Liver Metastasis Is Associated with Poor Progression-Free Survival in Patients with Non–Small Cell Lung Cancer Treated with Nivolumab

Population Modeling of Tumor Kinetics and Overall Survival to Identify Prognostic and Predictive Biomarkers of Efficacy for Durvalumab in Patients With Urothelial Carcinoma

“…Our results suggest that liver metastasis is the most influential and statistically significant covariate for tumor growth. This finding is consistent with recent reports showing that liver metastasis is associated with poor prognosis in various cancers . We also showed that baseline tumor size and IC are the most influential and significant covariates for tumor killing after durvalumab treatment.…”

“…This finding is consistent with recent reports showing that liver metastasis is associated with poor prognosis in various cancers. [13][14][15][16][17] We also Figure 2 Forest plots of covariate effects on k g (a) and k kill (b) estimated from the full covariate tumor kinetic model and survival hazard (c) from the full covariate survival model. Circles represent the calculated percent change in the parameter value from the reference value at the indicated covariate values, using the point estimates of the respective covariate effects; error bars represent the 95% confidence intervals of the covariate effects based on the relative standard error estimates from NONMEM; dashed vertical lines represent the reference value; dotted lines represent the 30% change from reference value.…”

Tissue‐specific tumor microenvironments influence responses to immunotherapies

“…A recently revealed clinical trend shows some association with liver metastases and reduced responses to αPD‐1 across cancer types in melanoma, urothelial cancer, TNBC and NSCLC . However, there are some conflicting results with some studies reporting no associations with liver metastases .…”

“…Evidence has recently emerged for the tumor location influencing the response of human tumors to immunotherapies, particularly to αPD‐1 and αPD‐1/αCTLA4 . In particular, retrospective analysis has revealed reduced responses to checkpoint blockade in tumors in certain metastatic sites compared with primary tumors in melanoma, non‐small‐cell lung cancer (NSCLC), urothelial cancer and triple‐negative breast cancer (TNBC) . Due to the complexity of tumors at different anatomical sites, including tumor genetic heterogeneity, the tissue‐specific impact on therapy responses in human tumors is yet to be elucidated.…”

“…[10][11][12] In particular, retrospective analysis has revealed reduced responses to checkpoint blockade in tumors in certain metastatic sites compared with primary tumors in melanoma, non-small-cell lung cancer (NSCLC), urothelial cancer and triple-negative breast cancer (TNBC). 11,[13][14][15][16][17][18][19][20][21][22][23][24][25] Due to the complexity of tumors at different anatomical sites, including tumor genetic heterogeneity, the tissue-specific impact on therapy responses in human tumors is yet to be elucidated. Previously, we and others used genetically identical murine tumor lines to eliminate genetic heterogeneity and have shown differences in the TME composition and therapy responses of tumors growing in different anatomical sites in murine models of cancer.…”