Six-year absolute invasive disease-free survival benefit of adding adjuvant pertuzumab to trastuzumab and chemotherapy for patients with early HER2-positive breast cancer: A Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of the APHINITY (BIG 4-11) trial
- Author(s)
- Gelber, RD; Wang, XV; Cole, BF; Cameron, D; Cardoso, F; Tjan-Heijnen, V; Krop, I; Loi, S; Salgado, R; Kiermaier, A; Frank, E; Fumagalli, D; Caballero, C; de Azambuja, E; Procter, M; Clark, E; Restuccia, E; Heeson, S; Bines, J; Loibl, S; Piccart-Gebhart, M; APHINITY Steering Committee and Investigators;
- Journal Title
- European Journal of Cancer
- Publication Type
- Research article
- Abstract
- AIM: The APHINITY trial showed that adding adjuvant pertuzumab (P) to trastuzumab and chemotherapy, compared with adding placebo (Pla), significantly improved invasive disease-free survival (IDFS) for patients with HER2+ early breast cancer both overall and for the node-positive (N+) cohort. We explored whether adding P could benefit some N- subpopulations and whether to consider de-escalation for some N+ subpopulations. METHODS: Subpopulation Treatment Effect Pattern Plot (STEPP) is an exploratory, graphical method that plots estimates of treatment effect for overlapping patient subpopulations defined by a covariate of interest. We used STEPP to estimate Kaplan-Meier differences in 6-year IDFS percentages (P minus Pla: Delta +/- standard error [SE]), both overall and by nodal status, for overlapping subpopulations defined by (1) a clinical composite risk score, (2) tumour infiltrating lymphocytes (TILs) percentage, and (3) human epidermal growth factor receptor 2 (HER2) FISH copy number. Because of multiplicity, a Delta of at least three SE is required to warrant attention. RESULTS: The average absolute gains in 6-year IDFS percentages were 2.8 +/- 0.9 overall; 4.5 +/- 1.2 for N+ and 0.1 +/- 1.1 for N-. Largest gains were for patients with intermediate clinical composite risk (5.3 +/- 1.9 overall; 6.9 +/- 2.3 N+; 4.0 +/- 3.0 N-), highest TILs percentage (6.3 +/- 1.7 overall; 7.4 +/- 2.4 N+; 3.2 +/- 1.7 N-), and intermediate HER2 copy number (2.8 +/- 1.9 overall; 7.4 +/- 2.5 N+; -1.3 +/- 1.9 N-), but clear evidence indicating a pattern of differential subpopulation treatment effects was lacking. CONCLUSIONS: STEPP plots for N- did not identify subpopulations clearly benefiting from adding P, and those for N+ did not identify subpopulations warranting de-escalation. TILs percentage appeared to be more predictive of P treatment effect than clinical composite risk score. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT01358877.
- Keywords
- Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; *Breast Neoplasms/pathology; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Humans; Receptor, ErbB-2/metabolism; Trastuzumab; Treatment Outcome; Adjuvant therapy; HER2-positive early breast cancer; Pertuzumab; STEPP (Subpopulation Treatment Effect Pattern Plot); TILs (tumour infiltrating lymphocytes)
- Department(s)
- Medical Oncology; Laboratory Research
- PubMed ID
- 35313167
- Publisher's Version
- https://doi.org/10.1016/j.ejca.2022.01.031
- Open Access at Publisher's Site
https://doi.org/10.1016/j.ejca.2022.01.031- Terms of Use/Rights Notice
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Creation Date: 2024-10-25 06:46:54
Last Modified: 2024-10-25 06:48:14