e23088 Background: Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment landscape for relapsed or refractory hematologic malignancies. National data comparing inpatient outcomes among different CAR-T products is limited. The CMS introduced ICD10-PCS procedure codes for individual CAR-T products that went into effect on October 1st, 2021. Leveraging these codes, we conducted a national analysis of real-world inpatient outcomes associated with FDA-approved CAR-T therapies in 2023. Methods: We conducted a retrospective cross-sectional study using the 2023 Healthcare Cost and Utilization Project National Inpatient Sample. Hospitalizations involving CAR-T therapy were identified using ICD-10-PCS procedure codes. The primary outcome was a composite measure of severe inpatient toxicity, defined as the occurrence of any of the following: in-hospital mortality, mechanical ventilation, clinically significant cytokine release syndrome (CRS), or clinically significant immune effector cell-associated neurotoxicity syndrome (ICANS). Secondary outcomes included individual components of the composite, and tumor lysis syndrome (TLS). National estimates were generated using discharge-level survey weights. Pairwise comparisons were performed using the Rao-Scott chi-square test with Bonferroni correction for multiple comparisons. Statistical analysis was conducted using the SAS software (SAS Institute, Cary, NC). Results: A total of 1,117 (weighted N = 5,585) inpatient CAR-T hospitalizations occurred nationally in 2023. The mean age was 61 years with 62% being male. Underlying indications included Large B-Cell Lymphoma (40%), Multiple Myeloma (28.9%), Acute Lymphoblastic Leukemia (7.3%) and other hematologic malignancies. The composite severe toxicity outcome occurred in 27.8% of hospitalizations. Clinically significant CRS and clinically significant ICANS occurred in 18.1% and 14.8%, respectively, while 2.1% required mechanical ventilation and TLS occurred in 1.6% of hospitalizations. The in-hospital mortality rate was 1.9%. Compared with Axi-cel, Cilta-cel (aOR 0.51), Ide-cel (aOR 0.50), and Liso-cel (aOR 0.59) were associated with significantly lower odds of the composite outcome (p < 0.01). Compared with Axi-cel, Cilta-cel (aOR 0.15), Ide-cel (aOR 0.30), and Liso-cel (aOR 0.33) were associated with significantly lower odds of ICANS (p < 0.01). Conclusions: In this national analysis of CAR-T hospitalizations, substantial heterogeneity in severe toxicity and neurotoxicity was observed across FDA-approved CAR-T products. Compared with Axi-cel, several newer CAR-T therapies were associated with significantly lower odds of severe toxicity and neurotoxicity in real-world practice, highlighting important product-specific differences that may inform risk stratification and clinical decision making.

2556 Background: Chimeric antigen receptor T-cell [CART] therapy has marked a new era in the treatment of relapsed/refractory hematological malignancies since its approval in 2017. Racial disparity was studies previously but not gender. Current study aimed to evaluate gender disparity in CART therapy utilization and outcomes. Methods: This cross sectional study was done using National Inpatient Sample [NIS], the largest database available in the US. Inpatient admissions of adults who received CART therapy for various indications during year 2020 were included. Results: A total of 6915 patients were admitted to hospital for CART therapy in 2020 with an overall inpatient mortality rate of 1%. Mean age of the patients was 57yr. Majority were White [64%], with a higher median household income, admitted to urban and large sized hospitals and predominantly covered by Medicare or private insurance [~80%]. Study population was divided into males and females and outcomes were compared. Females were significantly younger with lower Charlson comorbidity index and higher utilization of CART therapy [81% vs 19%] compared to males. Females had 86% lesser odds of mortality compared to males (Odds Ratio [OR] 0.14; 95% confidence interval [CI] 0.04-0.47; p value 0.001). Females had significantly lesser hospitalization charges [mean decrease $471,193; p value 0.000] and length of stay [mean decrease 8 days; p value 0.000] compared to males after adjusting for confounders. Racial differences in outcome were compared after multiple imputation was used to correct for 4% missing data in the race category in NIS 2020. There was no statistically significant difference in mortality, length of stay or hospitalization charges between Whites, Blacks and Hispanic races similar to previous studies. Conclusions: Eligibility criteria for CART therapy includes patients with good performance status and organ function with less comorbidities. Our study found that females were younger, healthier and therefore qualified better for CART therapy compared to males. Hence they had significantly higher utilization of CART therapy. In addition, among the population receiving CART therapy, females had better outcomes compared to males in terms of mortality, length of stay and hospitalization charges. In general, males have higher incidence and mortality with poorer outcomes in most hematological malignancies where CART therapy is a treatment option. Measures at modifying and improvising CART therapy to cater to more male subjects will not only reduce gender disparity but also improve overall survival and reduce disease burden. [Table: see text]

6581 Background: Thrombotic complications are a well known cause of morbidity and mortality in Philadelphia-negative Myeloproliferative Neoplasms[Polycythemia Vera, Essential thrombocythemia, Primary Myelofibrosis]. Current study evaluated thrombotic events incidence and outcome trends in Myeloproliferative Neoplasms[MPN] from 2012 to 2020. Methods: This is a longitudinal study of thrombotic events in MPN using the Nationwide Inpatient Sample. All patients with a diagnosis of MPN admitted with any thrombotic event including arterial or venous thrombosis were included in the study. Arterial thrombotic events included Myocardial infarction[MI], Ischemic stroke[IS], Transient Ischemic Attack[TIA] while venous thrombotic events included Deep Vein Thrombosis[DVT], Pulmonary Embolism[PE], Budd-Chiari Syndrome[BCS], Portal Vein Thrombosis[PVT]. Thrombosis related inpatient mortality rate, incidence, length of hospital stay, and total hospital charges were calculated. Results: Mortality rate from any thrombotic event overall[arterial plus venous] increased from 2.3% to 2.6% from 2012 to 2020. There was an increase in mortality rates from 2.8% to 3.8% among arterial thrombosis while there was a decrease in venous thrombosis related mortality from 1.7 to 0.4%. Specifically MI and IS related mortality increased from 3.7% to 4.3% and 3% to 4% respectively over the same period. The incidence of any thrombotic event declined from 2 to 1.3 cases/100,000 persons from 2012 to 2020. A similar decline in incidence of arterial, venous events, MI, IS were observed. The mean length of stay decreased from 5.8 days in 2012 to 5.2 days in 2020 among MPN patients with venous thrombosis which was statistically significant. Similar decline was noted in MI patients as well. Though the mean length of stay increased from 7.9 to 9.5 days among MPN patients with IS, this increase was not statistically significant. The mean hospitalization charges for thrombotic events increased from $53,421 in 2012 to $101,598 in 2020 after adjusting for inflation. Similar trends were noted in all types of thrombotic admissions which were all statistically significant. Upon age based stratification of MPN, mortality for those less than 60 years reduced from 2% to 0.3%, while it increased from 4.1 to 5.6% in those more than 60 years from 2012 to 2020. Conclusions: Inpatient mortality from thrombotic events in MPN has shown an increasing trend from 2012 to 2020 though there was a decline in overall incidence of thrombosis during the same period. Despite the decreasing trend in length of stay, the total economic burden of thrombotic complications in MPN is increasing in the US. Specifically the effects were more pronounced in those greater than 60 years. This points to the need for revisiting guidelines regarding thromboprophylaxis in MPN.

