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Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer

par Bardia, Aditya;Tolaney, Sara S.M.;Punie, Kevin;Loirat, Delphine;Oliveira, Mafalda;Kalinsky, Kevin;Zelnak, Amelia A.B.;Aftimos, Philippe ;Dalenc, Florence;Sardesai, Sagar S.D.;Hamilton, Erika;Sharma, Priyanka;Recalde, Sabela;Gil, E.C.;Traina, Tiffany T.A.;O'Shaughnessy, Joyce;Cortes, Javier;Tsai, Meng Han;Vahdat, Linda L.T.;Diéras, Veronique;Carey, Lisa L.A.;Rugo, Hope H.S.;Goldenberg, David D.M.;Hong, Quang QT;Olivo, Martin M.S.;Itri, Loretta Marie;Hurvitz, Sara
Référence Annals of oncology
Publication Publié, 2021

Article révisé par les pairs

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Résumé :

Background: The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment 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 two or more prior chemotherapies, with one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (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 assessable 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, respectively. 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.