American Association for Cancer Research
Browse

Figure S2 from A Prognostic Model Based on PAM50 and Clinical Variables (PAM50MET) for Metastatic Hormone Receptor–positive HER2-negative Breast Cancer

Download (237.24 kB)
figure
posted on 2023-03-31, 22:08 authored by Aleix Prat, Yi-Hsuan Tsai, Tomás Pascual, Laia Paré, Barbara Adamo, Maria Vidal, Fara Brasó-Maristany, Patricia Galván, Jan Christoph Brase, Vanessa Rodrik-Outmezguine, Stephen Johnston, Eva Ciruelos, Joel S. Parker

Survival outcomes based on the PAM50MET score in the EGF30008 trial. (A) Progression-free survival using a predefined cutoff in patients treated with placebo. (B) Progression-free survival using a predefined cutoff in patients treated with lapatinib. (C) Overall survival using a predefined cutoff in patients treated with placebo. (D) Overall survival using a predefined cutoff in patients treated with lapatinib. Interaction tests between PAM50 and treatment arm for PFS and OS were statistically non-significant (all p-values >0.05). PAM50MET, final model.

Funding

Instituto de Salud Carlos III

Breast Cancer Research Foundation

Breast Cancer Now

European Union's Horizon 2020 and innovation programme

Fundació la Maratóde TV3

History

ARTICLE ABSTRACT

Predicting prognosis in HR+/HER2− metastatic breast cancer (MBC) might be clinically useful; however, no validated prognostic biomarkers exist in this setting to date. In phase III, EGF30008 trial, 484 patients with HER2− MBC who received letrozole and placebo or lapatinib were selected. PAM50 data, ECOG performance status, visceral disease, number of metastasis, biopsy type, and age were evaluated. A progression-free survival (PFS) Cox model was evaluated. The final model (PAM50MET) with a prespecified cutoff was validated in patients (n = 261) with HR+/HER2− advanced breast cancer (aBC) from BOLERO-2 (phase III trial that evaluated exemestane and placebo or everolimus). In EGF30008, prognostic models with PAM50 plus clinical variables yielded higher C-index values versus models with only PAM50 or clinical variables. The PAM50MET model combined 21 variables: 2 PAM50 subtypes, basal signature, 14 genes, and 4 clinical variables. In EGF30008, the optimized cutoff was associated with PFS [HR = 0.37; 95% confidence interval (CI), 0.29–0.47; P < 0.0001] and overall survival (OS; HR = 0.37; 95% CI, 0.27–0.51; P < 0.0001). The median (months; 95% CI) PFS and OS were 22.24 (19.0–24.9) and not reached in PAM50MET-low versus 9.13 (8.15–11.0) and 33.0 (28.0–40.0) in PAM50MET-high groups, respectively. In BOLERO-2, the PAM50MET-low was associated with better PFS (HR = 0.72; 95% CI, 0.53–0.96; P = 0.028) and OS (HR = 0.51; 95% CI, 0.35–0.69; P < 0.0001). The median (months) (95% CI) PFS and OS were 6.93 (5.57–11.0) and 36.9 (33.4–NA) in PAM50MET-low versus 5.23 (4.2–6.8) and 23.5 (20.2–28.3) in PAM50MET-high groups, respectively. PAM50MET is prognostic in HR+/HER2− MBC, and further evaluation might help identify candidates for endocrine therapy only or novel therapies.

Usage metrics

    Clinical Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC