Searching Beyond Programmed Cell Death Ligand 1 in Metastatic Breast Cancer—Still Haven’t Found What We’re Looking For
Mené sur 106 patientes atteintes d'un cancer du sein triple négatif de stade métastatique (âge moyen : 55 ans), cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de l'atézolizumab au carboplatine
Despite great advances in breast cancer outcomes during the last decade, the benefit of immune checkpoint inhibitors (ICIs) remains limited to a select population of patients with triple-negative breast cancer (TNBC). Monotherapy ICIs have a limited role in breast cancer, with only tissue-agnostic indications, but combination ICI with chemotherapy is more successful with indications in early and metastatic TNBC.In this issue of JAMA Oncology, Lehmann and colleagues report results from TBCRC 043, a phase 2 randomized clinical trial that evaluated the efficacy of carboplatin area under the curve 6 every 3 weeks with or without treatment with atezolizumab, 1200 mg, every 3 weeks in the first-line or second-line setting for 106 patients with metastatic TNBC (unselected for programmed death ligand 1 [PD-L1] status). The primary end point of progression-free survival (PFS) favored carboplatin plus atezolizumab, although it was not statistically significant (4.1 vs 2.2 months; P = .05). For the secondary end point, carboplatin plus atezolizumab was associated with statistically improved overall survival (12.6 vs 8.6 months; P = .03). Interestingly, in the subgroup analysis, PD-L1 positivity (SP142 > 1%) was not associated with greater benefit with carboplatin plus atezolizumab; rather, patients with PD-L1–negative tumors had greater benefit (although the numbers were small). Also, high tumor-infiltrating lymphocytes (TILs) and tumor mutation burden (TMB) high (TMB-H) were associated with a greater benefit from the combination. This trial raises important questions about the predictive value of current biomarkers for patients with TNBC.
JAMA Oncology , éditorial en libre accès, 2022