8504 Background: In unselected patients (pts) with extensive-stage small cell lung cancer (ES-SCLC), the addition of immune checkpoint inhibitors (ICI) to chemotherapy resulted in a modest improvement in OS. In a retrospective analysis of a study with veliparib (PARP inhibitor [PARPi]) and temozolomide in patients with SCLC, Schlafen-11 (SLFN11) predicted PFS and OS benefit for the addition of PARPi. We evaluated whether the addition of PARPi (talazoparib) to standard-of-care maintenance ICI (atezolizumab) following frontline chemoimmunotherapy improved outcomes in pts with SLFN11-positive ES-SCLC. Methods: Participants with ES-SCLC expressing SLFN11 (H-score ≥ 1, evaluated centrally at MDACC) were randomized to maintenance atezolizumab (A) versus atezolizumab plus talazoparib (AT) following frontline chemotherapy and A. Randomization was stratified by Zebrod PS (0-1 vs 2) and use of consolidation thoracic radiation. The primary endpoint was PFS, and secondary endpoints included ORR, OS, and toxicity. The primary analysis was done using a 1-sided 10% level stratified log-rank test. Target sample size was 94 pts. Results: From June 2020 to December 2022, 309 pts were screened, of which 204 of 259 (79%) with evaluable tissue were SLFN11 positive, and 106 were randomized (52 A, 54 AT). Median follow up time is 5 months. Median age was 67 (45-84); 51 (48%) were females; 94 (89%) were white,102 (96%) were PS 0-1, and 26 (25%) had radiation prior to randomization. With 80 PFS events reported, PFS was significantly improved with AT (hazard ratio [80% CI]: 0.70 [0.52-0.94]; p = 0.056). Median PFS was 2.8 months (80% CI 2.0-2.9) for A and 4.2 months (80% CI 2.8-4.7) for AT. OS was not different (hazard ratio [80% CI]: 1.17 [0.80-1.71]; p = 0.30). Median OS was 8.5 months (80 % CI 7.4-12.7) for A and 9.4 months (80% CI 8.1-14.2) for AT. ORR was 16% (5/32, 80% CI 8-27%) for A and 12% (4/34, 80% CI 5-22%) for AT. Grade 3 or greater treatment related non-hematological adverse events (AEs) occurred in 13% pts in A and 15% in AT. Hematological AEs occurred 4% in A compared to 50% pts in AT (Expected for T) (p < 0.001). There were no treatment related grade 5 events. One participant on AT experienced grade 3 febrile neutropenia. The majority of grade 3 AEs were due to anemia (2% in A and 37% in AT). Only three pts discontinued treatment due to toxicity (2 in A and 1 in AT). Conclusions: This study met its primary endpoint demonstrating that maintenance AT improved PFS in SLFN11-selected patients with ES-SCLC. Hematologic toxicity was increased with AT as expected, with majority being grade 3 anemia. This study demonstrates the feasibility of conducting biomarker selected trials in SCLC, paving the way for future evaluation of novel therapies in selected SCLC populations. Clinical trial information: NCT04334941 .

PURPOSE To evaluate whether the addition of a poly (ADP-ribose) polymerase inhibitor (PARPi) talazoparib to maintenance immune checkpoint inhibitor (ICI) atezolizumab following frontline chemoimmunotherapy improved outcomes in patients with Schlafen 11 (SLFN11)-positive extensive stage small cell lung cancer (ES-SCLC). METHODS Patients with newly diagnosed SLFN11 expressing (H-score ≥ 1, evaluated centrally) ES-SCLC were randomized to maintenance atezolizumab (A) versus atezolizumab plus talazoparib (AT) following frontline chemotherapy plus atezolizumab. The primary objective was to compare progression-free survival (PFS) using a 1-sided 10% level stratified log-rank test. Secondary endpoints included objective response rate (ORR), overall survival (OS), and toxicity. Target sample size was 84 eligible patients. RESULTS From June 15, 2020 to December 15, 2022, 106 eligible patients were randomized (54 to AT and 52 to A). PFS was improved with AT versus A (hazard ratio [HR], 0.66; 80% confidence interval [CI]: 0.50-0.86; 1-sided P = 0.019) with a median PFS of 2.9 and 2.4 months; OS was not different between groups (HR, 0.98; 80% CI: 0.71-1.36; 1-sided P = 0.47). Grade ≥ 3 non-hematologic treatment-related adverse events (TRAEs) occurred in 17% of patients with AT and 14% of patients with A. Grade ≥ 3 hematological TRAEs were more common in AT (50%) than in A (4%) (P < 0.001). CONCLUSION Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress following initial chemo-immunotherapy. Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected. Prospective biomarker-selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations.

