Search

Enfortumab Vedotin (EV) is approved for metastatic urothelial carcinoma (mUC) progressing post-platinum and PD1/L1 inhibitor therapy. Erdafitinib is approved for post-platinum mUC with activating somatic genomic alterations (GAs) in FGFR2/3. Information on the activity of EV in mUC with FGFR2/3 alterations will facilitate optimal clinical management. In this multi-center, retrospective analysis, we assessed the overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) to EV in mUC patients with and without FGFR2/3 GAs including mutations and fusions. Multivariable cox-regression and logistic regression analyses with 2-tailed p-values were used to evaluate the association of GAs with outcomes. A majority of the evaluable 60 patients were male (44/60, 78%), exhibited ECOG performance score 0–1 (53/60, 88.3%) and had a median age of 70.5 (range 48 – 88) years when starting EV. GAs in FGFR2/3 did not influence the ORR (p=0.32), OS (p=0.79) or PFS (p = 0.32) with EV. In conclusion, FGFR2/3 GAs did not appear to compromise major outcomes with EV in mUC. Larger studies are required to further evaluate the impact of FGFR2/3 GAs on the activity of EV and the optimal sequencing of EV and erdafitinib in mUC.

Supplemental Digital Content is available in the text., Patients with advanced melanoma treated with immune checkpoint inhibitors can experience ongoing disease control after treatment discontinuation without subsequent systemic anticancer therapy. We previously defined a novel outcome, treatment-free survival (TFS), as the time between protocol therapy cessation and subsequent therapy initiation/death. We assessed the effect of established prognostic variables [lactate dehydrogenase (LDH), programmed death ligand 1 status, BRAF mutation status, performance status, and sex] on TFS in different treatment scenarios: treatment until toxicity/progression with frequent early cessation (nivolumab plus ipilimumab), treatment until toxicity/progression with a well-tolerated regimen (nivolumab), and treatment for a short fixed duration (ipilimumab). Data were pooled from 1077 patients with advanced melanoma treated in the CheckMate 069 and 067 trials. TFS was defined as the area between the Kaplan–Meier curves for time to therapy cessation and time to subsequent therapy initiation/death. TFS was estimated by restricted mean (r-mean) survival time at 36 months since randomization. Clinically meaningful TFS (r-mean TFS 3.7–12.7 months) was observed across all patient subgroups. TFS was longest in patients treated with nivolumab plus ipilimumab. The largest differences in r-mean TFS were observed with LDH in the nivolumab plus ipilimumab and ipilimumab treatment groups (TFS difference 4.7 and 4.9 months, respectively). In the nivolumab group, there was little difference in TFS across subgroups (r-mean TFS 3.7–5.5 months). TFS was sensitive to prognostic subgroup differences; however, duration of treatment affected the sensitivity of TFS. These results provide further support for TFS as a clinical outcome measure.

PURPOSE Immune checkpoint inhibitors (ICIs) are standard therapy in metastatic renal cell carcinoma (RCC). The safety and activity of the combination of ipilimumab and nivolumab in patients who have received prior ICI targeting the programmed death 1 (PD-1) pathway remains unknown. We evaluated ipilimumab and nivolumab in patients with metastatic RCC after prior treatment with anti–PD-1 pathway–targeted therapy. PATIENTS AND METHODS Patients with metastatic RCC who received prior anti–PD-1 pathway-targeted therapy and subsequently received ipilimumab and nivolumab were reviewed. Objective response rate and progression-free survival per investigator assessment were recorded. Toxicity of ipilimumab and nivolumab was also assessed. RESULTS Forty-five patients with metastatic RCC were included. All patients (100%) received prior ICIs targeting the PD-1 pathway. The median age was 62 years (range, 21-82 years). At a median follow-up of 12 months, the objective response rate to ipilimumab and nivolumab was 20%. The median progression-free survival while on ipilimumab and nivolumab was 4 months (range, 0.8-19 months). Immune-related adverse events (irAEs) of any grade with ipilimumab and nivolumab were recorded in 29 (64%) of the 45 patients; grade 3 irAEs were recorded in 6 (13%) of the 45 patients. CONCLUSION Ipilimumab and nivolumab demonstrated antitumor activity with acceptable toxicity in patients with metastatic RCC who had prior treatment with checkpoint inhibition.

Purpose: Patients discontinuing immuno-oncology regimens may experience periods of disease control without need for ongoing anticancer therapy, but toxicity may persist. We describe treatment-free survival (TFS), with and without toxicity. Patients and Methods: Data were analyzed from the randomized phase III CheckMate 214 trial of nivolumab plus ipilimumab (n = 550) versus sunitinib (n = 546) for treatment-naïve, advanced renal cell carcinoma (aRCC). TFS was estimated by the 42-month restricted mean times defined by the area between Kaplan–Meier curves for two time-to-event endpoints defined from randomization: time to protocol therapy cessation and time to subsequent systemic therapy initiation or death. TFS was subdivided as TFS with and without toxicity by counting days with ≥1 grade ≥3 treatment-related adverse event (TRAE). Results: At 42 months since randomization, 52% of nivolumab plus ipilimumab and 39% of sunitinib intermediate/poor-risk patients were alive; 18% and 5% surviving treatment-free, respectively. Among favorable-risk patients, 70% and 73% of nivolumab plus ipilimumab and sunitinib patients were alive; 20% and 9% treatment-free. Over the 42-month period, mean TFS was over twice as long after nivolumab plus ipilimumab than sunitinib for intermediate/poor-risk (6.9 vs. 3.1 months) and three times as long for favorable-risk patients (11.0 vs. 3.7 months). Mean TFS with grade ≥3 TRAEs was a small proportion of time for both treatments (0.6 vs. 0.3 months after nivolumab plus ipilimumab vs. sunitinib for intermediate/poor-risk, and 0.9 vs. 0.3 months for favorable-risk patients). Conclusions: Patients initiating first-line nivolumab plus ipilimumab for aRCC spent more survival time treatment-free without toxicity versus those on sunitinib, regardless of risk group.

