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Retrospective Analysis of Mortality Cases in Advanced and Metastatic Solid Tumors With Concurrent Prerenal Azotemia.

ABSTRACT: BACKGROUND/AIM:A retrospective study of cases with metastatic or advanced solid tumors complicated with AKI (acute kidney injury) with prerenal azotemia. PATIENTS AND METHODS:Criteria included: (1) advanced or metastatic solid tumors that led to mortality; (2) prerenal azotemia identified upon renal function evaluation and (3) BUN to Cr ratio (BCR)?15. We also compared the outcomes of patients with BCR>20 with those of patients with BCR=15-20. RESULTS:A total of 218 patients with solid tumors were enrolled. One hundred and forty (64%) and 78 (36%) patients had BCR>20 and 15-20, respectively. Before AKI occurrence, 136 (62%) had thromboembolic complications and 96 (44%) paraneoplastic syndromes. Median survival time was 1 week in all patients. Median survival time was statistically different between the groups with BCR15-20 and BCR>20 (p<0.005, log-rank test). CONCLUSION:Cancer patients with concurrent AKI and prerenal azotemia carry a very poor prognosis.

SUBMITTER: Liao TY

PROVIDER: S-EPMC7279785 | biostudies-literature | 2020 May-Jun

REPOSITORIES: biostudies-literature

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Retrospective Analysis of Mortality Cases in Advanced and Metastatic Solid Tumors With Concurrent Prerenal Azotemia.

Liao Tzu-Yao TY Liaw Chuang-Chi CC

In vivo (Athens, Greece) 20200501 3

<h4>Background/aim</h4>A retrospective study of cases with metastatic or advanced solid tumors complicated with AKI (acute kidney injury) with prerenal azotemia.<h4>Patients and methods</h4>Criteria included: (1) advanced or metastatic solid tumors that led to mortality; (2) prerenal azotemia identified upon renal function evaluation and (3) BUN to Cr ratio (BCR)≥15. We also compared the outcomes of patients with BCR>20 with those of patients with BCR=15-20.<h4>Results</h4>A total of 218 patient ...[more]

PMID: 32354956

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Project description:BackgroundSeveral studies have evaluated the relationship between tumor mutational burden (TMB) and outcomes of immune checkpoint inhibitors. In the phase II KEYNOTE-158 study of pembrolizumab monotherapy for previously treated recurrent or metastatic cancer, high TMB as assessed by the FoundationOne CDx was associated with an improved objective response rate (ORR).MethodsWe retrospectively assessed the relationship between TMB and efficacy in participants with previously treated advanced solid tumors enrolled in 12 trials that evaluated pembrolizumab monotherapy, including 3 randomized trials that compared pembrolizumab with chemotherapy. TMB was assessed in formalin-fixed, paraffin-embedded pretreatment tumor samples by whole-exome sequencing. High TMB was defined as ≥175 mutations/exome. Microsatellite instability (MSI) phenotype was based on whole-exome sequencing results. Programmed death ligand 1 (PD-L1) expression was assessed by immunohistochemistry. The primary end point was ORR assessed per RECIST V.1.1 by independent central review. Other end points included progression-free survival (PFS) assessed per RECIST V.1.1 by independent central review and overall survival (OS).ResultsOf the 2234 participants in the analysis, 1772 received pembrolizumab monotherapy and 462 received chemotherapy. Among the pembrolizumab-treated participants, ORR was 31.4% (95% CI 27.1 to 36.0) in the 433 participants with TMB ≥175 mutations/exome and 9.5% (95% CI 8.0 to 11.2) in the 1339 participants with TMB <175 mutations/exome. The association of TMB with ORR was observed regardless of PD-L1 expression and not driven by specific tumor types or participants with very high TMB or high MSI. In the 3 randomized controlled trials, TMB was associated with ORR (p≤0.016), PFS (p≤0.005), and OS (p≤0.029) of pembrolizumab but not of chemotherapy (p≥0.340, p≥0.643, and p≥0.174, respectively), and pembrolizumab improved efficacy versus chemotherapy in participants with TMB ≥175 mutations/exome.ConclusionsTMB ≥175 mutations/exome is associated with clinically meaningful improvement in the efficacy of pembrolizumab monotherapy and improved outcomes for pembrolizumab versus chemotherapy across a wide range of previously treated advanced solid tumor types. These data suggest TMB has broad clinical utility irrespective of tumor type, PD-L1 expression, or MSI status and support its use as a predictive biomarker for pembrolizumab monotherapy in participants with previously treated advanced solid tumors.

Dataset Information

Retrospective Analysis of Mortality Cases in Advanced and Metastatic Solid Tumors With Concurrent Prerenal Azotemia.

Publications

Retrospective Analysis of Mortality Cases in Advanced and Metastatic Solid Tumors With Concurrent Prerenal Azotemia.

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