e18869 Background: Acute leukemias are traditionally managed in a hospital setting. During the initial phase of the COVID-19 pandemic, there was a gross shortage of hospital resources and rationing of care. We aimed to study the differences in national trends of hospitalizations and outcomes for acute leukemias in 2019 (pre-pandemic) and 2020 across the United States. Methods: We performed a retrospective study utilizing the National Inpatient Sample (NIS) of adults hospitalized for management of acute leukemias as the primary diagnosis using ICD-10-CM codes. We excluded all patients with a prior or current hospitalization for stem cell transplantation. We compared the outcomes between patients presenting in 2019 (pre-pandemic) and 2020. Outcomes included mortality, length of stay (LOS) and cost of hospitalization. We compared mortality among patients with and without COVID in 2020 using chi-square analysis. Results: Of 166795 admissions for acute leukemia, 71.8% were acute myeloid leukemia (AML), 25.2% were acute lymphoblastic leukemia (ALL) and 3.1% were acute promyelocytic leukemia (APML). Overall, patients were predominantly male (55%), White (68%) presenting to large hospitals (67%) specifically urban teaching hospitals (88%). When compared between 2019 and 2020, there was no difference in the proportion not receiving chemotherapy for their leukemia (77.7% vs 78.6% in 2019 and 2020 respectively). There were no differences between mortality (8.6% vs 8.7%) or median LOS (6 days vs 5 days). The total cost of hospitalization was higher in 2020 ($155,961) compared to 2019 ($151,372). When stratified by COVID-19 infection in 2020, mortality was higher among COVID infected patients in AML (27.5% vs 10.08%, p=0.000), in ALL (16.87% vs 3.30%, p=0.000) as well as APML (26.32% vs 11.5%, p=0.139). Conclusions: Overall, there were no differences in the hospitalizations, rates of chemotherapy administration, mortality or LOS for acute leukemia pre and post COVID-19. However, in 2020, patients with AML and ALL with a concurrent COVID-19 diagnosis had a higher mortality. [Table: see text]

e18799 Background: Neutropenic fever (FN) is an oncologic emergency associated with significant morbidity and mortality. Patients on chemotherapy are at a higher risk of COVID-19-related complications. During the initial phase of the pandemic, healthcare systems were overwhelmed, resulting in shortage of resources and rationing of care. We aimed to assess the impact of the COVID-19 on trends of hospitalization and outcomes in adult emergency department (ED) visits for cancer-related FN in the US between 2019 and 2020. Methods: In this retrospective observational study using the National Emergency Department Sample of adults presenting to ED for cancer-related FN as primary diagnosis (using ICD-10-CM codes), we compared the outcomes between patients presenting in 2019 (pre-pandemic) and 2020. The primary outcome was mortality. Secondary outcomes were incidence of shock, discharge disposition, and length of stay (LOS). A propensity score matching was performed to estimate the effect of COVID-19 on outcomes. Results: There were a total of 95,163 visits to the ED for FN in 2019 and 2020. Both groups had similar demographics, with mainly White (68.1% vs 69.3%) patients presenting to large metropolitan areas (57.6% vs 58.6%) and mostly metropolitan teaching hospitals (74.5% vs 77.2%). More patients presenting in 2020 had a higher Elixhauser comorbidity index (66.6% vs 70.2% for comorbidity of ≥3; p = 0.0002). Although the number of patients who got admitted or died in the ED was similar in 2019 and 2020 (88.4% vs 87.8% for admission and 0.1% for death, p = 0.83), higher number died during their hospitalization (3.4% vs 4.4%, p = 0.002), and were likely to develop shock (6.0 vs 7.1%, p = 