Essentials Intracranial hemorrhage (ICH) is common in patients with brain tumors. We compared rates of ICH with DOACs and low molecular weight heparin. DOACs were associated with a lower incidence of ICH in primary brain tumors. DOACs appear safe to administer to patients with brain tumors. SUMMARY: Background Direct oral anticoagulants (DOACs) are efficacious in the treatment of cancer-associated thrombosis but are associated with an increased risk of hemorrhage compared with low-molecular-weight heparin in certain malignancies. Whether the DOACs increase the incidence of intracranial hemorrhage (ICH) in patients with brain tumors is not established. Objectives To determine the cumulative incidence of ICH in DOACs compared with Low-molecular-weight heparin (LMWH) in patients with brain tumors and venous thromboembolism. Patients and methods A retrospective comparative cohort study was performed. Radiographic images for all ICH events were reviewed and the primary endpoint was cumulative incidence of ICH at 12 months following initiation of anticoagulation. Results and conclusions A total of 172 patients with brain tumors were evaluated (42 DOAC and 131 LMWH). In the primary brain tumor cohort (n = 67), the cumulative incidence of any ICH was 0% in patients receiving DOACs vs. 36.8% (95% confidence interval [CI], 22.3-51.3%) in those treated with LMWH, with a major ICH incidence of 18.2% (95% CI, 8.4-31.0). In the brain metastases cohort (n = 105), DOACs did not increase the risk of any ICH relative to enoxaparin, with an incidence of 27.8% (95% CI, 5.5-56.7%) compared with 52.9% (95% CI, 37.4-66.2%). Similarly, DOAC did not increase the incidence of major ICH in brain metastases, with a cumulative incidence 11.1% (95% CI, 0.5-40.6%) vs. 17.8% (95% CI, 10.2-27.2%). We conclude that DOACs are not associated with an increased incidence of ICH relative to LMWH in patients with brain metastases or primary brain tumors.

BackgroundCD73–adenosine signaling in the tumor microenvironment is immunosuppressive and may be associated with aggressive renal cell carcinoma (RCC). We investigated the prognostic significance of CD73 protein expression in RCC leveraging nephrectomy samples. We also performed a complementary analysis using The Cancer Genome Atlas (TCGA) dataset to evaluate the correlation of CD73 (ecto-5′-nucleotidase (NT5E), CD39 (ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)) and A2 adenosine receptor (A2AR;ADORA2A) transcript levels with markers of angiogenesis and antitumor immune response.MethodsPatients with RCC with available archived nephrectomy samples were eligible for inclusion. Tumor CD73 protein expression was assessed by immunohistochemistry and quantified using a combined score (CS: % positive cells×intensity). Samples were categorized as CD73negative(CS=0), CD73lowor CD73high(< and ≥median CS, respectively). Multivariable Cox regression analysis compared disease-free survival (DFS) and overall survival (OS) between CD73 expression groups. In the TCGA dataset, samples were categorized as low, intermediate and highNT5E,ENTPD1andADORA2Agene expression groups. Gene expression signatures for infiltrating immune cells, angiogenesis, myeloid inflammation, and effector T-cell response were compared betweenNT5E,ENTPD1andADORA2Aexpression groups.ResultsAmong the 138 patients eligible for inclusion, ‘any’ CD73 expression was observed in 30% of primary tumor samples. High CD73 expression was more frequent in patients with M1 RCC (29% vs 12% M0), grade 4 tumors (27% vs 13% grade 3 vs 15% grades 1 and 2), advanced T-stage (≥T3: 22% vs T2: 19% vs T1: 12%) and tumors with sarcomatoid histology (50% vs 12%). In the M0 cohort (n=107), patients with CD73hightumor expression had significantly worse 5-year DFS (42%) and 10-year OS (22%) compared with those in the CD73negativegroup (DFS: 75%, adjusted HR: 2.7, 95% CI 1.3 to 5.9, p=0.01; OS: 64%, adjusted HR: 2.6, 95% CI 1.2 to 5.8, p=0.02) independent of tumor stage and grade. In the TCGA analysis, highNT5Eexpression was associated with significantly worse 5-year OS (p=0.008).NT5EandENTPD1expression correlated with higher regulatory T cell (Treg) signature, whileADORA2Aexpression was associated with increased Treg and angiogenesis signatures.ConclusionsHigh CD73 expression portends significantly worse survival outcomes independent of stage and grade. Our findings provide compelling support for targeting the immunosuppressive and proangiogenic CD73–adenosine pathway in RCC.

Background Intracranial hemorrhage (ICH) is a common and often devastating outcome in patients with brain tumors. Despite this, there is little evidence to guide anticoagulation management following an initial ICH event. Objectives To analyze the risk of recurrent hemorrhagic and thrombotic outcomes after an initial ICH event in patients with brain tumors and prior venous thromboembolism (VTE). Patients and Methods A retrospective cohort study was performed. Radiographic images obtained after initial ICH were reviewed for the primary outcomes of recurrent ICH and VTE. Results and Conclusions A total of 79 patients with brain tumors who developed ICH on anticoagulation for VTE were analyzed. Fifty‐four patients (68.4%) restarted anticoagulation following ICH. The cumulative incidence of recurrent ICH at 1 year was 6.1% (95% confidence interval [CI], 1.5‐15.3) following reinitiation of anticoagulation. Following a major ICH (defined as an ICH >10 mL in size, causing symptoms, or requiring intervention), the rate of recurrent ICH upon reexposure to anticoagulation was 14.5% (95% CI, 2.1‐38.35), whereas the rate of recurrent ICH following smaller ICH was 2.6% (95% CI, 0.2%‐12.0%). Mortality following a recurrent ICH on anticoagulation was 67% at 30 days. The cumulative incidence of recurrent VTE was significantly lower in the restart cohort compared to patients who did not restart anticoagulation (8.1% vs 35.3%; P = .003). We conclude that resumption of anticoagulation is lowest among patients with metastatic brain tumors with small initial ICH. Following an initial major ICH, resumption of anticoagulation was associated with a high rate of recurrent ICH.

