Impact of age on clinical outcomes and efficacy of adjuvant dual anti-HER2 targeted therapy
Menée à partir de données portant sur 4 804 patientes atteintes d'un cancer du sein HER2+ de stade précoce et incluses dans un essai de phase III évaluant l'ajout du pertuzumab à un traitement combinant chimiothérapie adjuvante et trastuzumab, cette étude évalue l'association entre l'âge des patientes au diagnostic et la survie sans maladie invasive
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 (≤40 years and >40 years) was assessed. A STEPP analysis was conducted to illustrate possible treatment-effect heterogeneity based on age as a continuous factor.
Results : Out of 4,804 included patients, 768 (16.0%) were ≤40 years at enrollment. Median follow-up was 74 months (IQR 62–75 months). Young age was not prognostic either as dichotomous (HR 1.06; 95% CI 0.84–1.33) or continuous (HR 1.00; 95% CI 1.00–1.01) variable. Lack of prognostic effect of age was observed irrespective of hormone receptor status and treatment arm. No significant interaction was observed between age and pertuzumab effect (Pinteraction=0.605). Adding pertuzumab improved IDFS for both patients in the young (HR 0.86; 95% CI 0.56–1.32) and older (HR 0.75; 95% CI 0.62–0.92) cohorts. Similar results were observed irrespective of hormone receptor status. STEPP 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.
Journal of the National Cancer Institute , article en libre accès, 2021