The authors collected patient data from the clinico-genomic database (CGDB), which contains electronic health records and genomic data from 800 sites of care in the United States. They identified 386 patients who met the eligibility criteria. Among these, 118 patients received front-line immune checkpoint inhibitors, while 268 received front-line chemotherapy. Data on PD-L1 status – a commonly used biomarker – was lacking in 75% of patients. Other biomarkers reported previously, such as the presence of specific mutations and median tumor mutational burden, were similar between the two groups. Median overall survival was 5.4 months in the immune checkpoint inhibitor group and 8.2 months in the chemotherapy group.
High tumor mutational burden was associated with increased overall survival in the immune checkpoint inhibitor group but not in the chemotherapy group. Importantly, in chemotherapy- treated patients, those with high APOBEC mutational signatures significantly had worse OS (HR, 1.43; 95% CI, 1.06–1.94; P=0.02).
Next, Szabados et al. derived a model with four variables associated with higher overall survival in the immune checkpoint inhibitors: non-metastatic disease at initial diagnosis, normal albumin levels, previous surgery for organ-confined disease, and high TMB. These variables were then used to develop a bladder immune performance index. A higher index score was associated with longer overall survival in the immune checkpoint inhibitor group.
This study employed a novel approach for identifying biomarkers and developing a bladder immune performance index score in the context of immune checkpoint inhibitor treatment in patients with metastatic urothelial cancer. Including real-world populations of patients from the clinico-genomic database increases the generalizability of the data. The association between higher APOBEC-induced mutational load and lower survival with chemotherapy is consistent with the role of APOBEC-induced mutations in other tumor types. One limitation is the potential heterogeneity in differences in treatment regimens and procedures across different healthcare institutions.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
References:
- Szabados B, Ponz-Sarvisé M, Machado R, et al. Clinico-Genomic Characterization of Patients with Metastatic Urothelial Carcinoma in Real-World Practice Identifies a Novel Bladder Immune Performance Index (BIPI). Clin Cancer Res. 2022;28(18):4083-4091. doi:10.1158/1078-0432.CCR-22-0200