To compare healthcare resource utilization (HRU) and costs associated with dose-dense methotrexate, vinblastine, doxorubicin, cisplatin (ddMVAC) and gemcitabine, cisplatin (GC) as neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC).Patient treated at Dana-Farber Cancer Institute from 2010 to 2019 were identified. HRU data on chemotherapy administered, supportive medications, patient monitoring, clinic, infusion, emergency department (ED) visits and hospitalization were collected retrospectively. Unit costs for HRU components were obtained from the Centers for Medicare and Medicaid Website and HRU was compared between groups using quantile regression analysis.137 patients were included; 51 received ddMVAC and 86 GC. Baseline characteristics were similar, except lower mean age (P0.001) and higher proportion of ECOG-PS = 0 (P0.001) for ddMVAC. ddMVAC required more granulocyte-colony stimulating factor support (P0.001), central line placement (P = 0.017), cardiac imaging (P0.001), and infusion visits (P0.001), whereas GC required more clinic visits. ED visits were higher for ddMVAC (P = 0.048), while chemotherapy cycle delays and hospitalization days were higher for GC (P = 0.008). After adjusting for ECOG-PS and age, the cost per patient was approximately 41% lower (95%CI: 28% to 52%; P0.001) for GC vs. ddMVAC, which translated to a median adjusted cost savings of $7,410 (95%CI: $5,474-$9,347) per patient.Although excess HRU did not clearly favor one regimen, adjusting for PS and age indicated lower costs with GC vs. ddMVAC. Given the similar cumulative cisplatin delivery with both regimens, the associated values and costs supports the preferential selection of GC in the neoadjuvant setting of MIBC.

BackgroundTreatment-free survival (TFS) characterizes disease control after discontinuation of immune checkpoint inhibitors (ICIs) until subsequent therapy or death. We previously evaluated TFS in a pooled analysis of the CheckMate 067 and CheckMate 069 trials of the ICIs nivolumab and ipilimumab, alone or in combination, in patients with advanced melanoma after minimum follow-up of 36 months. This analysis investigated TFS differences between treatments in CheckMate 067 after a minimum follow-up of 60 months, and their relation to overall survival (OS) differences.MethodsData were from 937 patients who initiated treatment (nivolumab plus ipilimumab, nivolumab, or ipilimumab) in CheckMate 067 (NCT01844505). TFS was defined as the area between the Kaplan-Meier curves for time to protocol therapy cessation and time to subsequent systemic therapy initiation or death, each measured from randomization. TFS was partitioned as time with and without toxicity. Toxicity included persistent and late-onset grade ≥2 select treatment-related adverse events (ie, those of potential immunologic etiology). The area between Kaplan-Meier curves was estimated by the difference in 60-month restricted-mean times of the endpoints. Between-group differences were estimated with bootstrapped 95% CIs.ResultsAt 60 months from randomization, 39%, 24%, and 11% of patients assigned to treatment with nivolumab plus ipilimumab, nivolumab, and ipilimumab, respectively, had survived and were treatment-free. The 60-month mean TFS was approximately twice as long with the combination (19.7 months) than with nivolumab (9.9 months; absolute difference, 9.8 (95% CI 6.7 to 12.8)) or ipilimumab (11.9 months; absolute difference, 7.8 (95% CI 4.6 to 11.0)). In the respective groups, mean TFS represented 33% (8% with and 25% without toxicity), 17% (2% and 14%), and 20% (3% and 17%) of the 60-month period. Compared with 36-month estimates, mean TFS over the 60-month period represented slightly greater percentages of time in the nivolumab-containing regimen groups and a lesser percentage in the ipilimumab group. TFS differences between the combination and either monotherapy increased with longer follow-up.ConclusionsAlong with improved long-term OS with the nivolumab-containing regimens versus ipilimumab, TFS without toxicity was sustained with nivolumab plus ipilimumab versus either monotherapy, demonstrating larger between-group differences with extended follow-up.

Venous thromboembolism is commonly diagnosed in patients with primary and secondary brain tumors. Anticoagulation management in the setting of brain tumors is complicated by the high background rate of spontaneous intracranial hemorrhage. Until recently, there was limited evidence to support the decision to administer therapeutic anticoagulation in the setting of brain metastases or primary brain tumors. The current evidence suggests that the safety profile of therapeutic low molecular weight heparin for the treatment of venous thromboembolism is contingent on whether the origin of brain tumor is primary (i.e., glioma) versus secondary. In patients with brain metastases, the rate of intracranial hemorrhage often exceeds 20% but is not influenced by the administration of low molecular weight heparin. In contrast, in primary brain tumors such as glioma, therapeutic anticoagulation is associated with an increased risk of intracranial hemorrhage that can negatively impact survival. This chapter reviews the underlying mechanisms contributing to thrombosis and hemorrhage in brain tumors and summarizes the current evidence and approaches in anticoagulation to treat venous thromboembolism.

472 Background: Enfortumab Vedotin (EV), an antibody-drug conjugate that targets nectin-4, is approved for metastatic urothelial carcinoma (mUC) progressing post-platinum and PD1/L1 inhibitor therapy. Erdafitinib is approved in patients for post-platinum mUC with activating genomic alterations in FGFR2/3, but the activity of EV in this subset is unclear. We investigated the activity of EV in patients (pts) with mUC based on FGFR2/3 genotype to inform management. Methods: In this multi-center, retrospective analysis, we assessed the objective response rate (ORR) to EV in mUC pts with and without FGFR2/3 genomic alterations detected by targeted panel next-generation sequencing. Activating gene fusions and known hotspots mutations in the two genes were considered. Descriptive analysis of ORR and patient characteristics was performed. Fisher’s exact test and binomial test with two-tailed p-value were used. Results: 40 pts were available from 4 institutions. Most pts were male (31/40, 78%) and the median age at start of EV was 74.1 (range 49 – 90) years. Ten patients (25%) had upper tract urothelial carcinoma (UTUC), and 33 (82%) had baseline ECOG performance status of 0-1. 31 of 39 patients had received both platinum-based chemotherapy and PD1/L1 inhibitors. Seven patients had confirmed activating hotspot FGFR3 mutations (p.S249C or p.Y373C). One pt had FGFR2 high-level amplification (HA), and one had FGFR3 HA. Of 36 patients evaluable for ORR, 18 had partial response (PR), 12 had stable disease (SD) and 6 had progressive disease (PD). Patients with FGFR2/3 activating mutations exhibited an ORR that was not statistically different compared to patients without no mutations: 2/7 (29%; 90% CI: 5 – 66%) vs. 16/29 (55%; 90% CI: 38 – 71%) respectively ( p-value = 0.4). 3/7 patients with FGFR3 hotspot mutations received an FGFR2/3 inhibitor and none responded; one of them had a sequential response to EV. Conclusions: In this multi-center retrospective cohort, FGFR2/3 activating genomic alterations did not appear to compromise response to EV in mUC. Larger studies are required to confirm our findings and optimal sequencing of EV and erdafitinib in mUC pts with FGFR2/3 genomic alterations requires further assessment.

