The primary analysis of the randomized, double-blind, placebo-controlled APHINITY trial included 4804 patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. With a median follow-up of 45.4 months, the study showed that adjuvant pertuzumab when added to trastuzumab and chemotherapy, significantly improved invasive disease-free survival compared with placebo in overall and node-positive disease.
An updated descriptive analyses of invasive disease-free survival with a median follow-up of 74.1 months demonstrated sustained benefit of adding pertuzumab both overall (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.64-0.91), and for node-positive disease (HR, 0.72; 95% CI, 0.59-0.87); notably, confidence intervals remained wide for the node-negative cohort (HR, 1.02; 95% CI, 0.69-1.53). Based on these significant overall effects, Richard D. Gelber of the Dana-Farber Cancer Institute, Boston, MA, and colleagues began to translate these findings into a study of absolute treatment benefits for specific subpopulations of patients.
The investigators used an exploratory, graphical technique that plots approximations of treatment effect for overlapping patient subpopulations defined by a covariate of interest called Subpopulation Treatment Effect Pattern Plot (STEPP).
The clinical composite risk score for invasive disease-free survival was calculated based on the overall cohort following the clinical characteristics of age, tumor size, number of positive nodes, and hormone receptor status. Scaled between 0 and 100, the composite risk scores with higher scores reflected a higher risk of an invasive disease-free survival event. For example, low clinical risk factors are T1N0 and age 40 to 64 years; high risk would be T3N2 or higher, and age ≥65 years and <40 years.
The composite risk of an invasive disease-free survival event did not depend on hormone receptor status at 74.1 months of median follow-up.
To approximate treatment effect for each subpopulation, differences of 6-year invasive disease-free survival were analyzed.
Based on the percent of patients with 6-year invasive disease-free survival in overall and node-negative and node-positive cohorts, the intermediate clinical composite risk subpopulation and the highest tumor-infiltrating lymphocyte percentages showed the largest absolute advances in 6-year invasive disease-free survival for pertuzumab compared with placebo.
Source: Gelber RD, Wang XV, Cole BF, et al. 6-year absolute invasive disease-free survival (IDFS) benefit of adding adjuvant pertuzumab to trastuzumab and chemotherapy for patients with early HER2-positive breast cancer: a STEPP analysis of the APHINITY (BIG 4-11) trial. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PS10-01.