0.005) in 2020. More patients were discharged home with services (21.9% vs 17.1%, p < 0.001), while fewer patients went to nursing homes (7.9% vs 8.5%, p < 0.001) in 2020. There were no significant differences in LOS or cost of hospitalization. A propensity score matching was performed to estimate the effect of COVID-19 on outcomes showing higher mortality during hospitalization (13.7% vs 4.6%, p = 0.006) and increased LOS (6 days vs 5 days, p = 0.02) for patients with concurrent COVID-19. Conclusions: Overall, mortality related to FN was higher during the pandemic and more so among patients with concurrent COVID-19. While patients developing shock was higher in 2020, this was not attributable to COVID. Fewer patients were discharged to nursing homes, and more patients went home with services during the pandemic highlighting the constraints imposed on resources during the pandemic. [Table: see text]

Background: On May 28, 2021, the United States Food and Drug Administration (FDA) granted accelerated approval to sotorasib for second-line or later treatment of patients with locally advanced or metastatic KRAS G12C mutant non-small cell lung cancer (NSCLC). This was the first FDA-approved targeted therapy for this patient population. Due to a paucity of real world data describing clinical outcomes in patients with locally advanced or metastatic KRAS G12C mutated NSCLC in the second-line or later, we sought to compile a large, academic medical center-based historical dataset to clarify clinical outcomes in this patient population. Materials and Methods: The clinical outcomes of 396 patients with stage IV (n = 268, 68%) or recurrent, metastatic (n = 128, 32%) KRAS G12C mutant NSCLC were evaluated in this multicenter retrospective chart review conducted through the Academic Thoracic Oncology Medical Investigator's Consortium (ATOMIC). Patients treated at 13 sites in the United States and Canada and diagnosed between 2006 and 2020 (30% 2006-2015, 70% 2016-2020) were included. Primary outcomes included real-world PFS (rwPFS) and overall survival (OS) from time of stage IV or metastatic diagnosis, with particular interest in patients treated with second-line docetaxel-containing regimens, as well as clinical outcomes in the known presence or absence of STK11 or KEAP1 comutations. Results: Among all patients with stage IV or recurrent, metastatic KRAS G12C mutant NSCLC (n = 201 with KRAS G12C confirmed prior to first line systemic therapy), the median first-line rwPFS was 9.3 months (95% CI, 7.3-11.8 months) and median OS was 16.8 months (95% CI, 12.7-22.3 months). In this historical dataset, first line systemic therapy among these 201 patients included platinum doublet alone (44%), PD-(L)1 inhibitor monotherapy (30%), platinum doublet chemotherapy plus PD-(L)1 inhibitor (18%), and other regimens (8%). Among patients with documented second-line systemic therapy (n = 123), the second-line median rwPFS was 8.3 months (95% CI, 6.1-11.9 months), with median rwPFS 4.6 months (95% CI, 1.4-NA) among 10 docetaxel-treated patients (9 received docetaxel and 1 received docetaxel plus ramucirumab). Within the total study population, 49 patients (12%) had a co-occurring STK11 mutation and 3 (1%) had a co-occurring KEAP1 mutation. Among the 49 patients with a co-occurring KRAS G12C and STK11 mutation, median rwPFS on first-line systemic therapy (n = 23) was 6.0 months (95% CI, 4.7-NA), and median OS was 14.0 months (95% CI, 10.8-35.3 months). Conclusion: In this large, multicenter retrospective chart review of patients with KRAS G12C mutant NSCLC we observed a relatively short median rwPFS of 4.6 months among 10 patients with KRAS G12C mutant NSCLC treated with docetaxel with or without ramucirumab in the second-line setting, which aligns with the recently reported CodeBreak 200 dataset.

