Tumor infiltrating lymphocytes as a predictor of adjuvant avelumab efficacy in patients with high-risk triple negative breast cancer

PURPOSE: We aimed to investigate the prognostic and predictive value of tumor infiltrating lymphocytes (TILs) for adjuvant immunotherapy in high-risk early TNBC. PATIENTS AND METHODS: The phase III A-BRAVE trial randomized 466 patients with high-risk early TNBC to adjuvant avelumab or observation after standard therapy. Inclusion criteria allowed two strata: Stratum A (primary surgery followed by adjuvant chemotherapy, defined at high risk based on pathological stage) and Stratum B (neoadjuvant chemotherapy followed by surgery without pathological complete response). TILs were centrally assessed on treatment-naive tumor samples (BSL-TILs) and on residual disease after neoadjuvant chemotherapy (RD-TILs, Stratum B). Residual cancer burden (RCB) was assessed in Stratum B. Survival endpoints were: disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). RESULTS: BSL-TILs were available for 387 patients, RD-TILs for 330 patients (290 with both BSL-TILs and RD-TILs). Higher BSL-TILs were independently associated with improved outcomes across all endpoints. In Stratum B, higher RD-TILs showed a significant independent association with improved outcomes, outperforming BSL-TILs. RCB was also independently prognostic. Avelumab improved outcomes only for patients with BSL-TILs ≥30%, particularly in Stratum B (3-yr DDFS rates 92.0% vs 58.7%, HR 0.20 in high BSL-TILs and 70.4% vs 70.1%, HR 0.92 in low BSL-TILs, interaction p=0.019). Similar results for DFS and OS. RCB was not predictive for avelumab benefit. CONCLUSIONS: TILs may predict benefit from adjuvant immunotherapy in early TNBC. These findings warrant validation and support TILs-guided immunotherapy strategies in future trials. TRIAL REGISTRATION: NCT02926196.

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Journal
Clinical Cancer Research
Published
2026-07-17
DOI
https://doi.org/10.1158/1078-0432.ccr-26-0975
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
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article

Tumor infiltrating lymphocytes as a predictor of adjuvant avelumab efficacy in patients with high-risk triple negative breast cancer

Donata Sartori, Stefano Tamberi, Filippo Giovanardi, Daniele Generali et al.
Clinical Cancer Research
Cancer Immunotherapy and Biomarkers
article

Tumor infiltrating lymphocytes as a predictor of adjuvant avelumab efficacy in patients with high-risk triple negative breast cancer

Donata Sartori, Stefano Tamberi, Filippo Giovanardi, Daniele Generali, Giulia Bianchi, C. Zamagni, Michelino De Laurentiis, Gian Luca De Salvo, Fable Zustovich, Alberto Zambelli, Valentina Guarneri, Grazia Arpino, Pierfranco Conté, Alessandra Gennari, Adolfo Favaretto, Tommaso Giarratano, Peter Schmid, Antonino Musolino, Simon Spazzapan, Marta Mion, Lucia Del Mastro, Alessandra Emiliani, Maria Vittoria Dieci, Lorenzo Nicolè, Elisa Gasparini, Federico Piacentini, Antonella Ferro, Katia Cagossi, Saverio Cinieri
article en

Abstract

PURPOSE: We aimed to investigate the prognostic and predictive value of tumor infiltrating lymphocytes (TILs) for adjuvant immunotherapy in high-risk early TNBC. PATIENTS AND METHODS: The phase III A-BRAVE trial randomized 466 patients with high-risk early TNBC to adjuvant avelumab or observation after standard therapy. Inclusion criteria allowed two strata: Stratum A (primary surgery followed by adjuvant chemotherapy, defined at high risk based on pathological stage) and Stratum B (neoadjuvant chemotherapy followed by surgery without pathological complete response). TILs were centrally assessed on treatment-naive tumor samples (BSL-TILs) and on residual disease after neoadjuvant chemotherapy (RD-TILs, Stratum B). Residual cancer burden (RCB) was assessed in Stratum B. Survival endpoints were: disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). RESULTS: BSL-TILs were available for 387 patients, RD-TILs for 330 patients (290 with both BSL-TILs and RD-TILs). Higher BSL-TILs were independently associated with improved outcomes across all endpoints. In Stratum B, higher RD-TILs showed a significant independent association with improved outcomes, outperforming BSL-TILs. RCB was also independently prognostic. Avelumab improved outcomes only for patients with BSL-TILs ≥30%, particularly in Stratum B (3-yr DDFS rates 92.0% vs 58.7%, HR 0.20 in high BSL-TILs and 70.4% vs 70.1%, HR 0.92 in low BSL-TILs, interaction p=0.019). Similar results for DFS and OS. RCB was not predictive for avelumab benefit. CONCLUSIONS: TILs may predict benefit from adjuvant immunotherapy in early TNBC. These findings warrant validation and support TILs-guided immunotherapy strategies in future trials. TRIAL REGISTRATION: NCT02926196.

Clinical Cancer Research
University of Modena and Reggio Emilia (IT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), University of Padua (IT), University of Trieste (IT), Queen Mary University of London (GB), Barts Health NHS Trust (GB), Ospedale Santa Chiara (IT), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), Ospedale "Santa Maria delle Croci" di Ravenna (IT), Istituto Ramazzini (IT), AULSS 2 Marca Trevigiana (IT), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT), Ospedale A. Perrino (IT), Ospedale Papa Giovanni XXIII (IT), Istituto Oncologico Veneto (IT), Teccampos (Brazil) (BR), Azienda USL di Bologna (IT), Centro di Riferimento Oncologico (IT), Oncoceutics (United States) (US), Ospedale di Mirano (IT), Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), Istituti Ospitalieri di Cremona (IT), University of Naples Federico II (IT), University of Genoa (IT), Sapienza University of Rome (IT)
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Openalex Percentile: Top 11%
Cancer Immunotherapy and Biomarkers
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