489 Background: Immune checkpoint inhibition (ICI) has greatly improved clinical outcomes for pts with mUC and other cancers. ICI is associated with a class of AEs, deemed irAEs due to immune activation. Nonetheless, biomarkers associated with irAE are still lacking. We hypothesized that the immune response against neoantigens is partly responsible for irAEs and investigated the association between irAEs, TMB and response to ICI. Methods: We identified patients with mUC at Dana Farber Cancer Institute who were treated with ICI (monotherapy or combination) and had available tumor sequencing data through Oncopanel. TMB was calculated using the number of non-synonymous exonic mutations per megabase. The severity of irAEs was graded using CTCAE v.5.0. Mann-Whitney U test was performed to identify association between TMB, incidence and grade of irAEs. A cut-off of 10/mb was assigned for TMB. Fisher’s exact test was used to evaluate the radiologic response between pts with and without irAEs and low vs. high TMB. Multivariable linear regression was used to assess the relationship between TMB, irAEs and response. p-values were adjusted using Benjamini-Hochberg method. Results: Of 101 pts with mUC who met the inclusion criteria, 32 (32%) reported irAEs. 6 (6%) were grade (G)1, 20 (20%) were G2, and 6 (6%) were G3. Median(m) time on therapy was 84 days for pts without irAEs and 88 days for pts with irAEs. Pts with irAEs had higher mTMB (15.4/mb) compared to pts with no irAEs (9.8) ( p = 0.01). In pts on monotherapy (93), those with irAEs (n=27) had a higher mTMB (15.13/mb) compared to pts with no irAEs (n=66) (mTMB = 10.20/mb) ( p = 0.01). Out of 94 pts with radiological data, response was achieved in 16 (50%) pts with irAE vs 10 (16%) pts with no irAE ( p < 0.001). When both irAE and response were included in a multivariable regression, the association between irAE and TMB was not significant ( p = 0.4). Pts with both irAE and high TMB had a response rate of 56% which was significantly higher than those with either irAE but low TMB (28.6%) or high TMB but no irAE (21.2 %) or low TMB and no irAE (10.3%) (Chi-square test p = 0.002; FDR corrected p-values for individual comparisons in Table). There was no association between TMB and irAE grade. Conclusions: Higher TMB was associated with higher incidence of irAEs in pts with mUC on ICIs. Moreover, pts with both high TMB and irAEs exhibited better response rates than those with only high TMB or irAEs, suggesting that they may provide complementary tumor and host characteristics. Further evaluation in mUC is needed to confirm this relationship between TMB, irAEs and response in a larger cohort and explore specific mutational signatures that may be associated with irAEs. [Table: see text]

467 Background: The genetics of urothelial carcinoma (UC), the most common histology of urinary tract (UT) tumors, is well characterized; much less is known about the genomic features of rare histologic variants of UT tumors. We aim to compare the genomic alterations (GA) of UT tumors with adenocarcinoma (AD), small cell (SC), squamous cell (SQ), or plasmacytoid (PC) histologies, to UC tumors. Methods: We identified patients with pure variant (AD, SC, SQ, PC) or UC histology with genetic characterization through the GENIE registry. Patient tumor genomic data were captured by Memorial Sloan Kettering Cancer Center (MSK)-IMPACT and Dana-Farber Cancer Institute (DFCI)-Oncopanel NGS initiatives. Tumors with mixed histology were excluded. We limited our analysis to genes tested >1000 times (N=211). Mutation frequencies and copy number variants (CNVs), collectively called GAs, were determined for AD, SC, SQ, PC, and UC, and were compared using the Fisher’s Exact test and Kruskall Wallis test. Nominal p values were obtained, and FDR correction was employed (q < 0.1). Results: We identified 1199 patients with available genomic data who met the inclusion criteria. Histologic distribution was: 32 AD, 13 SC, 15 SQ, 11 PC, and 1128 UC tumors. The median age was 68 years and 77% of patients were male. Statistically significant differences in genetic alterations by subtype are shown in the table below. ARID1A and KDM6A GAs were higher in UC; PC and SC; CDH1 GAs higher in PC; RB1 and TP53 GAs higher in SC; SMAD4 GAs higher in AD; and NFE2L2 GAs higher in SQ. Conclusions: Variant UT histologies exhibit a distinct pattern of alterations compared to UC, consistent with their divergent clinical behavior. This suggests different biological origins for these variant histologies and possibly different therapeutic vulnerabilities. Exploring the GAs of these UT tumors in larger datasets is warranted. [Table: see text]

