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Impact of Age on Clinical Outcomes and Efficacy of Adjuvant Dual Anti-HER2 Targeted Therapy

BACKGROUND: Young age at breast cancer (BC) diagnosis has historically been a rationale for overtreatment. Limited data with short follow-up exist on the prognostic value of age at diagnosis in HER2-positive BC and the benefit of anti-HER2 therapy in young patients. METHODS: APHINITY (NCT01358877) i...

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Detalles Bibliográficos
Autores principales: Lambertini, Matteo, Fielding, Shona, Loibl, Sibylle, Janni, Wolfgang, Clark, Emma, Franzoi, Maria Alice, Fumagalli, Debora, Caballero, Carmela, Arecco, Luca, Salomoni, Sharon, Ponde, Noam F, Poggio, Francesca, Kim, Hee Jeong, Villarreal-Garza, Cynthia, Pagani, Olivia, Paluch-Shimon, Shani, Ballestrero, Alberto, Del Mastro, Lucia, Piccart, Martine, Bines, Jose, Partridge, Ann H, de Azambuja, Evandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360461/
https://www.ncbi.nlm.nih.gov/pubmed/35512402
http://dx.doi.org/10.1093/jnci/djac096
Descripción
Sumario:BACKGROUND: Young age at breast cancer (BC) diagnosis has historically been a rationale for overtreatment. Limited data with short follow-up exist on the prognostic value of age at diagnosis in HER2-positive BC and the benefit of anti-HER2 therapy in young patients. METHODS: APHINITY (NCT01358877) is an international, placebo-controlled, double-blind randomized phase III trial in HER2-positive early BC patients investigating the addition of pertuzumab to adjuvant chemotherapy plus trastuzumab. The prognostic and predictive value of age on invasive disease-free survival (IDFS) as continuous and dichotomous variable (aged 40 years or younger and older than 40 years) was assessed. A subpopulation treatment effect pattern plot analysis was conducted to illustrate possible treatment-effect heterogeneity based on age as a continuous factor. RESULTS: Of 4804 included patients, 768 (16.0%) were aged 40 years or younger at enrollment. Median follow-up was 74 (interquartile range = 62-75) months. Young age was not prognostic either as dichotomous (hazard ratio [HR] = 1.06, 95% confidence interval [CI] = 0.84 to 1.33) or continuous (HR = 1.00, 95% CI = 1.00 to 1.01) variable. Lack of prognostic effect of age was observed irrespective of hormone receptor status and treatment arm. No statistically significant interaction was observed between age and pertuzumab effect (P(interaction) = 0.61). Adding pertuzumab improved IDFS for patients in the young (HR = 0.86, 95% CI = 0.56 to 1.32) and older (HR = 0.75, 95% CI = 0.62 to 0.92) cohorts. Similar results were observed irrespective of hormone receptor status. Subpopulation treatment effect pattern plot analysis confirmed the benefit of pertuzumab in 6-year IDFS across age subpopulations. CONCLUSIONS: In patients with HER2-positive early BC treated with modern anticancer therapies, young age did not demonstrate either prognostic or predictive value, irrespective of hormone receptor status.