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Background: Despite the widespread use of immune checkpoint inhibitors (ICIs), patterns of disease progression (POD) are poorly characterized. We aim to define these characteristics ...in patients (pts) with advanced urothelial carcinoma (UC) and renal cell carcinoma (RCC) treated with ICIs. Methods: We retrospectively reviewed charts of pts with advanced UC and RCC who received at least 2 ICI doses at our institution from 12/1/10 – 10/31/18. Demographics, medical history, ICI course, toxicity, and outcomes were recorded. Characteristics at the time of radiographic POD including location of metastases (mets), symptoms (sx), and hospitalization details were collected. Fisher’s exact test was used to study differences in pts with and without hospitalization at POD. Results: Of the 71 pts identified (UC N=53; RCC N=18), 59 pts had POD. At POD, 19 (32.2%) pts had new sites of disease involvement, while the remaining pts (N=40, 67.8%) had progression only at previously known sites of disease. Fourty-six (78.0%) pts had sx at POD: 1 sx (N=19, 32.2%), 2 sx (N=13, 22.0%), 3+ sx (N=14, 23.7%). Pain was the most common sx at POD (N=32, 54.2%), followed by loss of energy (N=18, 30.5%), and loss of appetite (N=14, 23.7%). Twenty-five (42.4%) pts were hospitalized at POD, most commonly for sepsis (N=8, 32%). No clinical factors were identified to predict for pts being hospitalized at POD. Conclusions: In our review of GU cancer patients on ICIs, a large proportion of pts reported clinical sx at POD, pain being the most frequent. Furthermore, a substantial number of pts were hospitalized at POD, most commonly for sepsis. Thus, further studies are warranted to confirm these findings, and potentially identify strategies to optimize patients’ quality-of-life and reduce rates of hospitalizations at the time of POD on ICIs.
Current first line treatment options in patients with metastatic urothelial carcinoma unfit to receive cisplatin containing chemotherapy include PD-1/L1 inhibitors and carboplatin containing ...chemotherapy. However, the optimal sequencing of these therapies remains unclear.
We conducted a multicenter retrospective analysis. Consecutive cisplatin ineligible patients with metastatic urothelial carcinoma treated with first line carboplatin containing chemotherapy followed sequentially by second line PD-1/L1 inhibitor, or the reverse order, were included. Patient demographics, objective response, time to treatment failure for first line and second line therapy, interval between end of first line and initiation of second line treatment (Interval
) and overall survival were collected. Multivariate analysis was conducted to examine the association of sequencing on overall survival.
In this multicenter retrospective study we identified 146 cisplatin ineligible patients with metastatic urothelial carcinoma treated with first line PD-1/L1 inhibitor therapy followed by second line carboplatin containing chemotherapy (group 1, 43) or the reverse sequence (group 2, 103). In the overall cohort median age was 72, 76% were men and 18% had liver metastasis. In both groups objective response rates were higher with carboplatin containing chemotherapy (45.6% first line, 44.2% second line) compared to PD-1/L1 inhibitors (9.3% first line, 21.3% second line). On multivariate analysis treatment sequence was not associated with overall survival (HR 1.05, p=0.85). Site of metastasis was the only factor significantly associated with overall survival (p=0.002).
In this biomarker unselected cohort of cisplatin ineligible patients with metastatic urothelial carcinoma, PD-1/L1 inhibitor followed by carboplatin containing chemotherapy and the reverse sequence had comparable overall survival.
Circulating tumor DNA (ctDNA) status before cystectomy can be used as a prognostic marker for disease recurrence and can predict lymph node involvement and locally advanced disease. Incorporation of ...ctDNA into clinical practice could help in guiding treatment intensification or deintensification.
Decision-making on the use of neoadjuvant and adjuvant treatment for patients with bladder cancer undergoing radical cystectomy (RC) currently depends on assessment of clinical and pathological features, which lack sensitivity. Circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. Our aim was to assess whether ctDNA status before RC is predictive of pathological and oncological outcomes. We also evaluated the dynamic changes in ctDNA status after RC in relation to recurrence-free survival (RFS).
We analyzed data for patients who underwent RC during 2021–2023 for whom prospective tumor-informed ctDNA analyses were conducted before and after RC. RFS was evaluated using the Kaplan-Meier method. Predictors for disease recurrence were assessed using Cox proportional-hazards models. Pathological outcomes associated with detectable ctDNA before RC were assessed in univariable and multivariable regression analyses.
We included 112 patients in the analysis. Median follow-up was 8 mo (interquartile range 4–13). ctDNA was detected before RC in 59 patients (53%) and was associated with poor RFS (log-rank p < 0.0001). Detectable ctDNA before RC was associated with poor outcomes regardless of clinical stage (<cT2 vs ≥cT2) and receipt of neoadjuvant therapy. Multivariable analyses revealed that detectable ctDNA before RC was associated with a higher risk of nodal disease (odds ratio 5.4, 95% confidence interval CI 1.9–18.2; p = 0.003) and locally advanced disease (odds ratio 3.6, 95% CI 1.5–9; p = 0.005). Cox regression analyses showed that detectable ctDNA before RC (hazard ratio 4.5, 95% CI 1–19; p = 0.04) and detectable ctDNA at the minimal residual disease window (hazard ratio 9.9, 95% CI 2.6–37; p < 0.001) were predictive of disease recurrence.
Detectable ctDNA before definitive therapy with RC is predictive of nodal involvement, locally advanced disease, and disease recurrence in patients with bladder cancer. ctDNA status holds promise for improving clinical staging and augmenting current decision-making tools.
We found that for patients with bladder cancer undergoing radical cystectomy, a test to show the presence of tumor DNA in blood before surgery was able to predict the risk of disease relapse and adverse pathology. Use of this assay could help in decision-making by clinicians and patients for optimal personalized treatment of this disease.