Median stromal tumor-infiltrating lymphocytes

e16254 Background: Neo-adjuvant therapy (NAT) and associated pathologic complete response (pCR) rates have correlated with improved survival in resected pancreatic ductal adenocarcinoma (PDAC). In this study, we explored the relationship between pathologic response, peri-operative therapy, and survival, especially the impact of change in adjuvant therapy in patients with no/poor path response to NAT. Methods: Retrospectively reviewed 66 PDAC patients who received NAT ± radiation and underwent resection at KU Cancer Center between 2011-2022. We compared DFS and OS between Path Responders vs Non-Responders based on standard Tumor Regression Scores from pathology reports. A subanalysis was performed in path non-responders based on switch in adjuvant therapy (AT) versus not. Results: Patient characteristics are summarized in the table. Among 66 PDAC patients, 50 (75.8%) achieved a path response (G0-G2), 16 (24.2%) experienced no/poor path response (G3). Of the 50 pts who achieved a path response, 4 (8.0%) had a complete path response (pCR; G0), 5 (10%) marked response (G1), 41 (82%) moderate response (G2). Median DFS (mDFS) was 17.3 months (95% CI: 12.7-22.4) in Path Responders vs 15.9m (95% CI: 9.6-35.8) in Non-Responders [p=0.59]. Median OS (mOS) was 32.9m (95% CI: 23.4-41.5) vs 27.7m (95% CI: 15.2-38.2), respectively [p=0.39). A sub-analysis in the Non-Responders (n=16) based on switch in AT (n=8) vs not (n=3), revealed mDFS 16.4m (95% CI: 9.6-41.8) when AT was switched vs mDFS 11.3m (95% CI: 5.9-16.6) when AT was not switched [p=0.24]; and mOS 30.6m (95% CI: 15.7-60.3) vs 17.2 months (95% CI: 6.7-27.7), respectively [p=0.18]. Conclusions: Our study found no statistical difference in DFS and OS between Pathologic Responders and Non-Responders to neo-adjuvant therapy. However, a sub-analysis within Pathologic Non-Responders revealed a longer DFS and OS after switching adjuvant therapy without reaching statistical significance, likely due to small sample size. Our findings warrant validation in a larger cohort as switch in adjuvant therapy could potentially change the treatment landscape for Pathologic Non-Responders.[Table: see text]

Abstract BACKGROUND H3 K27M-mutant DMG predominantly affects children and young adults; no effective therapy is known. ONC201 is a first-in-class, anti-cancer DRD2 antagonist and ClpP agonist. METHODS Fifty pediatric and adult patients with recurrent H3 K27M DMG who received oral ONC201 monotherapy in clinical trials and expanded access were selected for a planned efficacy analysis. Eligibility criteria included measurable contrast-enhancing disease by RANO-HGG criteria (excluding pontine and spinal cord tumors), KPS/LPS≥60, ≥90 days from prior radiation, and adequate washout from prior anti-cancer therapy. The primary endpoint was overall response rate (ORR) by RANO-HGG criteria. Secondary endpoints included duration of response, time to response, progression-free survival (PFS), overall survival (OS), corticosteroid response rate, performance status response rate, and ORR by RANO-LGG criteria. Radiographic endpoints were assessed by dual-reader blinded independent central review. Data cutoff was May 31, 2021. RESULTS ORR was 20.0% (95%CI, 10.0–33.7) by RANO-HGG criteria. Median duration of response was 11.2 months (95%CI, 3.8–not reached) and median time to response was 8.3 months (range, 1.9–15.9). PFS at 6 months was 35.1% (95%CI, 21.2–49.3). The ORR was 26.0% (95%CI, 14.6–40.3) by RANO-LGG criteria. Fifteen patients (30.0%; 95%CI, 17.9–44.6) achieved an objective response by RANO-HGG and/or RANO-LGG criteria. Of 15 patients receiving ≥4 mg daily dexamethasone at baseline, 7 (46.7%; 95%CI, 21.3–73.4) achieved ≥50% confirmed reduction in dose. Of 34 patients with baseline KPS/LPS <80, 7 (20.6%; 95%CI, 8.7–37.9) achieved a confirmed performance status improvement. With a median follow-up of 18.8 months, median OS was 13.7 months (95%CI, 8.0–20.3) and OS at 24 months was 34.7% (95%CI, 20.7–49.2). Twenty-five patients had serious adverse events with one possibly related to ONC201 by investigator assessment. CONCLUSIONS ONC201 monotherapy exhibits durable and clinically meaningful efficacy in recurrent H3 K27M-mutant DMG.

