Abstract P2-10-26: Adjuvant pembrolizumab and chemotherapy or surveillance in Early Triple Negative breAst cancer with high stromal tumor-infiltrating lymphocytes (sTILs) score (ETNA)

Field: Medicine (Health Sciences)

Abstract Background: Several studies have shown that patients with stage I TNBC derive limited, if any, benefit from chemotherapy. sTILs, a surrogate marker for an active adaptive antitumor immune response, are strongly prognostic and predictive in patients with TNBC across all treatment settings. A recent individual patient-data meta-analysis has shown optimal survival outcomes in patients with stage I TNBC and sTIL ≥ 50% who did not undergo (neo)adjuvant systemic therapy, with a linear association between sTILs and prognosis [Leon Ferré et al, JAMA 2024]. Trial Design: ETNA trial (NCT06078384) is a phase II, open-label, international, multicenter, biomarker-driven study designed to evaluate chemotherapy de-escalation in patients with T1b/c N0M0 TNBC (ER/PgR &lt; 10% by IHC) and sTILs ≥ 30% in resected primary tumors. Eligible patients who have undergone adequate breast cancer surgery will be included in one of two cohorts based on their sTILs levels, as determined by a central review of the surgical specimen. Cohort 1 will include patients aged &gt; 40 years with 30% ≤ sTILs &lt; 50% and those aged ≤ 40 years with 30% ≤ sTILs &lt; 75%. Patients will receive 9 cycles of adjuvant pembrolizumab 200 mg every three weeks and Paclitaxel 80 mg/m2 weekly for 12 doses. Cohort 2 will include patients aged &gt; 40 years with sTILs ≥ 50% and those aged ≤ 40 years with sTILs ≥ 75%, who will undergo standard surveillance without adjuvant systemic treatment. A total of 1728 pT1b/cN0M0 TNBC patients will be screened for inclusion. Based on the TNBC pooled analysis [Leon Ferré et al, JAMA 2024] and the prevalence of young patients &lt; 40 years in the stage I TNBC population of CANTO (10%), we expect 12.5% of screened patients to be eligible for cohort 1 and 8% for cohort 2. The study will enroll 216 patients in cohort 1 and 138 patients in cohort 2. The primary endpoint is 5-year distant disease-free survival in the 2 cohorts. Secondary endpoints include 5-year invasive disease-free survival, distant recurrence-free survival and overall survival, safety analysis, and quality of life evaluations. Cohorts 1 and 2 will be analyzed independently. Ancillary studies will be performed on the surgical and blood samples to explore prognostic biomarkers and obtain a comprehensive description of TILs in patients with early-stage TNBC. Site activation is currently ongoing. Citation Format: Elie Rassy, Stefan Michiels, Magali Lacroix-Triki, Roberto Salgado, Paolo Nuciforo, Fatima Zohra Toumi, Jérôme Lemonnier, Juan Manuel Ferrero-Cafiero, Vittoria Barberi, Susana Muñoz, Isabel Pimentel, Esther Zamora, Maria Borrell, Oliver Tredan, Sophie Pellegrino, Fabrice André, Mafalda Oliveira, Barbara Pistilli. Adjuvant pembrolizumab and chemotherapy or surveillance in Early Triple Negative breAst cancer with high stromal tumor-infiltrating lymphocytes (sTILs) score (ETNA) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-10-26.