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650 Background: Management of metastatic renal cell carcinoma (mRCC) is highly individualized and often involves cytoreductive nephrectomy (CN) and systemic therapy (ST). The optimal sequencing of CN and ST is uncertain. A difference in perioperative outcomes based on sequence of CN and ST could influence decision-making. We conducted this NSQIP analysis to assess whether preoperative systemic therapy adversely impacted perioperative outcomes in patients receiving deferred CN. Methods: This analysis was conducted using the American College of Surgeons NSQIP Participant Use Data File for years 2019 and 2020. These years were selected because data on receipt of preoperative therapy is only available since 2019. Inclusion criteria were i) CPT code consistent with nephrectomy, ii) urologist operating surgeon & iii) presence of disseminated cancer. All cases with ICD-10 diagnosis codes not consistent with mRCC were excluded. Groups were stratified by their receipt of preoperative systemic therapy within 90 days before CN and we assessed 46 preoperative and perioperative outcomes. Results: The study cohort included 505 patients with 115 (23%) who received preoperative ST. No differences were noted in perioperative outcomes (Table). Patients receiving preoperative ST were more likely to be on steroids (23% vs. 7%, p0.05). Conclusions: Because preoperative ST did not have an appreciable impact on deferred CN perioperative outcomes, decision making for ST and CN sequencing should not be influenced by perioperative outcomes. Those who undergo deferred CN are unlikely to experience delayed time to surgery or perioperative complications from their ST. [Table: see text]

703 Background: Bone-predominant metastatic renal cell carcinoma (mRCC) is associated with aggressive biology and poor prognosis. The optimal management of these patients (pts) remains not well-established. While contemporary trials showed the superiority of immune checkpoint inhibitors (ICI) compared to vascular endothelial growth factor tyrosine kinase inhibitors (TKI), these pts were often excluded due to non-measurable disease. mRCC bone metastases show an enhanced angiogenesis gene signature suggesting the potential for greater responses to TKI. We test this hypothesis in a retrospective study comparing treatment outcomes for the first line (1L) TKI versus ICI in pts with bone-predominant mRCC. Methods: Pts with mRCC who received care at the Ohio State University Comprehensive Cancer Center from 1/1/2008 to 6/1/2021 were identified through retrospective chart review. Bone-predominant metastasis was defined as the number of bone metastases > extra-osseous metastases. Pts who had ≥1 cycle of treatment and follow-up scans were evaluated for treatment responses per RECIST 1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. The comparisons were made between TKI and ICI cohorts, and the significance was determined by logrank test. Pt who received ICI-TKI in 1L were excluded from the survival analysis due to limited N. Results: A total of 335 pts with mRCC were identified, of which 45 (13.4%) had bone-predominant metastasis. Most of the pts (44/45) had clear cell histology. TKI was the 1L intervention for 21 (47%) while 20 (44%) pts received ICI, and 4 (9%) pts received TKI-ICI. TKI and ICI cohorts were similar for International Metastatic RCC Database Consortium (IMDC) Risk (Table). In the TKI cohort, 19 pts had evaluable responses with ORR of 15.7% and SD of 42%. The mPFS was 5.9 months (95% CI 2.8–9), and mOS was 30.4 months (95% CI 3.3–57.6). In the ICI cohort, 16 had evaluable responses with ORR of 6% and SD of 43.8%. The mPFS was 3.4 months (95% CI 0–8.2), and mOS was 19.3 months (95% CI 14.9–23.7). The hazard ratio was 0.58 for PFS and 0.54 for OS, favoring TKI over ICI, although statistical significance was not reached due to the small sample size (p=0.10 and 0.12, respectively). Conclusions: In this single-center retrospective study, pts with bone-predominant mRCC who received TKI compared to ICI as 1L therapy showed improved ORR, PFS, and OS. These results warrant further investigation in larger studies comparing TKI-containing regimen vs ICI doublet. [Table: see text]

