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Multicenter Study
. 2025 Oct:83:104554.
doi: 10.1016/j.breast.2025.104554. Epub 2025 Aug 5.

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

Leandro Jonata de Carvalho Oliveira  1 , Daniela Dornelles Rosa  2 , Artur Katz  3 , Daniele Assad-Suzuki  4 , Daniel Argolo  5 , Solange Moraes Sanches  6 , Laura Testa  7 , José Bines  8 , Rafael Aliosha Kaliks  9 , Debora de Melo Gagliato  10 , Romualdo Barroso-Sousa  11 , Tatiana Strava Corrêa  4 , Andrea Kazumi Shimada  12 , Carlos Henrique Dos Anjos  12 , Rudinei Linck  3 , Thais Baccili Cury Megid  13 , Daniel Negrini Batista  14 , Daniel Musse Gomes  15 , Marcelle Goldner Cesca  6 , Débora Gaudêncio  16 , Larissa Matos Almeida Moura  16 , Julio Antonio Pereira de Araújo  17 , Renata Colombo Bonadio  7 , Zenaide Silva de Souza  18 , Juliana Rodrigues Beal  9 , Mario Machado Lopes  19 , Leticia Telles Sales  3 , Júlia Leal Franco Parisi Marlière  3 , Max Senna Mano  20
Affiliations
Multicenter Study

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

Leandro Jonata de Carvalho Oliveira et al. Breast. 2025 Oct.

Abstract

Background: In 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.

Methods: This 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.

Results: Among 922 patients, ODX showed low (<11), intermediate (11-25), and high (>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 relevance: HR+/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.

Keywords: Cyclin-dependent kinase 4 and 6 inhibitors; Genomic signatures; Hormone receptor positive early breast cancer; Oncotype DX; Real-world data.

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Conflict of interest statement

Declaration of competing interest LO has received honoraria from Fleury, unrelated to this work. LT has received honoraria from Novartis, Roche, Pfizer, Zodiac, Lilly, MSD, Daiichi Sankyo, AstraZeneca, and BeiGene; served on advisory boards for Lilly, Novartis, MSD, Daiichi Sankyo, AstraZeneca, Pfizer, and Roche; received educational support from Pfizer, Libbs, United Medical, Lilly, Zodiac, Daiichi Sankyo, Gilead, AstraZeneca, MSD, and Roche; and institutional research funding from Novartis, all unrelated to this work. JB has received honoraria and/or served on advisory boards for AstraZeneca, Daiichi Sankyo, Exact Sciences, Gilead Sciences, Knight, Libbs, Lilly, MSD, Novartis, Pfizer, and Roche; and received travel grants from AstraZeneca, Daiichi Sankyo, and Gilead, unrelated to this work. DMG has received honoraria from Lilly, Roche, AstraZeneca, Daiichi Sankyo/Lilly, Novartis, and Pfizer; served in advisory roles for Teva, Roche/Genentech, Lilly, Daiichi Sankyo/Lilly, and Pfizer; received research funding from Novartis; and travel support from AstraZeneca, Libbs, and Roche, all unrelated to this work. AKS has received speaker honoraria from Daiichi Sankyo/AstraZeneca, Novartis, Pfizer, Lilly, Gilead Sciences, Roche, and Libbs; served in advisory roles for Daiichi Sankyo/AstraZeneca and Pfizer; and received travel support from Novartis and Daiichi Sankyo/AstraZeneca, unrelated to this work. RCB has received speaker and/or consultancy honoraria from Daiichi Sankyo, Nestlé Health Science, Addium, Gilead, MSD, BMS, AstraZeneca, Aché, Pfizer, Novartis, and Lilly; received financial support for educational activities from AstraZeneca, Daiichi Sankyo, MSD, and Lilly; and institutional research support from Novartis and AstraZeneca, unrelated to this work. All other authors have declared no conflicts of interest.

Figures

Fig. 1
Fig. 1
Invasive disease-free survival (iDFS) and distant disease-free survival (DDFS) in patients eligible for abemaciclib and ribociclib and treated with endocrine therapy alone.
See this image and copyright information in PMC

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