Immune to immunotherapy.

Hormone receptor(+) breast cancer has notoriously low immunogenicity, resulting in quite lackluster responses to prior attempts with immune checkpoint inhibition (ICI). One thought is adding ICI to chemo may have a synergistic effect. Why? Chemo such as the microtubule inhibitor eribulin blunts the immunosuppressive effects of the TGF-β pathway. Plus a combo of chemo plus ICI has proven quite successful for triple-negative breast cancer. This phase 2 trial enrolled 88 women with HR(+), HER2(-) breast cancer refractory to 2+ lines of previous endocrine therapy and no more than 2 previous lines of chemo. All received eribulin, a common second-line chemo option for HR(+) breast cancer, and were randomized to +/- the addition of pembrolizumab. Unfortunately, the primary endpoint of progression-free survival was virtually identical and not very long (4 months). Neither was there a difference in objective response rate. TBL: We still haven’t seen a breakthrough for ICI in the treatment of HR(+) breast cancer.  | Tolaney, JAMA Oncol 2020

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