458 Background: Enfortumab vedotin (EV) and, for those with FGFR3 mutations (FGFR3+), erdafitinib, are established therapeutic options for refractory advanced urothelial carcinoma. However, optimal sequencing of these agents remains undefined. Here, we report our experience of EV monotherapy with focus on patients (pts) with FGFR3 alterations. Methods: Pts who were treated with EV were identified. Clinical data and outcomes were extracted. Tumor genomic profiles by the MSK-IMPACT assay as part of standard of care were reviewed for FGFR3 and other commonly altered gene mutations and tumor mutation burden (TMB). Progression-free (PFS) and overall survival (OS) were measured from start of EV therapy and compared with unadjusted log-rank test. Results: 89 patients received EV on completed monotherapy studies (n = 37) or as standard of care. Median age was 62 years (IQR: 62 – 78), 71% were male (n = 63), 28% had liver metastases. Distribution per Bellmunt score (0 – 3) was: 12%, 42%, 37% and 9%. For the entire population, PFS and OS were 5.2 and 11.4 months, respectively, with response rate of 52% among 75 evaluable patients. MSK-IMPACT was available for 80 patients. Overall genomic profile was similar to TCGA cohort except for fewer DNA damage response/repair gene alterations – 15% (ERCC2: 2; ATM: 4, BRCA1: 2, BRCA2: 3, RAD51C: 1) and FGFR3+ rate of 33%. Median TMB was 8.9/Mb (IQR: 5.2 – 13.3). Of the 26 FGFR3+ pts, 8 and 1 received an FGFR3 inhibitor (FGFR3i) before and after EV, respectively. 17 pts have not been exposed to FGFR3i; 13 of whom have progressed on EV and 9 died. Compared to FGFR3- pts, FGFR3+ pts with no prior FGFRi had significantly shorter median PFS on EV (2.5 vs. 6.8 months; HR 0.33 [0.14 – 0.80] p < .01) and trend towards shorter median OS (4.9 vs. 14.6 months; HR 0.42 [0.16 – 1.08] p > .05). PFS on EV among FGFR3+ pts with prior FGFR3i exposure was 6.7 months, similar to FGFR3- pts (HR 0.77 [0.30 – 1.96] p = .6). Response rates for FGFR3+ with and without prior FGFRi, and FGFR3- pts on EV were 4/7 (50%), 5/13 (38%) and 29/48 (60%). Conclusions: In this retrospective study, FGFR+ patients who receive EV first appear to have shorter PFS and lower ORR than those who have received prior FGFRi. Prospective studies on the sequence of EV and FGFR3i in FGFR3+ pts are warranted.

TPS10541 Background: Medical educators have adopted simulation-based exercises (SBEs) because studies of their use in the aviation industry and other technical fields have shown that they reduce human error. While use of simulation has increased in undergraduate and graduate medical education, it hasn’t been used as frequently in educating subspecialty fellows. Fewer than 5% of participants in a survey of different subspecialists indicated that simulations were part of their fellowship curriculum (1) even though simulation-based training is an ACGME program requirement (2). Chemotherapy infusion reactions (CIRs) occur with about 5% of all cytotoxic chemotherapies and even more frequently with biologics (3). These CIRs present significant morbidity and cost. HFS improves knowledge and confidence in medical trainees (4). Therefore, I designed a high fidelity simulation (HFS)-based curriculum to measure fellows’ current medical knowledge and provide a mechanism for gaining increased understanding and confidence. Across subspecialty graduation medical education, only one SBE with IRs has been performed, and that project aimed only to measure existing knowledge (5). This project aims to measure oncology fellows’ knowledge of and confidence in CIR management, measure attitudes regarding SBEs, measure improvement in knowledge following the SBEs, and assess for changes in behavior (management of CIRS) that may occur following these interventions. Methods: The HFS takes place in the VA Hospital Interdisciplinary Simulation and Education Center, which consists of a programmable mannequin that can “talk” through a speaker and convey physical exam signs in an “outpatient clinic.” Participants will interact with the mannequin, who will be a patient experiencing a paclitaxel infusion reaction. An evaluator will be grading the participant’s actions with an OSCE style checklist. Immediate debriefing will be followed by a didactic. Participants will complete post-intervention surveys regarding their confidence in and knowledge of management of CIRS. Participants will later be evaluated on their attitudes regarding the simulation, their knowledge of CIR management, and will also provide critique of the same interaction done by another provider. These HFS-based activities will allow evaluation of fellows’ current knowledge of and comfort with CIRS, fellows’ attitudes regarding the intervention, improvement in knowledge occurred following the intervention, and anticipated change in management.