Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
Role of ctDNA in Predicting the Outcome of Patients with Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer Treated with First-line Ribociclib and Letrozole: BioItaLEE Trial.
СтатьяКлиническое исследование III фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Bianchini Giampaolo, Malorni Luca, Caputo Roberta, Zambelli Alberto, Puglisi Fabio, Bianchi Giulia V, Del Mastro Lucia, Paris Ida, Montemurro Filippo, Colleoni Marco, Allegrini Giacomo, Tamberi Stefano, Zamagni Claudio, Cazzaniga Marina E, Orditura Michele, Guarneri Valentina, Adamo Vincenzo, Romagnoli Emanuela, Valerio Maria Rosaria, Cinieri Saverio, Benelli Matteo, Callari Maurizio, Valsecchi Diletta, Castelletti Daniela, Grasso Donatella, Fenderico Nicola, Arpino Grazia, De Laurentiis Michelino
Аннотация
PURPOSE: This phase IIIb study prospectively evaluated the prognostic and predictive value of baseline and dynamic circulating tumor DNA (ctDNA) in postmenopausal patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) treated with first-line ribociclib/letrozole.
EXPERIMENTAL DESIGN: A total of 287 patients were enrolled, with ctDNA analyzed at baseline (n = 263), day 15 of cycle 1 (C1D15; n = 238), C2D1 (n = 241), and first imaging (n = 206). The primary objective was to identify ctDNA alterations, characterize their evolution across treatment time points, and assess their association with progression-free survival (PFS).
RESULTS: Median PFS was 23.4 months (95% confidence interval, 20.8 to not estimable). At baseline, the most frequently altered genes were PIK3CA (22.1%) and TP53 (15.5%). Alterations in TP53, MYC, and HER- and cyclin-dependent kinase 4/6- pathway genes were linked to early progression. Absence of a detectable mutation at baseline (n = 150, 57%) was associated with a better prognosis [hazard ratio (HR) = 0.41]. Among patients with a detectable mutation at baseline (n = 104), early clearance (mutation undetectability) was observed in 47.1% at C1D15 and 52.4% at C2D1 and was associated with improved PFS (C1D15, HR = 0.51; C2D1, HR = 0.44). In patients without a detectable mutation at baseline, 22.7% (n = 34) developed new mutations at C1D15, C2D1, or first imaging. Patients without new mutations had a lower risk of progression (HR = 0.45).
CONCLUSIONS: Pretreatment and early dynamics of ctDNA represent promising prognostic and predictive biomarkers in patients with HR+/HER2- ABC treated with ribociclib/letrozole. Early ctDNA dynamics seem to be a promising surrogate biomarker for treatment. Further studies are warranted to validate their clinical utility.
EXPERIMENTAL DESIGN: A total of 287 patients were enrolled, with ctDNA analyzed at baseline (n = 263), day 15 of cycle 1 (C1D15; n = 238), C2D1 (n = 241), and first imaging (n = 206). The primary objective was to identify ctDNA alterations, characterize their evolution across treatment time points, and assess their association with progression-free survival (PFS).
RESULTS: Median PFS was 23.4 months (95% confidence interval, 20.8 to not estimable). At baseline, the most frequently altered genes were PIK3CA (22.1%) and TP53 (15.5%). Alterations in TP53, MYC, and HER- and cyclin-dependent kinase 4/6- pathway genes were linked to early progression. Absence of a detectable mutation at baseline (n = 150, 57%) was associated with a better prognosis [hazard ratio (HR) = 0.41]. Among patients with a detectable mutation at baseline (n = 104), early clearance (mutation undetectability) was observed in 47.1% at C1D15 and 52.4% at C2D1 and was associated with improved PFS (C1D15, HR = 0.51; C2D1, HR = 0.44). In patients without a detectable mutation at baseline, 22.7% (n = 34) developed new mutations at C1D15, C2D1, or first imaging. Patients without new mutations had a lower risk of progression (HR = 0.45).
CONCLUSIONS: Pretreatment and early dynamics of ctDNA represent promising prognostic and predictive biomarkers in patients with HR+/HER2- ABC treated with ribociclib/letrozole. Early ctDNA dynamics seem to be a promising surrogate biomarker for treatment. Further studies are warranted to validate their clinical utility.