Y. Ruano (Madrid, Spain)
University Hospital 12 De OctubreAuthor Of 1 Presentation
- O. Martínez Saez (Barcelona, Spain)
- P. Tolosa (Madrid, Spain)
- A. Sánchez De Torre (Madrid, Spain)
- T. Pascual (bcn, Spain)
- F. Brasó-Maristany (Barcelona, Spain)
- A. Rodriguez Hernandez (Barcelona, Spain)
- L. Parrilla (Madrid, Spain)
- A. Roncero (Madrid, Spain)
- Y. Ruano (Madrid, Spain)
- N. Chic (Barcelona, Spain)
- F. Schettini (Barcelona, Spain)
- J. Laguna Montes (Barcelona, Spain)
- E. Sanfeliu Torres (Barcelona, Spain)
- B. Gonzalez-Farre (Barcelona, Spain)
- M. Vidal (Barcelona, Spain)
- B. Adamo (Barcelona, Spain)
- M. Guillén (Barcelona, Spain)
- M. Munoz (Barcelona, Spain)
- A. Prat (Barcelona, Spain)
- E. Ciruelos (Madrid, Spain)
23P - CDK4/6 inhibition and endocrine therapy (ET) in the HER2-enriched subtype (HER2-E) in hormone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer (ABC): a retrospective analysis of real-world data
Abstract
Background
The HER2-E subtype within HR+/HER2- ABC represents 10-25% and is characterized by poor prognosis. In the MONALEESA program, ribociclib + ET was found highly active in this subtype compared to ET. Here, we explored the prognostic and predictive value of HER2-E in patients (pts) treated with a CDK4/6 inhibitor (CDK4/6i) + ET in the real-world setting.
Methods
This is a retrospective study of 144 consecutive pts with HR+/HER2- ABC treated with a CDK4/6i + ET in the first line setting from 2014-2020 in Hospital 12 de Octubre (Madrid) and Clinic of Barcelona. Research-based PAM50 was performed in FFPE tumors collected before CDK4/6i (primary tumors or metastatic biopsies). Univariate and multivariable cox model progression-free survival (PFS) analyses were performed adjusting for the presence of visceral or “de novo” disease, menopausal status and performance status.
Results
114 pts (79%) had PAM50 data (50% primary/50% metastatic), and 47%/46%/7% received palbociclib/ribociclib/abemaciclib. Subtype distribution: Luminal A (33%), Luminal B (37%), HER2-E (19%), normal-like (8%) and Basal-like (5%). Median PFS for HER2-E disease was 7.4 months (mo) (95% confidence interval [CI] 5.0-22.0) and 21.1 mo (95% CI 16.6-31.3) for non-HER2-E disease (adjusted hazard ratio [aHRatio]=2.38, p=0.010). Median OS for HER2-E disease was 30.9 months (mo) (95% confidence interval [CI] 13.2-not reached [NR]) and NR (95% CI 47.2-NR) for non-HER2-E disease (aHRatio=4.39, p=0.021). Although exploratory and statistically non-significant, the PFS HRatio estimates of ribociclib vs palbociclib/abemaciclib in Luminal A, Luminal B and HER2-E subtype were 0.88, 0.90 and 0.44, respectively. Finally, the overall response rate of ribociclib in Luminal A/B and HER2-E disease was 40.5% and 42.9% vs 36.8% and 25.0% with palbociclib/abemaciclib.
Conclusions
In a real-world setting, we confirmed the poor prognosis of the HER2-E subtype in HR+/HER2- ABC. Despite the limitations, our results support the observation from the ML program where ribociclib in combination with ET was particularly active in the HER2-E subtype.
Legal entity responsible for the study
The authors.
Funding
Instituto de Salud Carlos III (PI19/01846) (to A.P.) Instituto 299 de Salud Carlos III (PI18/01408) (to E.C.) Breast Cancer Research Foundation (to 300 A.P.) PhD4MD (to N.C.) Fundació La Marató TV3 (to A.P) RESCUER Horizon 2020 301 (to A.P.) Save the Mama (to A.P.) Pas a Pas (to A.P.) Asociación Cáncer de Mama 302 Metastásico (to A.P.) Fundación Científica Asociación Española Contra el Cáncer (to 303 F.B.M.) Fundación SEOM (SEOM 2018 Grant: Fellowship for Training in 304 Research in Reference Centers) (to T.P.).
Disclosure
O. Martínez-Sáez: Advisory/Consultancy: Roche; Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: Eisai. P. Tolosa: Honoraria (institution), Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Eisai. T. Pascual: Advisory/Consultancy: Roche; Advisory/Consultancy: Genentech. N. Chic: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Pierre Fabre. J.C. Laguna: Speaker Bureau/Expert testimony: Kyowa Kirin. M. Vidal: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self): Daiichi Sankyo; Travel/Accommodation/Expenses: Pfizer. M. Muñoz: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Lilly; Speaker Bureau/Expert testimony: Pierre Fabre; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Eisai. A. Prat: Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Amgen; Honoraria (self), Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self): MSD Oncology; Advisory/Consultancy: NanoString Technologies; Honoraria (self): Lilly; Advisory/Consultancy: Pfizer. E.M. Ciruelos: Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.