432 Background: The renin-angiotensin system (RAS) is involved in regulation of angiogenesis, cell proliferation, desmoplasia and immunosuppression. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) may have antitumor effects partly by inhibiting transforming growth factor (TGF)-β, a major resistance mechanism in bladder cancer. Methods: Patients (pts) with muscle invasive bladder cancer (MIBC) treated or not treated with ACEi/ARB while receiving preceding radical cystectomy (RC) were assessed for pathologic complete response (pCR) defined as pT0N0 and overall survival (OS). Pathologic features, performance status, clinical stage, type and number of cycles of NAC, and presence of grade ≥3 toxicities were collected retrospectively. The Kaplan-Meier method was used to estimate overall survival (OS). Logistic and Cox regression was used to explore factors potentially prognostic for pCR and OS respectively. Results: 187 patients received NAC followed by RC. The mean age at the time of NAC was 65. 71% were male and 29% were female. Of the 187 patients, 61% received Cisplatin/Gemcitabine and 28.3% received dose dense MVAC. Of patients receiving NAC, 53 (28%) had a pCR. The 5-year OS was 64%. There were 41 (21.9%) patients taking an ACEi and 24 (12.8%) patients taking an ARB at the start of NAC. Of the 41 patients who took an ACEi, 17 (41.5%) had a pCR; of the 146 patients who did not take an ACEi, 36 (24.7%) had a pCR. ACEi intake during NAC was the only factor associated with pCR on multivariable analysis (odds ratio of 2.17 [95% CI 1.05-4.48] p = 0.037). pCR was the only factor shown to be associated with significantly improved OS (Hazard Ratio 0.18 [95% CI 0.07-0.45] p = < 0.001). After adjusting for pCR, ACEi was not significantly prognostic of OS (HR = 1.12, 95% CI = 0.60 to 2.09, p = 0.72). ARB intake while receiving NAC was not associated with pCR or OS. Conclusions: ACEi intake was associated with significantly increased pCR in patients with MIBC receiving NAC, and pCR was the only significant factor associated with OS. We hypothesize that ACEi may augment the activity of NAC and increase pCR, which translates to improved OS. ACEi intake was not associated with improvement in OS potentially due to competing causes of mortality in patients requiring ACEi. Our data requires validation.

10043 Background: We previously defined a novel outcome, TFS, to characterize the time between ICI therapy cessation and subsequent therapy initiation/death. TFS is part of an integrated analysis to comprehensively describe how pts spend overall survival (OS) time, on and off treatment, with/without treatment-related toxicity. We reported survival states, including TFS, in ICI-treated pts with MEL in the phase 3 CheckMate 067 trial (NCT01844505) over the 36-mo period since randomization (Regan. J Clin Oncol. 2019); 60-mo results are presented here. Methods: Data were analyzed for 937 pts with MEL who started treatment with nivolumab (NIVO) plus ipilimumab (IPI), NIVO, or IPI in CheckMate 067. TFS was defined as the area between the Kaplan–Meier (KM) curves for 2 conventional time-to-event endpoints defined from randomization: time to protocol therapy cessation and time to subsequent therapy/death. TFS was also divided into TFS with/without grade ≥3 treatment-related adverse events (TRAEs), and OS was estimated. The area under each KM curve was estimated by the 60-mo restricted mean (r-mean) time to event and expressed as a percentage of the 60-mo period. Bootstrapped 95% CIs were calculated for differences. Results: Over the 60-mo period, pts spent an average of 33%, 17%, and 20% of time free of treatment after receiving NIVO+IPI, NIVO, and IPI, respectively (r-mean TFS, 19.7, 9.9, and 11.9 mo; Table). NIVO+IPI-treated pts had r-mean TFS that was 9.8 mo longer than NIVO-treated pts (95% CI, 6.7–12.8) and 7.8 mo longer than IPI-treated pts (95% CI, 4.6–11.0). Mean TFS with grade ≥3 TRAEs remained a small proportion of the 60-mo period at 3%, 2%, and < 1% with NIVO+IPI, NIVO, and IPI, respectively. Conclusions: With extended follow-up, average TFS with/without toxicity represented greater percentages of the 60-mo vs 36-mo period for NIVO+IPI and NIVO, but not for IPI. Pts treated with NIVO+IPI continued to have TFS twice as long as those treated with NIVO alone, due to earlier therapy cessation for toxicity without disease progression and subsequent resolution of many of those toxicities. The majority of TFS time was spent without grade ≥3 TRAEs across all arms. [Table: see text]

