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

Overview

Journal J Natl Cancer Inst

Publisher Oxford University Press

Specialty Oncology

Date 2022 May 5

PMID 35512402

Authors

Matteo Lambertini

Shona Fielding

Sibylle Loibl

Wolfgang Janni

Emma Clark

Maria Alice Franzoi

Debora Fumagalli

Carmela Caballero

Luca Arecco

Sharon Salomoni

Noam F Ponde

Francesca Poggio

Hee Jeong Kim

Cynthia Villarreal-Garza

Olivia Pagani

Shani Paluch-Shimon

Alberto Ballestrero

Lucia Del Mastro

Martine Piccart

Jose Bines

Ann H Partridge

Evandro de Azambuja

Affiliations

Soon will be listed here.

Abstract

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 (Pinteraction = 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.

Citing Articles

Subtype-Specific Survival of Young Women with Breast Cancer and Its Interaction with the Germline BRCA Status.

Hage A, Gebert P, Blohmer J, Hedayati E, Speiser D, Karsten M Cancers (Basel). 2024; 16(4).

PMID: 38398129 PMC: 10887122. DOI: 10.3390/cancers16040738.

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