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Observational Study
. 2025 Feb 25:217:115219.
doi: 10.1016/j.ejca.2024.115219. Epub 2025 Jan 3.

Efficacy outcomes of CDK4/6 inhibitors in combination with endocrine therapy treatment in hormone receptor-positive/HER2-negative advanced breast cancer according to PAM50 intrinsic subtype: Primary results of SOLTI-1801 CDK-PREDICT study

Pablo Tolosa  1 , Tomás Pascual  2 , Olga Martínez-Saez  3 , Cristina Hernando  4 , Sonia Servitja  5 , María Fernández Abad  6 , Fara Brasó-Maristany  3 , Ester Sanfeliu  7 , Javier David Benitez Fuentes  8 , Laura Lema  9 , Yolanda Ruano  10 , Isabel García-Fructuoso  3 , Lucía Parrilla  11 , Adela Rodríguez  3 , Ana María Roncero  9 , María Ángeles Cobos  9 , Rodrigo Sánchez-Bayona  12 , Manuel Alva  9 , Ainhoa Madariaga  9 , Guillermo Villacampa  13 , Jordi Canes  13 , Fernando Salvador  13 , Agustín Sánchez-Belmonte  14 , Marcos Malumbres  15 , Aleix Prat  2 , Eva Ciruelos  16
Affiliations
Observational Study

Efficacy outcomes of CDK4/6 inhibitors in combination with endocrine therapy treatment in hormone receptor-positive/HER2-negative advanced breast cancer according to PAM50 intrinsic subtype: Primary results of SOLTI-1801 CDK-PREDICT study

Pablo Tolosa et al. Eur J Cancer. .

Abstract

Introduction: The prognostic value of PAM50 intrinsic subtypes (IS), cell cycle, and immune-related gene expression in HR+ /HER2- advanced breast cancer (BC) treated with CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) in a first-line metastatic setting is unclear. This study evaluates these biomarkers in metastatic biopsies from patients diagnosed with HR+ /HER2- advanced BC.

Methods: CDK-PREDICT study is a multicentric, ambispective observational cohort study conducted in six Spanish hospitals. It included patients diagnosed with HR+ /HER2- advanced BC treated in the first-line setting with CDK4/6i and ET. Baseline biopsies were obtained prior to treatment to determine research-based PAM50 IS, cell cycle and immune-related gene expression. The primary objective was to evaluate progression-free survival (PFS) differences among PAM50 IS using uni- and multivariable Cox regression models. Secondary objectives included overall survival (OS), overall response rate (ORR), and correlating cell cycle and immune response gene expression with PFS.

Results: A total of 185 patients were included, with a median follow-up of 38.5 months. PAM50 luminal subtypes were predominant (82.7 %). Non-luminal subtypes showed significantly shorter median PFS (10.2 vs. 25.7 months; HR, 2.50; p < 0.001) and OS (32.3 vs. 58.1 months; HR, 2.54; p < 0.001) than luminal subtypes. Higher cell cycle and immune-related genes expression, such as CCNE1 and PDCD1, as well as tumor infiltrating lymphocytes were associated with poorer outcomes.

Conclusions: This study confirms the independent prognostic value of PAM50 IS in HR+ /HER2- advanced BC treated with CDK4/6i and ET. Non-luminal subtypes exhibited the worst prognosis, underscoring the need for novel therapeutic strategies in this population.

Keywords: Biomarkers; CDK 4/6 inhibitors; Gene expression; Hormone receptor-positive/HER2-negative advanced breast cancer; Intrinsic subtypes; PAM50.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Declaration of Interest: P.T. reports advisory and consulting fees from AstraZeneca, Daiichi-Sankyo, Adamed, Novartis, Pfizer, Lilly, Esteve, Gilead, Roche and Reveal Genomics. T.P. reports advisory and consulting fees or speaker honoraria from Novartis, Astra Zeneca, Lilly, Pfizer, Veracyte, Gilead, and Roche, and support for attending meetings and/or travel from Gilead. O.M-S reports advisory/consulting fees from Reveal Genomics, Roche, and Astrazeneca, lecture fees from Daiichi Sankyo, Novartis, Pfizer and Eisai and travel expenses from Gilead and Novartis. F.B-M. reports patents filed: PCT/EP2022/086493, PCT/EP2023/060810, EP23382703 and EP23383369, and part time employment by Reveal Genomics. I.G-F: Reports invited speaker fees from Novartis, Daiichi-Sankyo, and Eisai; advisory/consulting fees from Novartis; and travel expenses from Novartis, Gilead, and Lilly. R.S-B reports advisory/consulting/speaker fees from Roche, AstraZeneca, Novartis, Lilly, Daiichi Sankyo, Pfizer, Eisai, GlaxoSmithKline, Reveal Genomics, and Gilead; travel expenses from Pfizer, AstraZeneca, Gilead, Novartis, and Roche. A.M. reports honoraria from AstraZeneca, Clovis, GSK, PharmaMar, Immunogen, Pharma&, Immunogen. F.S. has been employed by AstraZeneca since June 2024, however involvement in this study predates this employment and AstraZeneca had no involvement in the studyA.P. reports advisory and consulting fees from AstraZeneca, Roche, Pfizer, Novartis, Daiichi Sankyo, Ona Therapeutics, and Peptomyc, lecture fees from AstraZeneca, Roche, Novartis, and Daiichi Sankyo, institutional financial interests from AstraZeneca, Novartis, Roche, and Daiichi Sankyo; stockholder and employee of Reveal Genomics; patents filed PCT/EP2016/080056, PCT/EP2022/086493, PCT/EP2023/060810, EP23382703 and EP23383369. E.C. reports advisory/consulting/speaker fees from Roche, AstraZeneca, Novartis, Lilly, Daiichi Sankyo, Pfizer, and Gilead; travel expenses from Pfizer, AstraZeneca, MSD, Novartis, and Roche. All remaining authors have declared no conflicts of interest.

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