Background Conventional measures such as median progression-free survival may suboptimally characterize the full impact of immuno-oncology (I-O) agents vs other systemic anticancer therapies. Patients discontinuing I-O agents may experience periods of disease control without needing subsequent systemic anticancer therapy (Rx) but may still experience toxicity (TOX). Treatment-free survival (TFS) ± TOX can simultaneously characterize disease control and TOX for this off-treatment period. Methods Data were analyzed from all 1082 patients initiating Rx on the randomized phase 3 CheckMate 214 trial of nivolumab + ipilimumab (NIVO+IPI) vs sunitinib (SUN) for treatment-naive predominantly clear cell advanced renal cell carcinoma. TFS is defined as the area between Kaplan–Meier (KM) curves for 2 conventional time-to-event endpoints defined from randomization: time to protocol Rx cessation and time to subsequent Rx or death. TFS was subdivided as TFS with and without TOX by defining a third endpoint: time to cessation of Rx and TOX. TOX was defined as grade ≥3 Rx-related adverse events. Area under each KM curve was estimated by the 36-month restricted mean time to event. Results At 36 months, 60% of NIVO+IPI and 51% of SUN patients were alive, 15% NIVO+IPI and 9% SUN remained on original Rx, and 34% NIVO+IPI and 19% SUN patients were surviving free of subsequent Rx. The 36-month restricted mean TFS was 6.7 and 2.9 months for all NIVO+IPI and SUN patients, respectively (6.4 vs 2.8 months TFS without TOX). The table shows time by TFS subdivision and IMDC risk. Table . 971P IMDC risk group All Favorable Intermediate/Poor N = 547 N = 535 N = 124 N = 119 N = 423 N = 416 Restricted mean time NIVO+IPI SUN Difference NIVO+IPI SUN Difference NIVO+IPI SUN Difference OS, months 28.0 25.6 32.0 32.9 26.9 23.5 Time on protocol Rx, months 13.4 12.7 13.5 20.1 13.4 10.6 TFS, months (95% CI) 6.7 2.9 3.8 (2.4–5.3) 9.8 2.7 7.2 (4.4–10.0) 5.8 3.0 2.8 (1.7–4.0) TFS with TOX 0.4 0.1 0.2 (0.05–0.4) 0.5 0.1 0.4 (0.2–0.6) 0.3 0.2 –0.1 (–0.03–0.3) TFS without TOX 6.4 2.8 3.6 (2.3–5.0) 9.4 2.6 6.8 (4.1–9.5) 5.5 2.8 2.7 (1.6–3.8) Survival after subsequent Rx initiation, months 7.9 10.0 8.7 10.2 7.7 10.0 IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; OS, overall survival. Conclusions NIVO+IPI provides longer survival and delayed time to subsequent Rx vs SUN. More importantly, NIVO+IPI provides longer TFS without TOX, during which patients do not require Rx and are free from TOX. Given the durability of I-O responses relative to SUN after Rx cessation, it will be of interest to measure TFS over time. Clinical trial identification NCT02231749. Editorial acknowledgement Nicolette Belletier, PhD, and Lawrence Hargett of Parexel. Legal entity responsible for the study Bristol-Myers Squibb. Funding Bristol-Myers Squibb and ONO Pharmaceutical Company Limited. Disclosure M.M. Regan: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): IPSEN; Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Veridex; Research grant / Funding (institution): OncoGenex; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Ferring; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pierre Fabre; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Millennium Pharmaceuticals; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Sotio; Research grant / Funding (institution): Dendreon; Research grant / Funding (institution): Medivation. M.B. Atkins: Honoraria (self), Advisory / Consultancy: BMS; Advisory / Consultancy: Genentech; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: X4 Pharma; Advisory / Consultancy: Merck; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Acceleron; Advisory / Consultancy: Eisai; Advisory / Consultancy: Glactone Pharma; Advisory / Consultancy: Agenus; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Aduro Biotech; Advisory / Consultancy: Newlink Genetics/Pharmatech; Advisory / Consultancy: Arrowhead Pharmaceuticals; Advisory / Consultancy: Werewolf Pharma; Advisory / Consultancy: Oncolys BioPharma; Advisory / Consultancy: Surface; Advisory / Consultancy: Iovance Biotherapeutics. T. Powles: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self): Merck; Honoraria (self): BMS; Honoraria (self): Pfizer; Honoraria (self): IPSEN; Honoraria (self): Novartis; Honoraria (self): Exelixis. S. Yang: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. J.L. Johansen: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. S. Rao: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. K.M. Gooden: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. D.F. McDermott: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: X4 Pharma; Advisory / Consultancy: Array Biophrama; Advisory / Consultancy, Research grant / Funding (institution): Peloton Therapeutics; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Jounce Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Alkermes; Advisory / Consultancy: Lilly; Full / Part-time employment: BIDMC; Research grant / Funding (institution): Promethus Laboratories. All other authors have declared no conflicts of interest.

Introduction Both venous thromboembolism (VTE) and intracranial hemorrhage (ICH) are common potentially life-threatening complications of primary and metastatic brain tumors. Despite emerging evidence regarding the safety of anticoagulation in patients with brain tumors, there is little evidence on appropriate management of VTE following an ICH. Potential management options after an ICH in patients with brain tumors include resumption of full or modified dose anticoagulation or cessation of anticoagulant therapy with or without placement of an inferior vena cava (IVC) filter. We evaluated rates of recurrent VTE and ICH following an initial ICH occurring on anticoagulant therapy. Methods A retrospective cohort study was performed using a hospital-based online medical record database (CQ2) which links ICD-9 and ICD-10 codes with prescription medication records. Cases were identified based on coding for primary brain tumors or brain metastases, after which charts were manually reviewed for a diagnosis of ICH. A blinded review of radiographic imaging was performed, and the initial ICH was categorized as either trace, measurable, or major. Measurable intracranial hemorrhages were those defined as greater than 1 mL in volume and major intracranial hemorrhages were defined as greater than 10 mL in volume, symptomatic, or requiring surgical intervention. The electronic medical record was reviewed to ascertain longitudinal anticoagulation status after the initial ICH. The primary endpoints of the study were recurrent ICH and venous thromboembolism (VTE) within 12 months from the initial ICH. Gray's test was used to compare the cumulative incidence of recurrent ICH and VTE between the groups, with death as a competing risk. Results A total of 79 patients with primary brain tumors or brain metastases and confirmed ICH were included in the study. Fifty-four patients (68.4%) restarted anticoagulation after ICH and 25 patients discontinued anticoagulation entirely. The cohorts were well-matched for tumor diagnosis, age, and comorbidities that portend an increased risk of ICH such as hypertension, chronic kidney disease, and concomitant aspirin use (Table 1). The cumulative incidence of recurrent ICH (95% CI) at one year was 6.1% (1.5 - 15.3) in the restart cohort compared to 4.2% (0.3 - 18.3) in patients who did not restart anticoagulation. Median time from anticoagulation restart to recurrent ICH was 36 days. A total of 16 of 31 patients with major ICH restarted anticoagulation and among these patients two developed subsequent ICH (cumulative incidence 14.5%, 95% CI 2.1 - 38.3). Among the 15 patients with a major ICH who did not restart anticoagulation, the cumulative incidence was 6.7% (0.3 - 27.5). Eleven of 15 patients with measurable ICH restarted anticoagulation and among these patients one subsequently developed ICH (cumulative incidence 0.1%, 95% CI 0.0 - 0.3). No recurrent ICH events were observed in 33 patients with trace initial hemorrhages regardless of restart status. All recurrent ICH events met criteria for classification as a major hemorrhage on the basis of clinical symptoms, and 30-day mortality after recurrent ICH was 100%. The cumulative incidence of recurrent VTE was significantly lower in the restart cohort compared to cohort of patients who did not restart anticoagulation (8.1 vs. 35.3, P=0.003, Figure 1). There were a total of five VTE events in the restart cohort, three deep vein thrombi (DVT) and two pulmonary emboli (PE). Two of the DVT were associated with an IVC filter. There were a total of nine VTE events in patients who did not restart anticoagulation, seven DVT and two PE. Five of the DVT were associated with an IVC filter. The two PE were both submassive events requiring ICU admission. Conclusions Recurrent VTE events are less frequent and less severe in patients who restart anticoagulation following ICH in patients with brain tumors on anticoagulation. Restarting anticoagulation after smaller ICH (trace or measurable) appears safe. However, approximately 1 in 7 patients with major initial ICH who restarted anticoagulation subsequently developed recurrent major ICH that was associated with a very high mortality rate. This raises serious questions as to the safety of restarting therapeutic anticoagulation following major hemorrhage in the setting of brain tumors. Disclosures Neuberg: Pharmacyclics: Research Funding; Madrigal Pharmaceuticals: Equity Ownership; Celgene: Research Funding. Zwicker:Quercegen: Research Funding; Daiichi: Consultancy; Seattle Genetics: Consultancy; Parexel: Consultancy; Incyte: Research Funding; Bayer: Consultancy; Portola: Consultancy.