Aim:177Lu-Dotatate (Lu-177), a form of peptide receptor radionuclide therapy (PRRT), was approved by Food and Drug Administration (FDA) for the treatment of somatostatin-receptor-positive neuroendocrine tumors (NETs) in 2018. Clinical trials prior to the FDA approval of Lu-177 showed favorable outcomes but there is limited published real world outcomes data. This study aims to describe and analyze real world outcomes of patients with NET who received Lu-177.Methods:After obtaining institutional review board approval, retrospective evaluation was performed to analyze the efficacy of Lu-177 for somatostatin receptor-positive gastro-entero-pancreatic NETs (GEP-NETs) patients at the University of Kansas Cancer Center between June 2018 and September 2021. This study aims to determine the response rate to the treatment of the entire cohort and subgroups.Results:A total of 65 patients received Lu-177 of which 58 completed treatment. The 58 patients had a median age of 61.5 years, 24 females and 34 males, 86% Caucasian and 12% black. The origins of NETs were primarily small bowel (n = 24) and pancreatic (n = 14). Pathology showed grades 1 (n = 21), 2 (n = 25), and 3 (n = 4) and were primarily well-differentiated tumors (n = 4). Among the cohort, 52 patients had imaging to assess response with 14 (26.9%) patients with partial response (PR), 31 (59.6%) with stable disease (SD), and 7 (13.5%) with progressive disease (PD). In a subset analysis, patients with non-functional disease (n = 29) had higher rates of PR 42.3% (compared to 11.5%, P = 0.0147) and higher disease control rate of 96% (compared to 78%, P = 0.042) than patients with functional disease (n = 29). Patients with non-functional disease had a lower PD of 3.85% (compared to 23%, P = 0.0147) than those with functional disease.Conclusions:This real world outcomes analysis of NETs treated with Lu-177 shows improved PR when compared to the initial clinical trials and is promising for patients. In addition, patients with non-functional tumors were found to have a statistically significant improved response rate which has not been described in the literature before. If these study findings are validated in a larger cohort they may guide patient selection for Lu-177 therapy in the future.

Background: Previous trials have shown improved efficacy of neoadjuvant treatment when combined with angiotensin II receptor antagonist, losartan in patients with locally advanced pancreatic ductal adenocarcinoma (PDA). However, role of losartan is unknown in metastatic PDA. In this retrospective observational study, we examined the relationship between losartan use at time of diagnosis and continued through chemotherapy treatment with clinical outcomes in patients with metastatic PDA that received chemotherapy. Methods: We retrospectively evaluated 114 metastatic PDA patients treated at University of Kansas Cancer Center between January 2000 and November 2019. We compared overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) between patients using losartan at time of their cancer diagnosis and a control group of patients who were not on losartan. A subgroup analysis was performed based on patients who were on a 100 mg dose of losartan along with chemotherapy versus patients treated with chemotherapy (without losartan). Another subgroup analysis was performed based on chemotherapy regimen: Fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) versus Gemcitabine and Abraxane. Results: No significant difference was found in OS (p=0.466) or PFS (p=0.919) in patients on losartan (median 274 day, 83 day) and control patients (median 279 day, 111 day). No significant difference was found in ORR (p=0.621) or in DCR (p=0.497). No significant difference was found in OS (p=0.771) or PFS (p=0.0604) in losartan patients (median 347 day, 350 day) and control patients (median 333 day, 101 day) treated with FOLFIRINOX. No significant difference was found in OS (p=0.916) or PFS (p=0.341) in losartan (median 312 day, 69 day) and control patients (median 221 day, 136 day) treated with Gemcitabine plus Abraxane. No significant difference was found in OS (p=0.727) or PFS (p=0.790) in 100 mg losartan patients (median 261 day, 84 day) and control (median 279 day, 111 day). Conclusions: Patients on losartan at time of diagnosis and continued through chemotherapy treatment had no significant difference in OS, PFS, ORR, DCR than control patients. Subgroup analysis of patients treated with FOLFIRINOX revealed a longer PFS with losartan than control but did not reach statistical significance, likely due to small sample size. Our findings should be validated in a larger cohort to confirm if the benefit of losartan and FOLFIRINOX seen in a neoadjuvant setting for locally advanced cancer also applies to metastatic cancer. Relevance for Patients: This research adds to growing data on the efficacy of angiotensin receptor blocking drugs as adjunctive treatment in addition to chemotherapy in pancreatic cancer with specific focus on metastatic disease.