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Background: Anti-PD-1/PD-L1 agents and carbo-based chemo are therapy options in 1st-line (1L) setting for cisplatin-ineligible pts with mUC. However, optimal sequencing is unclear. ...Methods: We conducted a multicenter retrospective analysis of cisplatin-ineligible pts with mUC treated with 1L PD-1/PD-L1 monotherapy followed by carbo-based chemo (IO→Cb) or the reverse order (Cb→IO) without intervening systemic therapy. Perioperative cisplatin-based chemo was allowed if completed > 1 year from 1L mUC therapy initiation. To assess association between overall survival (OS) and therapy sequence, a multivariate analysis (MVA) was performed from initiation of 2L therapy, adjusted for treatment sequence, time interval between initiation of 1L and 2L therapies, Hb ( < 10 vs ≥10 g/dl), ECOG PS (0-1 vs 2-3), and metastatic site (LN/soft tissue only vs non-liver vs liver). Results: 146 pts (IO→Cb n = 43, Cb→IO n = 103) were evaluable with median age 72, 76% men, 78% ECOG PS 0-1, 17.8% with liver metastasis. Baseline factors were balanced except for higher proportion of men in IO→Cb group (91% vs 70%, p = 0.01). Median time interval between initiation of 1L and 2L therapy for IO→Cb and Cb→IO were 15.6mo (4.8-78.1) and 23.0mo (2.1-103.3), respectively. Response rates are summarized (Table). On MVA, treatment sequence was not associated with OS (HR 1.05, p = 0.85). Site of metastasis was the only factor significantly associated with OS (p = 0.002). Conclusions: In our retrospective analysis of cisplatin-ineligible pts with mUC regardless of PD-L1 expression, anti-PD-1/PD-L1 followed by carbo-based chemo or the reverse sequence appeared to confer comparable OS. The observed response rates and time interval between initiation of 1L and 2L therapy are likely contributed by pt selection, where all pts received 2L. Further investigation of the ‘PD-L1 high’ population is warranted, given higher response rates with anti-PD-1/PD-L1 vs ‘PD-L1 low’ population. Ongoing phase III trials will help inform optimal sequencing. Table: see text
Immune checkpoint inhibitors (ICIs) are being increasingly used across cancer types. Emergency room (ER) and inpatient (IP) care, common in patients with cancer, remain poorly defined in this ...specific population, and risk factors for such care are unknown.
We retrospectively reviewed charts for patients with solid tumors who received >1 ICI dose at 1 of 2 sites from January 1, 2011 to April 28, 2017. Demographics, medical history, cancer diagnosis/therapy/toxicity details, and outcomes were recorded. Descriptive data detailing ER/IP care at the 2 associated hospitals during ICI therapy (from first dose to 3 mo after last dose) were collected. The Fisher exact test and multivariate regression analysis was used to study differences between patients with versus without ER/IP care during ICI treatment.
Among 345 patients studied, 50% had at least 1 ER visit during ICI treatment and 43% had at least 1 IP admission. Six percent of ER/IP visits eventually required intensive care. A total of 12% of ER/IP visits were associated with suspected or confirmed immune-related adverse events. Predictors of ER care were African-American race (odds ratio OR: 3.83, P=0.001), Hispanic ethnicity (OR: 3.12, P=0.007), and coronary artery disease (OR: 2.43, P=0.006). Predictors of IP care were African-American race (OR: 2.38, P=0.024), Hispanic ethnicity (OR: 2.29, P=0.045), chronic kidney disease (OR: 3.89, P=0.006), angiotensin converting enzyme inhibitor/angiotensin receptor blocker medication use (OR: 0.44, P=0.009), and liver metastasis (OR: 2.32, P=0.003).
Understanding demographic and clinical risk factors for ER/IP care among patients on ICIs can help highlight disparities, prospectively identify high-risk patients, and inform preventive programs aimed at reducing such care.
Introduction: The objective of this study was to stratify preoperative immune cell counts by cancer specific outcomes in patients with renal cell carcinoma (RCC) and a tumor thrombus after radical ...nephrectomy with tumor thrombectomy. Methods: Patients with a diagnosis of RCC with tumor thrombus that underwent radical nephrectomy with thrombectomy across an international consortium of seven institutions were included. Patients who were metastatic at diagnosis and those who received preoperative medical treatment were also included. Retrospective chart review was performed to collect demographic information, past medical history, preoperative lab work, surgical pathology, and follow up data. Neutrophil counts, lymphocyte counts, monocyte counts, neutrophil to lymphocyte ratios (NLR), lymphocyte to monocyte ratios (LMR), and neutrophil to monocyte ratios (NMR) were compared against cancer-specific outcomes using independent samples t-test, Pearson’s bivariate correlation, and analysis of variance. Results: One hundred forty-four patients were included in the study, including nine patients who were metastatic at the time of surgery. Absolute lymphocyte count preoperatively was greater in patients who died from RCC compared to those who did not (2 vs 1.4; p < 0.001). Patients with tumor pathology showing perirenal fat invasion had a greater neutrophil count compared to those who did not (7.5 vs 5.5; p = 0.010). Patients with metastatic RCC had a lower LMR compared to those without metastases after surgery (2.5 vs 3.2; p = 0.041). Tumor size, both preoperatively and on gross specimen, had an interaction with multiple immune cell metrics ( p < 0.05). Conclusions: Preoperative immune metrics have clinical utility in predicting cancer-specific outcomes for patients with RCC and a tumor thrombus. Additional study is needed to determine the added value of preoperative serum immune cell data to established prognostic risk calculators for this patient population.
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