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34 Background: The American Society of Clinical Oncology (ASCO) and the Friends of Cancer Research (FCR) published a joint statement addressing clinical eligibility for characteristics lacking adequate representation in recent studies (Kim et al., Clin Cancer Res 2021). Herein, we aimed to identify the frequency of other potentially excessive exclusion criteria in the context of metastatic prostate cancer. Methods: The eligibility criteria of advanced prostate cancer studies with start dates between June 30, 2012 and June 30, 2022 were identified through Clinicaltrials.gov. MeSH (Medical Subject Headings) terms in our query were “(metastatic OR advanced OR stage IV OR unresectable) AND (prostate cancer OR prostate adenocarcinoma)”. Our study included trials conducted worldwide and examined patients aged 18 and over in phase I-III trials. To narrow the scope of study, trials including more than one cancer type (basket trials) as well as those focusing on radiation therapy were not included in the study. Descriptive statistics were used to determine the frequency of eligibility criteria while the Fisher’s exact test or chi-square test were performed to demonstrate association between type of treatment and exclusion criteria. Results: 265 of 699 (37.9%) clinical trials within the specified search had sufficiently available data for evaluation. Of these, 136 (51.3%), 51 (19.2%), 26 (9.8%), 20 (7.5%), 19 (7.2%), and 7 (2.6%) of trials investigated treatment with combination therapy, hormone therapy, targeted therapy, immunotherapy, radioligand therapy, and chemotherapy, respectively. The most common ASCO-FCR-cited exclusion criteria in the studies were brain metastases (161/265, 60.8 %), HIV positivity (123/265, 46.4%), HBV/HCV positivity (122/265, 46.0%), and concurrent malignancies (41/265, 16.6%). Statistically significant relationships were identified between type of treatment along with status of brain metastases, HIV, and HBV/HCV (p=0.011

678 Background: Recent studies have suggested an association between the time-of-day of ICI infusions and disease outcomes, including progression free survival and overall survival, among patients with cancer. (Qian et al Lancet Oncology 2021). We sought to identify whether such an association exists in patients with mRCC receiving ICIs. Methods: Patients with mRCC treated with nivolumab alone, or in combination with ipilimumab, in either first- or second-line treatment were retrospectively identified. Patients who received

614 Background: Racial minorities experience intersecting forms of marginalization and suffer significant healthcare disparities. Prospective trials have shown similar outcomes with partial and radical nephrectomy among patients with localized RCC (Van Poppel et al Eur Urol 2011), and multiple studies suggest increasing use of the former technique (Breau et al Can J Urol 2020). We hypothesize that patients from minority groups, as well as those with non-private insurance, will have less access to this specialized procedure and therefore have a higher rate of radical nephrectomy. Methods: We utilized the California Office of Statewide Health Planning and Development (OSHPD) database that collects information from all inpatient admissions, emergency room visits and inpatient/outpatient procedures in the state. All patients undergoing nephrectomy (both partial and radical) were identified from Jan 1, 2012 to Dec 31, 2018 using CPT and ICD-9/10 codes to identify patients. Demographic data was collected with specific attention to race and payor status. Univariate and multivariate analyses were conducted to determine the association between demographic data and procedure type. Results: In total, 31,093 patients were identified; 57% were males, with a mean age of 58 years. Among these, 16,142 (51.9%), 8,645 (27.8%), 2,795 (9.0%), 2,032 (6.5%) and 1,479 (4.8%) were characterized as White, Hispanic, Asian, Black and other, respectively. Partial nephrectomy and radical nephrectomy were performed in 15,840 (50.9%) and 15,253 (49.1%) of patients. By race, partial nephrectomy was performed in 8,576 (53.1%), 4,107 (47.5%), 1,286 (46.0%), 1,124 (55.3%) and 747 (50.5%) of White, Hispanic, Asian, Black and other patients, respectively (p

612 Background: A consensus statement from the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (FCR) collaboration highlights the importance of expanding eligibility criteria in cancer trials to more accurately reflect the real-world population (Kim et al., Clin Cancer Res 2021). We sought to characterize use of overly restrictive eligibility criteria in renal cell carcinoma (RCC) trials in the context of ASCO-FCR recommendations. Methods: Studies containing the MeSH terms “(metastatic OR advanced OR stage IV or unresectable) AND (kidney cancer OR renal cell carcinoma OR renal cell cancer)” from June 30, 2012 to June 30, 2022 were identified on the ClinicalTrials.gov platform. Our search query’s inclusion criteria identified international studies examining adult patients aged ≥ 18 in phase I-III trials. Exclusion criteria comprised pan-cancer studies, trials involving localized treatments, radiation therapy, and prognostic tools. Descriptive statistics were used to characterize the frequency of restrictive eligibility criteria across studies, while Fisher’s exact test or chi-square test were utilized to determine the association between treatment type and exclusion criteria. Results: The content of 423 RCC trials were analyzed, of which 112 (26.5%) had adequate data available. 48 (42.9%), 44 (39.3%) and 18 (16.1%) studies examined combination therapy, targeted therapy, and immunotherapy, respectively. The presence of HIV positivity, HBV/HCV positivity, brain metastases, and concurrent malignancies accounted for the most frequently cited exclusionary criteria, seen in 83/112 (74.1%), 60/112 (53.6%), 37/112 (33.0%), and 9/112 (8.0%) studies respectively. Differences in the use of HIV positivity (p

