BackgroundImmune checkpoint inhibitors (ICI) can achieve durable responses in a subset of patients with locally advanced or metastatic urothelial carcinoma (aUC). The use of tumor genomic profiling ...in clinical practice may help suggest biomarkers to identify patients most likely to benefit from ICI.MethodsWe undertook a retrospective analysis of patients treated with an ICI for aUC at a large academic medical center. Patient clinical and histopathological variables were collected. Responses to treatment were assessed for all patients with at least one post-baseline scan or clear evidence of clinical progression following treatment start. Genomic profiling information was also collected for patients when available. Associations between patient clinical/genomic characteristics and objective response were assessed by logistic regression; associations between the characteristics and progression-free survival (PFS) and overall survival (OS) were examined by Cox regression. Multivariable analyses were performed to identify independent prognostic factors.ResultsWe identified 119 aUC patients treated with an ICI from December 2014 to January 2020. Genomic profiling was available for 78 patients. Overall response rate to ICI was 29%, and median OS (mOS) was 13.4 months. Favorable performance status at the start of therapy was associated with improved OS (HR 0.46, p=0.025) after accounting for other covariates. Similarly, the presence of a TERT promoter mutation was an independent predictor of improved PFS (HR 0.38, p=0.012) and OS (HR 0.32, p=0.037) among patients who had genomic profiling available. Patients with both a favorable performance status and a TERT promoter mutation had a particularly good prognosis with mOS of 21.1 months as compared with 7.5 months in all other patients (p=0.03).ConclusionsThe presence of a TERT promoter mutation was an independent predictor of improved OS in a cohort of aUC patients treated with an ICI who had genomic data available. Most of the clinical and laboratory variables previously shown to be prognostic in aUC patients treated with chemotherapy did not have prognostic value among patients treated with an ICI. Genomic profiling may provide important prognostic information and affect clinical decision making in this patient population. Validation of these findings in prospective patient cohorts is needed.
Background
There is increasing interest in non-desensitization protocols as a potential way to reintroduce chemotherapy following hypersensitivity reactions (HSR).
Objective
To provide insight into ...the potential utility of non-desensitization reintroduction, particularly at institutions where allergy consultation may not be available.
Methods
For 70 patients with platinum HSR who underwent rechallenge with standard (≤2 hours), extended (1-bag, 1-step, 4–6 hours), or titrated (4-to-5-bag and -step, 6–7.5 hours) infusions between 1/2014 and 7/2019, demographics and clinical characteristics were reviewed and initial and breakthrough reactions (BTR) were graded using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Tolerance (no BTR) and completion (dose completed despite BTR) were compared using Fisher's exact test.
Results
Patients (mean standard deviation age 57 13 years, initial HSR grade 2 1), were rechallenged with standard (n = 8), extended (n = 23), or titrated (n = 22) infusions after oxaliplatin HSR; and standard (n = 5) or titrated (n = 12) after carboplatin HSR. Tolerance and completion were higher for extended versus (vs) standard (tolerance-87%-vs-8%, p < 0.005; completion-96%-vs-38%, p < 0.005) and titrated versus standard (tolerance-76%-vs-8%, p < 0.005; completion-79%-vs-38%, p < 0.05) infusions.
Conclusions
Extended and titrated infusions may increase reintroduction safety compared to standard infusions. Further investigation into extended infusions may provide a safe alternative to standard infusions in patients who may not have access to desensitization at their institution.
322
Background: Bevacizumab-awwb and bevacizumab are vascular endothelial growth factor (VEGF) inhibitors that are commonly combined with other oncolytic agents for the treatment of various ...malignancies. Real-world outcomes and financial impact of biosimilar use are limited, particularly for oncologic indications. In patients with non-small cell lung cancer, bevacizumab-awwb and bevacizumab demonstrated similar clinical efficacy and safety. Bevacizumab-awwb outcomes in other cancer subtypes are lacking. The purpose of this study is to compare the safety and financial impact associated with the utilization of biosimilar bevacizumab-awwb vs bevacizumab. Methods: This is an IRB-approved, single-center, retrospective cohort study including adult cancer patients who were initiated on bevacizumab-awwb or bevacizumab between June 2019 and May 2021. Eligible patients for bevacizumab-awwb treatment must have been naïve to bevacizumab treatment. Patients switching from bevacizumab to bevacizumab-awwb or participating in clinical trials were excluded. Common Terminology Criteria for Adverse Events Version 5 was used for safety outcomes assessment. The primary safety outcome was new-onset, grade ≥ 2+ hypertension (HTN). The secondary safety outcomes include grade ≥ 2+ proteinuria, hemorrhage, and gastrointestinal perforation, and cost using the average wholesale price for drug acquisition. Results: In this study, 377 patients were included with 200 Bevacizumab and 177 Bevacizumab-awwb patients. There were 11 cancer types with similar baseline characteristics among both groups except for ovarian and hepatocellular carcinoma. Although there was no significant difference in grade ≥ 2+ HTN, initiation of new antihypertensive therapy was found to be greater in the bevacizumab arm (p = 0.002). Grade 2 proteinuria was observed to be lower in the Bevacizumab-awwb arm (p = 0.01). There were no significant differences in other safety outcomes. In 2020, bevacizumab-awwb utilization accounted for 34% of bevacizumab orders, saving $167,000. If bevacizumab-awwb utilization increased to 75%, approximately $400,000 can be saved per year. Conclusions: In this real-world analysis, bevacizumab-awwb demonstrated a comparable safety profile to bevacizumab in regards to grade ≥ 2+ hypertension, proteinuria, hemorrhage and gastrointestinal perforation regardless of primary cancer type. Replacing Bevacizumab for Bevacizumab-awwb lowered drug acquisition costs.
