Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
Tumor-Infiltrating Lymphocytes as a Predictor of Adjuvant Avelumab Efficacy in Patients with High-risk Triple-Negative Breast Cancer.
СтатьяКлиническое исследование III фазыРандомизированное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Dieci Maria Vittoria, Gasparini Elisa, Nicolé Lorenzo, Schmid Peter, Zambelli Alberto, Favaretto Adolfo, Piacentini Federico, Bianchi Giulia Valeria, Mion Marta, Ferro Antonella, Arpino Grazia, Emiliani Alessandra, Cinieri Saverio, Zamagni Claudio, Gennari Alessandra, Spazzapan Simon, Sartori Donata, Zustovich Fable, Tamberi Stefano, Del Mastro Lucia, de Laurentiis Michelino, Musolino Antonino, Cagossi Katia, Generali Daniele, Giarratano Tommaso, Giovanardi Filippo, De Salvo Gian Luca, Conte Pierfranco, Guarneri Valentina
Аннотация
PURPOSE: We aimed to investigate the prognostic and predictive value of tumor-infiltrating lymphocytes (TIL) for adjuvant immunotherapy in high-risk early triple-negative breast cancer (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 2 strata: stratum A (primary surgery followed by adjuvant chemotherapy, defined at high risk based on pathologic stage) and stratum B (neoadjuvant chemotherapy followed by surgery without pathologic complete response). TILs were centrally assessed on treatment-naïve tumor samples [baseline TILs (BSL-TIL)] and on residual disease (RD) after neoadjuvant chemotherapy (RD-TILs, stratum B). Residual cancer burden (RCB) was assessed in stratum B. Survival endpoints were disease-free survival (DFS), distant DFS (DDFS), and overall survival (OS).
RESULTS: BSL-TILs were available for 387 patients and 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-year DDFS rates, 92% 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 were obtained 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 TIL-guided immunotherapy strategies in future trials.
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 2 strata: stratum A (primary surgery followed by adjuvant chemotherapy, defined at high risk based on pathologic stage) and stratum B (neoadjuvant chemotherapy followed by surgery without pathologic complete response). TILs were centrally assessed on treatment-naïve tumor samples [baseline TILs (BSL-TIL)] and on residual disease (RD) after neoadjuvant chemotherapy (RD-TILs, stratum B). Residual cancer burden (RCB) was assessed in stratum B. Survival endpoints were disease-free survival (DFS), distant DFS (DDFS), and overall survival (OS).
RESULTS: BSL-TILs were available for 387 patients and 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-year DDFS rates, 92% 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 were obtained 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 TIL-guided immunotherapy strategies in future trials.