662 Background: Mounting data suggests that dietary modification and supplement use, including probiotics, may modulate outcomes with immunotherapy in cancer therapy (Spencer CN et al. Science 2021; Dizman N et al. Nature Medicine 2022). For the first time, we sought to quantify the use of these measures among patients with metastatic renal cell carcinoma (mRCC). Methods: An online survey was administered by Kidney Cancer Research Alliance (KCCure), a non-profit patient advocacy group, between July 22 and Sept 22 to a patient mailing list (N=1,532). Only patients diagnosed with mRCC and under active systemic therapy were included for analysis in the current study. Select questions were directed at dietary modification patterns and supplement usage. Patients were additionally surveyed regarding out-of-pocket spending patterns related to supplement purchases and to what extent they shared information about their supplement intake with their physicians. The student's t-test and Chi-square test were used to compare sociodemographic characteristics between participants who did and did not report supplement intake. Results: Out of 1,062 patients with renal cell carcinoma who participated in this survey, 289 met the inclusion criteria (M:F, 145:143). The median age was 61. The majority of patients identified themselves as white (91%), were from the US (86.8%), and had completed a bachelor's degree (52.9%). 21.1%, 46.1%, and 32.6% lived in urban, suburban, and rural locations, respectively. The most common reported first-line treatments were nivolumab/ipilimumab (32.4%) and axitinib/pembrolizumab (13.1%). 22.4% of respondents reported spending >$100/month on supplements, and 8.3% reported spending >$250/mo. Dietary modifications following a cancer diagnosis were reported by 34.9% of respondents, out of which 19.8% followed the Mediterranean diet and 18.8% adopted a ketogenic diet. 50.8% of respondents reported supplement intake. The most widely utilized supplements were cannabidiol (CBD) oil/marijuana, probiotics, and Vitamin C, reported by 28.0%, 24.2%, and 18.6% of respondents, respectively. 83.4% of respondents noted that they consistently report supplement usage to their physicians. There were no statistically significant associations between supplement use and age, sex, living area, or education. Conclusions: A substantial proportion of patients with mRCC use dietary modification and supplements as an adjunct to their antineoplastic treatment. Interventions such as probiotic use and ketogenic diets, which are the subject of a prospective study in mRCC (NCT05119010; NCT05122546), may already be used by many patients. More careful attention to nutrition and supplement use in clinical trial candidates may minimize the impact of these potential confounders.

453 Background: American Society of Clinical Oncology (ASCO) and the Friends of Cancer Research (FCR) underscored the need to broaden eligibility criteria in cancer trials to increase patient accrual, expand access to investigational treatments, and enhance generalizability of study results (Kim et al., Clin Cancer Res 2021). While eligibility criteria intend to prioritize patient safety and define a specific study population, these criteria are often based on outdated standards and may not be reflective of real-world practice. Our study aimed to characterize the proportion of aUC trial eligibility criteria according to the ASCO-FCR statement. Methods: Protocols indexed on ClinicalTrials.gov with start dates from June 30, 2012 to June 30, 2022 were evaluated. MeSH terms used in our query were “(metastatic OR advanced OR stage IV OR unresectable) AND (bladder cancer OR upper tract urothelial carcinoma OR upper tract urothelial cancer)”. International studies enrolling patients aged 18 and over in phases I-III were included. Studies examining multiple cancer types as well as those involving localized treatments (e.g., surgery or ablation), radiation therapy, and prognostic tools were excluded. Analyses of eligibility criteria focused on those highlighted in the ASCO-FCR statement; descriptive statistics were used to define the frequency of eligibility criteria and chi-square and Fisher’s exact test were used to determine their association with treatment type. Results: Overall, 205 urothelial cancer trials were assessed, with 37 (18.0%) having publicly accessible data. Of these, 13 (35.1%) evaluated combination therapy, 11 (29.7%) evaluated immunotherapy, 8 (21.6%) evaluated targeted therapy, and 5 (13.5%) evaluated chemotherapy. HIV positivity, HBV/HCV positivity, brain metastases, and concurrent malignancies were found to be exclusion criteria in 89.2% (33/37), 56.8% (21/37), 35.1% (13/37), and 5.4% (2/37) of studies, respectively. While brain metastases, concurrent malignancies, and HBV/HCV positivity were found to be independent of the class of therapy, a statistically significant association was observed with HIV positivity. Specifically, trials evaluating combination therapy (100.0%), immunotherapy (100.0%) and targeted therapy (87.5%) more frequently included HIV positivity as an exclusion criterion as compared to chemotherapy trials (40.0%). Conclusions: A modest percentage of a UC studies from the last decade were observed to report overly restrictive eligibility criteria as defined by the ASCO-FCR statement. HIV positivity and HBV/HCV positivity were commonly identified exclusion criteria, despite limited evidence that these criteria significantly impact drug efficacy and tolerability. Reassessing and updating eligibility criteria will ensure that the resulting data is more reflective and inclusive of a real-world population.

