Breast
Julia Tchou, MD PhD
Professor
University of Pennsylvannia
Wayne, Pennsylvania, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Immune checkpoint inhibition (ICI) is currently only used in combination with chemotherapy in breast cancer since ICI alone is ineffective. It is unclear if non-chemotherapy strategies, such as radiation therapy (RT) specifically targeting the tumor may improve ICI effectiveness through immune-stimulatory effects. To test this hypothesis, we initiated a phase 1b/2 trial to evaluate the feasibility and efficacy of preop pembrolizumab (ICI) +/- a tumor-directed RT fraction (7 Gy) in patients with eBC.
Methods:
Inclusion criteria of this open-label trial (3 treatment arms) are as depicted in Figure. Arms 1 & 2 differ by the treatment order of preop RT and ICI. In arm 3, patients receive preop ICI alone. In Phase 1b, patients are assigned 1:1 into Arms 1 & 2 according to tumor subtype. In Phase 2, patients are assigned (1:1:1) into arms 1, 2, & 3 according to tumor subtype. Standard of care surgery occurs on day 21 after enrollment (day 0). Standard adjuvant systemic therapy +/- RT follows as recommended by treating oncologists.
Results:
The study was initiated in January, 2021. Phase 1b was completed and feasibility established in June 2021. Thus far, 9 patients (7 TNBC, 1 HR+HER2- and 1 HER2+) have enrolled. Of the 7 patients with TNBC, tumor shrinkage was observed In 4 patients (57%). Exceptional pathologic response, defined as < 10% viable tumor, was noted in 2 patients with near complete pathologic response (pCR) reminiscent of the histologic changes (tumor necrosis/fibrosis in residual tumor bed) seen with pCR after neoadjuvant chemotherapy (NAC).
Conclusions:
Preop ICI+RT may achieve near pCR in some patients with e-BC. Samples collected at various timepoints in this study will help elucidate mechanisms and biomarkers to identify strategies to improve pCR rate and to predict response a priori. Our results may lead to a larger study in which chemotherapy omission, i.e, treatment de-escalation, may be feasible in select patients with near pCR after preop ICI+RT.