Biomarker Analyses in the Phase 3 ASCENT Study of Sacituzumab Govitecan Versus Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer
Menée auprès de 468 patientes atteintes d'un cancer du sein triple négatif métastatique réfractaire ou ayant évolué après deux chimiothérapies, cet essai de phase III évalue l'efficacité, du point de vue du taux de réponse objective, de la survie sans maladie et de la survie globale, du sacituzumab govitécan en fonction de l'expression tumorale de Trop-2 et de la présence de mutations constitutionnelles BRCA1/2
Background : The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-Trop-2 antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy of physician’s choice (TPC) in previously-treated metastatic triple-negative breast cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes. Patients and methods : Patients with mTNBC refractory to or progressing after
≥
2 prior chemotherapies, with
≥
1 in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (either capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine Trop-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline. Results : Of 468 evaluable patients, 290 had Trop-2 expression data (64% [n=151 SG] versus 60% [n=139 TPC] and 292 had known BRCA1/2 mutation status (63% [n=149 SG] versus 61% [n=143 TPC]). Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for high, medium, and low Trop-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38% and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low Trop-2 expression. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations. Conclusions : SG benefits patients with previously treated mTNBC expressing high/medium Trop-2 compared with standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low Trop-2 expression precludes definitive conclusions on the benefit of SG in this subgroup.