613 Background: Existing literature has reported differences in clinical outcomes by ethnicity in patients receiving immune checkpoint inhibitors (Olsen et al Front Oncol 2021). We investigated real-world outcomes between Latinx and non-Latinx mRCC patients treated with first-line nivo/ipi within a safety-net healthcare system and at a tertiary care center in Southern California. Methods: We performed a retrospective analysis of mRCC patients who received nivo/ipi within the Los Angeles County Department of Health Services (DHS), a safety-net healthcare system, and the City of Hope Comprehensive Cancer Center (COH), a tertiary oncology center, between Jan. 1, 2015 and Dec. 31, 2021. Patients were identified using institutional databases and clinical data were compiled from electronic health records. Patients with pathologic diagnosis of mRCC, age > 18 years and receipt of nivo/ipi as first-line therapy were included. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards model with adjustments for other covariates. Results: Of 94 patients, 66 (70%) were male, 90 (94%) had clear-cell histology, and 87 (93%) had IMDC intermediate/poor risk disease. Forty patients (43%) were Latinx. Fifty (53%) and 44 (47%) patients received their care at a tertiary care center and within a safety-net healthcare system, respectively. Most Latinx patients (95%) were treated at DHS, and most non-Latinx patients (89%) were treated at COH. Latinx patients were significantly older than non-Latinx patients (59.5 vs 55 years, p=0.008). IMDC risk classification, body mass index, history of nephrectomy, and number of comorbidities were similar between both groups. Pooled analysis by ethnicity demonstrated significantly shorter PFS in Latinx versus non-Latinx patients (10.1 vs 25.2 months, HR 3.61, 95% CI 1.96-6.66, p=

600 Background: The outcomes of patients with brain metastases from renal cell carcinoma (RCC) are not well characterized due to exclusion of these patients from clinical trials. Methods: Using the IMDC, patients with brain metastases from RCC at the initiation of first-line therapy were analyzed. Baseline patient characteristics, brain-directed local therapies, clinician assessment of best overall response as per RECIST 1.1, and overall survival (OS) were compared across first-line therapies, namely immuno-oncology (IO)-based combination therapy (IO/IO or IO/vascular endothelial growth factor (VEGF)) and anti-VEGF monotherapy (sunitinib or pazopanib). Results: The overall cohort of patients with brain metastases included 775 patients, consisting of 78/1298 (6.0%) and 697/8633 (8.1%) in the IO-based and anti-VEGF cohorts, respectively (p = 0.009). Among the baseline patient characteristics, only the proportion of patients receiving whole-brain radiotherapy differed significantly across the IO-based and anti-VEGF cohorts with proportions of 25.0% and 55.7%, respectively (p < 0.001). Best overall response in all disease sites was 3.4% complete response (CR), 25.9% partial response (PR), 39.7% stable disease (SD), and 31% progressive disease (PD) in the IO-based cohort, whereas it was 0.7% CR, 29.6% PR, 36.7% SD, and 33.0% PD in the anti-VEGF cohort (p = 0.223). The following factors were significantly associated with longer OS on multivariable analysis: IMDC favourable-/intermediate-risk (HR 0.49, 95% CI 0.37–0.65; p < 0.001), IO-based combination therapy (HR 0.51, 95% CI 0.29–0.92; p = 0.026), neurosurgery (HR 0.62, 95% CI 0.47–0.83; p = 0.001), and stereotactic radiosurgery (HR 0.64, 95% CI 0.49–0.84; p = 0.001). Conclusions: Patients with brain metastases receiving IO-based combination therapy may have longer OS than those receiving anti-VEGF monotherapy. Brain-directed local therapies including neurosurgery and stereotactic radiosurgery were associated with longer OS. [Table: see text]

