Atezolizumab and nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study
Menée sur 902 patientes atteintes d'un cancer du sein triple négatif, cette étude analyse, dans le cadre d'un essai de phase III évaluant le nab-paclitaxel en combinaison avec l'atézolizumab, l'association entre des biomarqueurs de la réponse immunitaire (niveau d'expression de PD-L1 sur les cellules immunitaires et les cellules tumorales, le niveau d'expression intratumorale de CD8 et la quantité de lymphocytes ayant infiltré le stroma tumoral), la présence d'altérations au niveau des gènes BRCA1/2 et la survie sans progression ainsi que la survie globale
Background: Understanding the impact of the tumor immune microenvironment and BRCA-related DNA repair deficiencies on the clinical activity of immune checkpoint inhibitors may help optimize both patient and treatment selection in metastatic triple-negative breast cancer (mTNBC). In this substudy from the phase 3 IMpassion130 trial, immune biomarkers and BRCA alterations were evaluated for association with clinical benefit with atezolizumab (A) + nab-paclitaxel (nP) vs placebo + nP in unresectable locally advanced or mTNBC.
Methods: Patients were randomized 1:1 to nab-paclitaxel 100 mg/m2 (days 1, 8, and 15 of a 28-day cycle) + atezolizumab 840 mg every 2 weeks or placebo until progression or toxicity. Progression-free survival (PFS) and overall survival (OS) were evaluated based on programmed death-ligand 1 (PD-L1) expression on immune cells (IC) and tumor cells (TC), intratumoral CD8, stromal tumor-infiltrating lymphocytes (sTILs), and BRCA1/2 mutations.
Results: PD-L1 IC+ in either primary or metastatic tumor tissue was linked to PFS and OS benefit with A+nP. PD-L1 IC+ low (26.9%; 243 of 902 patients) and high (13.9%; 125 of 902 patients) populations had improved outcomes that were comparable. Intratumoral CD8 and sTILs positivity were associated with PD-L1 IC+ status; A+nP vs P+nP improved outcomes were observed only in CD8+ and sTIL+ patients who were also PD-L1 IC+. BRCA1/2 mutations (occurring in 14.5% [89 of 612 patients]) were not associated with PD-L1 IC status, and PD-L1 IC+ patients benefited from A+nP regardless of BRCA1/2 mutation status.
Conclusions: Although A+nP was more efficacious in patients with richer tumor immune microenvironment, clinical benefit was only observed in patients whose tumors were PD-L1 IC+.S
Journal of the National Cancer Institute , article en libre accès, 2020