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Association details:
Evidence:
Evidence Level:
Sensitive: D – Preclinical
New
Title:

Targeting the ERß/HER Oncogenic Network in KRAS Mutant Lung Cancer Modulates the Tumor Microenvironment and Is Synergistic with Sequential Immunotherapy

Published date:
12/22/2021
Excerpt:
We evaluated the effects of fulvestrant and dacomitinib on murine bone marrow-derived macrophages (BMDMs) and CD8+ T cells, and tested the efficacy of the combination in vivo, using the KRAS mutant syngeneic lung adenocarcinoma model, FVBW-17….Concomitant administration of anti-PD-1 antibody with fulvestrant and dacomitinib was more efficacious than fulvestrant plus dacomitinib alone. Administering anti-PD-1 sequentially after fulvestrant plus dacomitinib was synergistic, with a two-fold greater tumor inhibitory effect compared to concomitant therapy, in both the flank model and in a lung metastasis model....Triple therapy provided significantly better growth inhibition than single agents or any of the dual therapy groups, with the sequential approach being the most effective regimen (Figure 5A)....F+anti-PD-1 showed a response rate of 60% (3 of 5), while D+anti-PD-1 had the same response rate as anti-PD-1 alone (20% [1 of 5]). For both triple therapy groups, the response rate was 100%.
Secondary therapy:
fulvestrant + anti-PD-1 antibody
DOI:
https://doi.org/10.3390/ijms23010081