220 Background: Activating genomic alterations (GA) in BRAF are rare in aPC and their impact on pathogenesis is poorly understood. However, emerging data suggest that these GA may represent clinically actionable targets (Fenor et al, Clin Transl Oncol, 2022). Using comprehensive genomic profiling (CGP) performed in a single commercial lab, we characterized the GA landscape of BRAF-activated tumors in aPC patients (pts). Methods: Tissue(N=15,864) and liquid (N=7,566) biopsies from aPC pts were profiled using FoundationOne CDx and FoundationOne Liquid CDx CGP assays, respectively. Each assay covers 324 cancer-related genes, including the full coding region of BRAF and introns 7-10, with additional sensitivity in exons 11-18 in the liquid assay. Activating GA were defined as hotspot missense mutations, in-frame indels in the kinase domain, or rearrangements (RE) that preserve the kinase domain. Tissue biopsies from non-aPC cancer types (N= 275,151) were used for comparison. Results: BRAF-activating GA were detected in 520/15,864 (3.3%) tissue biopsies: RE were the most common GA (243 samples, 1.5%), followed by K601E (101, 0.6%), and G469A (58, 0.4%). Median age of pts with BRAF-altered tumors was 69 (interquartile range 63-76), compared to 68 for BRAF wild-type (interquartile range 62-74). Rearrangement breakpoints occurred most frequently in intron 8 (37%), intron 9 (28%), intron 10 (20%), and intron 7 (13%). The most common RE were BRAF N-terminal truncations removing the auto-inhibitory domain (22%), SND1-BRAF fusions (13%), intragenic BRAF deletions of the auto-inhibitory domain (12%), and TMPRS22-BRAF fusions (5%). When studying cases with BRAF-activating GA compared to wild-type, we noted a larger proportion of CDK12 mutations (9.2% vs 5.2%, p=0.018), and a depletion of TMPRSS2-ERG fusions (11% vs 32%, p

455 Background: Prior studies have described significant disparities in the selection of urinary diversion (UD) in patients with localized bladder cancer undergoing cystectomy. Although the choice of UD has not been shown to impact oncologic outcomes, continent urinary diversions (CUD) are associated with lower rates of in-hospital complications and mortality, but higher costs (Farber NJ et al. Bladder Cancer 2018). Male gender, White race, and higher income have been associated with proportionally higher rates of CUD than patients from other races or those without private insurance (Barocas DA et al. Cancer 2014 and Rios EM et al. Urology 2020). Utilizing the California Office of Statewide Health Planning and Development (OSHPD) database, we investigated potential barriers to CUD in patients with bladder cancer undergoing radical cystectomy. Methods: The current procedural terminology (CPT) and the international classification of diseases (ICD)-9/10 codes were used to identify patients with bladder cancer undergoing radical cystectomy from Jan 1, 2012, through Dec 31, 2018. Type of UD and demographic data such as race and payer status were collected. Univariate and multivariable analyses were conducted to determine the association between demographic variables and CUD use. Results: In total, 9,342 patients who underwent radical cystectomy were identified, of which 3,061 had UD status noted. Of these, 13.2% (404/3061) were continent and 86.2% (2,657/3061) were incontinent diversions. CUD use was significantly higher in White patients (14.1%; 320/2276) compared to Asian (12.8%; 24/187), Hispanic (9.5%; 30/316) or Black (5%; 6/119) patients (P=0.01). Use of CUD was significantly higher in patients with private insurance (23.2%; 167/721) compared to those with Medicare (10.2%; 207/2023) or indigent (MediCal/Medicaid; 8.6%; 23/269; p

654 Background: IO-based regimens have demonstrated substantial efficacy in the management of metastatic clear-cell RCC (mccRCC), where they currently represent the standard of care. ChRCC has a dismal prognosis in the metastatic setting. Recent clinical trials evaluating IO-based regimens across non-ccRCC subtypes identified a preliminary poor response in advanced ChRCC, but were limited by low sample sizes. We sought to comprehensively evaluate the outcomes of patients with ChRCC treated with IO-based regimens. Methods: Using real-world data from the International Metastatic RCC Database Consortium (IMDC), we conducted a retrospective analysis of patients with advanced ChRCC who received IO-based therapies, including dual IO therapy or IO + VEGF targeted therapy (VEGF-TT), in the first-line setting. The primary outcome was overall survival (OS). Secondary outcomes included time to treatment failure (TTF) and ORR. Cox proportional hazards models were used to adjust for age and IMDC risk groups as covariates. A logistic regression was used to determine the association between the odds of achieving a response and RCC subtype. Results: We identified 31 patients with advanced ChRCC and 856 patients with ccRCC treated with IO-based therapies in the first-line setting, with a median age of 61.5 years (IQR: 51.5-69.0). Compared to patients with ccRCC who received IO-based therapies as initial regimens, patients with ChRCC had a lower OS (median OS: 24.7 vs. 50.5 months, respectively; p