk and 228 patients (35.8%) had high clinical risk disease. In the overall cohort, 12 (1.8%) and 67 (10.5%) pts were eligible for adjuvant abemaciclib and ribociclib, respectively, without having received adjuvant CT (both by genomic indication and clinical practice). In patients with indication of abemaciclib (median follow-up FU of 23 months; a maximum of 114 months), 4-yr iDFS and 4-yr DDFS rates were both 100%. In patients with indication of ribociclib (median follow-up of 33 months; a maximum of 127 months), 4-yr iDFS and 4-yr DDFS rates were both 100%. In the entire cohort, there was only one distant recurrence event, at 96 months after diagnosis, in a 55-year-old patient with stage IIB (T2N1) eBC and low genomic risk (RS=11). Conclusions: In times of rapid incorporation of both GES and adjuvant CDK4/6i, our results suggest that patients eligible for adjuvant abemaciclib and/or ribociclib in the non-CT population have a favorable short-term outcome with endocrine therapy alone. Therefore, additional data and longer follow-up are needed to clarify the role of these costly and potentially toxic agents in patients spared CT by genomic signatures.