Abstract only
476
Background: Reliable predictive markers are lacking in patients (pts) with locally advanced or metastatic urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICI). ...We sought to determine whether specific genomic alterations could be used to predict overall survival (OS) in this patient population. Methods: We undertook a retrospective cohort study of pts with aUC who received ICI and underwent genomic profiling by next-generation sequencing (NGS). All patients underwent NGS using commercially available platforms (e.g. Foundation Medicine, Strata, Invitae), or testing on the CLIA-certified institutional panel UCSF500. Associations between the 20 most frequently altered genes and OS were first examined by Cox regression. Genes with a p <0.1 on univariate analysis and relevant clinical variables were then included in a multivariable analysis. Results: We identified 78 pts treated with ICI for aUC with available genomic profiling results. Median age at ICI initiation was 71; the majority of patients had visceral metastases (70.5%), ECOG performance status ≤1 (62.8%) and received ICI in the post-platinum setting (52.6%). Objective response rate in this cohort was 35.9%, median progression free survival was 4.0 months (95% CI 2.6-10.5) and median OS was 17.5 months (95% CI 14.1-NR) from ICI start. The most commonly altered genes were the TERT promoter (TERTp) (61%), TP53 (52%), RB1 (31%), CDKN2A(29%) and CDKN2B (27%). On univariable analysis there was a trend towards longer OS in pts with TERTp mutations (HR 0.53, 95% CI 0.27-1.06, p = 0.07), and shorter OS in pts with CDKN2B mutations (HR 1.91, 95% CI 0.98-3.73, p = 0.06). Both mutations were included in a multivariable analysis. After adjusting for known prognostic variables (ECOG PS, visceral metastases, albumin, hemoglobin, body mass index BMI, neutrophil to lymphocyte ratio NLR, and histology), the presence of a TERTp mutation was significantly associated with improved OS (HR 0.30, 95% CI 0.10-0.93, p = 0.04; Table). Conclusions: The presence of a TERTp mutation was an independent predictor of improved OS in a cohort of aUC pts treated with ICI. Other common mutations and clinical variables were not associated with OS on a multivariable analysis. These findings are hypothesis-generating and prospective validation is needed. Table: see text
Abstract only
502
Background: ICIs are effective agents in metastatic urothelial carcinoma in both platinum-refractory and frontline settings. Responses in patients (pts) with non-urothelial ...histological variants are not well defined. Methods: We undertook a retrospective analysis of pts with metastatic bladder cancer treated with ICI monotherapy. Pts were identified as having a variant histology if any non-urothelial component was present. Fisher’s exact test was used to assess differences in ORR by histology. Results: Between 12/2014 and 10/2019, 102 pts received ICI monotherapy, of whom 93 were evaluable for response and 33 had variant histology. Median age was 70 yrs, 66% were male, 50% received prior platinum-based chemotherapy. Most received pembrolizumab (66%) or atezolizumab (33%). ORR in the overall cohort was 26% (15% PR, 11% CR), with 12% having SD. Histology breakdown and responses are shown in Table. Although twice as many responses were seen in urothelial pts as in pts with variant histologies (ORR 31% vs 15%), this difference was non-significant (p = 0.14). Conclusions: In this large single-institution cohort, ORR in a heterogeneous population of bladder cancer pts was consistent with data previously reported in clinical trials. Pts with variant histologies had numerically lower responses relative to pure urothelial histology, but this difference was not statistically significant. Clinical benefit to ICIs was seen across multiple variant histologies suggesting potential efficacy in this patient population that should be confirmed prospectively.Table: see text
PDF
