Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Clin Cancer Res ; 27(5): 1391-1398, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33262136

ABSTRACT

PURPOSE: Circulating tumor cells (CTC) are under investigation as a minimally invasive liquid biopsy that may improve risk stratification and treatment selection. CTCs uniquely allow for digital pathology of individual malignant cell morphology and marker expression. We compared CTC features and T-cell counts with survival endpoints in a cohort of patients with metastatic genitourinary cancer treated with combination immunotherapy. EXPERIMENTAL DESIGN: Markers evaluated included pan-CK/CD45/PD-L1/DAPI for CTCs and CD4/CD8/Ki-67/DAPI for T cells. ANOVA was used to compare CTC burden and T-cell populations across timepoints. Differences in survival and disease progression were evaluated using the maximum log-rank test. RESULTS: From December 2016 to January 2019, 183 samples from 81 patients were tested. CTCs were found in 75% of patients at baseline. CTC burden was associated with shorter overall survival (OS) at baseline (P = 0.022), but not on-therapy. Five morphologic subtypes were detected, and the presence of two specific subtypes with unique cellular features at baseline and on-therapy was associated with worse OS (0.9-2.3 vs. 28.2 months; P < 0.0001-0.013). Increasing CTC heterogeneity on-therapy had a trend toward worse OS (P = 0.045). PD-L1+ CTCs on-therapy were associated with worse OS (P < 0.01, cycle 2). Low baseline and on-therapy CD4/CD8 counts were also associated with poor OS and response category. CONCLUSIONS: Shorter survival may be associated with high CTC counts at baseline, presence of specific CTC morphologic subtypes, PD-L1+ CTCs, and low %CD4/8 T cells in patients with metastatic genitourinary cancer. A future study is warranted to validate the prognostic utility of CTC heterogeneity and detection of specific CTC morphologies.


Subject(s)
Biomarkers, Tumor/analysis , Immunotherapy/methods , Neoplastic Cells, Circulating/pathology , T-Lymphocytes/immunology , Urogenital Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Metastasis , Prognosis , Retrospective Studies , Survival Rate , T-Lymphocytes/classification , Urogenital Neoplasms/immunology , Urogenital Neoplasms/therapy , Young Adult
2.
J Clin Oncol ; 38(31): 3672-3684, 2020 11 01.
Article in English | MEDLINE | ID: mdl-32915679

ABSTRACT

PURPOSE: We assessed the safety and efficacy of cabozantinib and nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignances. PATIENTS AND METHODS: Patients received escalating doses of CaboNivo or CaboNivoIpi. The primary objective was to establish a recommended phase II dose (RP2D). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), duration of response (DoR), and overall survival (OS). RESULTS: Fifty-four patients were enrolled at eight dose levels with a median follow-up time of 44.6 months; data cutoff was January 20, 2020. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 75% and 87% of patients treated with CaboNivo and CaboNivoIpi, respectively, and included fatigue (17% and 10%, respectively), diarrhea (4% and 7%, respectively), and hypertension (21% and 10%, respectively); grade 3 or 4 immune-related AEs included hepatitis (0% and 13%, respectively) and colitis (0% and 7%, respectively). The RP2D was cabozantinib 40 mg/d plus nivolumab 3 mg/kg for CaboNivo and cabozantinib 40 mg/d, nivolumab 3 mg/kg, and ipilimumab 1 mg/kg for CaboNivoIpi. ORR was 30.6% (95% CI, 20.0% to 47.5%) for all patients and 38.5% (95% CI, 13.9% to 68.4%) for patients with mUC. Median DoR was 21.0 months (95% CI, 5.4 to 24.1 months) for all patients and not reached for patients with mUC. Median PFS was 5.1 months (95% CI, 3.5 to 6.9 months) for all patients and 12.8 months (95% CI, 1.8 to 24.1 months) for patients with mUC. Median OS was 12.6 months (95% CI, 6.9 to 18.8 months) for all patients and 25.4 months (95% CI, 5.7 to 41.6 months) for patients with mUC. CONCLUSION: CaboNivo and CaboNivoIpi demonstrated manageable toxicities with durable responses and encouraging survival in patients with mUC and other GU tumors. Multiple phase II and III trials are ongoing for these combinations.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Urogenital Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Anilides/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , B7-H1 Antigen/metabolism , Carcinoma, Transitional Cell/secondary , Colitis/chemically induced , Diarrhea/chemically induced , Epithelial Cell Adhesion Molecule/metabolism , Fatigue/chemically induced , Female , Hepatitis/etiology , Humans , Hypertension/chemically induced , Ipilimumab/administration & dosage , Male , Middle Aged , Neoplastic Cells, Circulating/metabolism , Nivolumab/administration & dosage , Progression-Free Survival , Proto-Oncogene Proteins c-met/metabolism , Pyridines/administration & dosage , Receptors, CXCR4/metabolism , Response Evaluation Criteria in Solid Tumors , Survival Rate , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...