9550 Background: Many pts treated with ICIs can discontinue treatment and experience ongoing disease control and toxicity. We previously proposed a novel outcome, TFS, as the time between ICI therapy cessation and subsequent therapy initiation or death, with integrated graphical analysis to better characterize the unique effects of ICIs (ASCO 2018 #9531). In the CheckMate 067 and 069 trials of ipilimumab (IPI) and nivolumab (NIVO) alone or in combination (NIVO+IPI) in pts with MEL, the 36-month restricted mean TFS was 8.7, 4.6 and 11.1 mo, respectively. We explored the sensitivity of TFS to be informative of overall survival (OS) differences through subgroup analysis. Methods: Data from MEL pts in the CheckMate 067 and 069 trials were pooled and analyzed. TFS was defined as the area between the Kaplan-Meier curves for two endpoints, from randomization: (A) time to ICI therapy cessation; and (B) time to subsequent therapy initiation or death. TFS was estimated by restricted mean survival time until 36 mo since randomization. Differences in restricted mean TFS between subgroups of pts (such as PD-L1 status, lactate dehydrogenase [LDH], performance status [PS], gender) were calculated with bootstrapped 95% CIs. OS from randomization was also estimated. Results: Among 407 pts treated with NIVO+IPI, restricted mean TFS ranged from 8-13 mo across subgroups (Table). Subgroup differences in mean TFS were larger for prognostic factors LDH and PS and smaller in non-prognostic PD-L1 status and gender subgroups. Conclusions: Clinically meaningful TFS was seen across all subgroups. TFS was sensitive to prognostic subgroup differences. These results provide further support for TFS as a relevant clinical endpoint. Additional subgroups and comparisons with single agent NIVO and IPI arms will be presented at the meeting. [Table: see text]

4582 Background: CD73 or ecto-5'-nucleotidase mediates the de-phosphorylation of adenosine monophosphate to adenosine which promotes immunosuppression in the tumor microenvironment. Its prognostic significance in localized RCC has not been well characterized. Methods: We assessed CD73 protein expression using immunohistochemistry (Cell Signaling Technology, D7F9A, 1:25) on tissue microarrays (TMAs) containing tumor tissue from patients with pT1-4,N0-1, M0 RCC who underwent nephrectomy.CD73 expression was quantified using a combined score (CS: intensity x percentage of cells staining positive). CD73 positivity was defined as any CD73 expression on tumor cells (CS > 0). Patients were categorized into CD73 negative (CS = 0), low ( < median CS) and high (≥ median CS) groups. Clinical data was collected retrospectively.Baseline patient characteristics were compared between CD73 negative and positive (high + low) groups using the Cochran-Armitage trend test. Multivariable Cox regression evaluated associations of CD73 expression with disease-free and overall survival (DFS, OS) after adjusting for other baseline prognostic variables. Results: Of the 112 patients included, clear cell was the most common histology (70%) followed by chromophobe (12.5%), and papillary (12%) RCC. CD73 expression (CS > 0) was noted in 22% (n = 25) of tumors and was associated with more advanced stage (T3-4/N+: 37.5% vs. 25%; p = 0.02) and a trend towards higher nuclear grade (≥3: 48% vs. 35%; p = 0.07). Median follow-up from nephrectomy was 9.7 yrs. In multivariable analysis adjusting for nuclear grade ( < 3 vs. ≥3) and stage (T1-2, N0 vs. T3-4/N+), tumors with high CD73 expression had significantly worse DFS and OS (Table). Conclusions: CD73 expression was found in 22% of RCC patients and was associated with adverse pathologic features and poor prognosis independent of tumor stage and histologic grade. Our results provide strong rationale for further investigation of the CD73/adenosine pathway as a therapeutic target in RCC. [Table: see text]

Introduction Venous thromboembolism (VTE) is a common complication of cancer. Patients with primary brain tumors and brain metastases are at particularly high risk, with about 20-30% suffering a VTE event. The administration of enoxaparin appears to be safe in patients with brain metastases but confers an increased risk of intracranial hemorrhage (ICH) in patients with primary brain tumors. Direct-acting oral anticoagulants (DOACs) have demonstrated efficacy in the treatment of cancer-associated thrombosis with an increased risk of hemorrhage compared to low molecular weight heparin (LMWH). There are limited data on the safety of DOACs in patients with brain tumors. As the risk of ICH associated with parenteral anticoagulants differs for primary versus secondary brain tumors, we analyzed ICH outcomes for patients with VTE receiving enoxaparin or a DOAC. Methods A retrospective cohort study was performed using a hospital-based online medical record database (CQ2) linking ICD-9 and ICD-10 codes with prescription medication records. Cases were identified based on coding for primary brain tumors or brain metastases and prescription of either a DOAC or enoxaparin. A blinded review of radiographic imaging was performed, and intracranial hemorrhages were categorized as either trace, measurable, and major. Measurable intracranial hemorrhages were those defined as greater than 1 mL in volume and major intracranial hemorrhages were defined as greater than 10 mL in volume, symptomatic (defined as focal deficit, headache, nausea, or a change in cognitive function), or required surgical intervention. Gray's test was used to compare the cumulative incidence of ICH between the groups, with death as a competing risk. Results A total of 170 patients with primary brain tumors and brain metastases were included in the study. In the primary brain tumor cohort (N=65), 18 patients received a DOAC while 47 received enoxaparin. The cumulative incidence of any ICH at 12 months was 0% in patients receiving a DOAC compared to 36.8% (95% confidence interval 22.3-51.3%) in those receiving enoxaparin (P=0.012). There were no major ICH events in the DOAC group and 8 and in the LMWH group (12-month cumulative incidence of 0% versus 18.2%, 95% CI 8.4-31.0, P=0.062). In the brain metastases cohort (N=105), 21 patients received a DOAC while 84 received enoxaparin. The DOAC and enoxaparin groups were well-matched for tumor diagnosis (non-small lung cancer 52% and 51%, respectively) including those tumor types with a high incidence of ICH (i.e. melanoma 5% and 7% and renal cell carcinoma 14% and 11%, respectively). In patients with brain metastases, DOACs did not increase the risk of any ICH relative to enoxaparin (12-month cumulative incidence 27.8% versus 52.9%, P=0.15) nor major ICH (12-month cumulative incidence 11.1% vs 17.8%, P=0.38). Conclusions DOACs can be safely administered to patients with brain tumors. In patients with primary brain tumors (i.e. glioma), DOACs appear to be safer than LMWH and should be considered for this indication. Figure. Figure. Disclosures Zwicker: Incyte: Research Funding; Parexel: Consultancy; Quercegen: Research Funding; Daiichi: Honoraria.

299 Background: Advance care planning is an important aspect of providing high quality care to oncology patients. ASCO Quality Oncology Practice Initiative (QOPI) recognizes the importance of advance directive documentation as a quality measure. MOLST forms are often completed to document a patient’s preferences for medical care at the end of life. The primary objective of this study was to improve the MOLST form documentation process in an outpatient solid tumor oncology clinic. Methods: We conducted a survey to identify areas for improvement and created a process map illustrating the complexities of the current MOLST form documentation process. A multidisciplinary team comprised of physicians, nurses, administrative staff, a quality improvement leader and a palliative care expert was created to focus on this initiative. We developed a new process whereby completed MOLST forms were uploaded into the electronic medical record (EMR) system. We implemented the following interventions: 1) made MOLST forms accessible to clinicians; 2) created a centralized location to place MOLST forms; 3) educated oncology staff about the new process; and 4) streamlined the MOLST form scanning process into the EMR. This process was studied during a pilot between January 22, 2018-February 2, 2018. A pre-pilot convenience sample was compared to pilot data. Results: Oncologists identified the need to improve the MOLST form documentation process on the pre-pilot survey. The percentage of completed MOLST forms scanned into the EMR increased from 44.4% (4 out of 9 forms) pre-pilot to 87.5% (7 out of 8 forms) during the pilot (p = 0.06). All of the MOLST forms completed using the new process were scanned into the EMR. Physician satisfaction with the MOLST process increased from 7.1% (2 out of 28 survey respondents) pre-pilot to 87.5% (14 out of 16 survey respondents) post-pilot (p < 0.01). Conclusions: A targeted process to enhance the documentation of completed MOLST forms succeeded and increased physician satisfaction. Further work will need to be performed to better identify oncology patients appropriate for MOLST form discussions.

BACKGROUND Venous thromboembolism occurs in approximately 15-30% of individuals with primary brain tumors (e.g. glioblastoma, astrocytoma, and oligodendroglioma). Spontaneous intracranial hemorrhage (ICH) is also a frequent complication of primary brain tumors thus complicating the decision to administer therapeutic anticoagulation. Therapeutic anticoagulation does not appear to increase the risk of intracranial hemorrhage among patients with solid tumor brain metastases but whether anticoagulation is safe to administer to patients with primary brain tumors is less clear. The aim of this study was to determine the rate of intracranial hemorrhage associated with therapeutic enoxaparin for treatment of venous thromboembolism in patients with primary brain tumors compared to those patients with brain tumors not exposed to therapeutic anticoagulation. METHODS A 1:1 matched, cohort study was performed using a large hospital-based online medical record database (CQ2) linking ICD-9 codes with prescription medication records, cases were initially identified based on coding for primary brain tumors, venous thromboembolism, and prescription of enoxaparin. Matched controls were identified using a "round-robin" algorithm that ranked controls according to a scoring formula based on successful match for year of diagnosis, age, and gender. A blinded review of radiographic imaging was performed and intracranial hemorrhages were categorized as trace, measurable, and significant. Measurable intracranial hemorrhages were those defined as greater than 1 mL in volume and "significant" intracranial hemorrhages were defined as greater than 10 mL in volume, symptomatic (defined as focal neurologic deficit, headache, nausea, or change in cognitive function), or required surgical intervention. Time-to-event statistical analysis was performed using a competing risk analysis to account for death from any cause as an absorbing competing risk. Statistical comparison of event rates between cases and controls was performed using Fine and Gray competing risk regression. RESULTS A total of 100 patients with primary brain tumors were included in the study. The most common diagnosis was glioblastoma (85%), followed by anaplastic oligodendroglioma (8%), and anaplastic astrocytoma (7%). The two cohorts were well matched for age (60 years old), gender (65% male), and types of treatment received (99% radiation, 34% stereotactic radiosurgery, and 71% surgical resection). There was no statistical difference in the rate of measurable intracranial hemorrhage for the group of patients who received therapeutic enoxaparin at any point following the diagnosis of glioma compared to those who did not receive anticoagulation (subdistribution ratio hazard ratio 1.09, 95% CI 0.53-2.22). The 1-year cumulative incidence of measurable hemorrhage among those who were treated with enoxaparin was 23.6% compared with 20.0% in the control group (Gray's test P=0.48). The 1-year cumulative incidence of significant hemorrhage was 13.1% in those receiving enoxaparin compared with 6.0% in controls (sHR 1.45, 95% CI .47-4.65, P=0.68). The median survival was similar for the enoxaparin (1.56 years) and controls (1.63 years, Log rank P=0.81). CONCLUSION Intracranial hemorrhage is common in patients with primary brain tumors. In this matched cohort analysis utilizing a blinded radiologic review, the administration of therapeutic low molecular weight heparin did not significantly increase the risk of intracranial hemorrhage in the setting of glioma and venous thromboembolism. In patients with primary brain tumors, the diagnosis of venous thromboembolism treated with therapeutic enoxaparin did not impact overall survival. Disclosures Zwicker: Quercegen Pharma: Research Funding.