e18578 Background: Obesity is a bona fide risk factor for ICU admission, mechanical ventilation, and mortality in patients (pts) with COVID-19 in the general population. However, whether obesity is a risk factor in cancer pts remains unknown. Herein, we have conducted a systematic review/meta-analysis of obesity and all-cause mortality in cancer pts with COVID-19. Methods: Following PRISMA guidelines,a systematic search of PubMed and Embase as well as major conference proceedings (ASCO/ESMO/AACR) was conducted for publications from inception to 14 January 2020. Observational studies that reported all-cause mortality in cancer pts with lab confirmation or clinical diagnosis of COVID-19 and BMI (obese (>30 kg/m 2 ) vs. non-obese) were included in the analysis. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated with the fixed-effects model based on low heterogeneity. Small sample publication bias was evaluated using the Begg’s Funnel Plot and Egger’s test. Results: After reviewing 3387 studies,3 retrospective cohort studies of 419 obese and 1694 non-obese cancer pts (N=2117) with COVID-19 in both inpatient/outpatient settings that reported outcomes based on obesity were found. The 3 studies were conducted multi-nationally in North America, in France, and in the Netherlands respectively. The median ages of the cohorts ranged 66-68. All studies included various cancers of various stages and were of high quality per Newcastle Ottawa scale (scores 7-9). Fixed effects meta-analysis showed no association between obesity and all-cause mortality (OR 0.95, 95% CI 0.74-1.23) in cancer pts with COVID-19. Heterogeneity was low (I 2 = 33%). No significant funnel plot asymmetry was detected per Egger’s test (P=0.2273). The reported OR of each study is outlined in the table. Conclusions: In contrast to the general population, our analysis reveals that obesity is not associated with increased all-cause mortality in cancer pts with COVID-19. Limitations of this study include a limited number of included studies, reliance on retrospective studies, non-use of ethnicity-specific WHO BMI criteria, and limited granularity of the study-reported BMI. Future prospective studies are warranted to assess the complex interplay among anthropomorphic measures, cachexia/sarcopenia, comorbidities associated with the metabolic syndrome, and COVID-19 outcomes in the cancer pt population.[Table: see text]

6556 Background: CAR T-cell therapy is a type of adoptive cell transfer (ACT). In 2017 CAR T-cell therapy was approved by the Food and Drug Administration (FDA) for management of diffuse large B-cell lymphoma refractory to at least two prior lines of therapy (DLBCL) including primary mediastinal large B-cell lymphoma (PMBCL), and B cell precursor acute lymphoblastic leukemia (ALL) up to 25 years of age that is refractory or in second or later relapse. Since its inception, several patients underwent CAR T-cell therapy but data on real world outcome is limited. In this study we aim to evaluate the in-hospital outcomes of CAR T-cell therapy in the United States in 2018. Methods: This is a cross-sectional study using National Inpatient Sample 2018 database. Discharges with the ICD-10-PCS code for CAR T-cell therapy and ICD-10-CM code of ALL, DLBCL or PMBCL were included in the study. We analyzed their in-hospital outcomes (Total discharges, length of stay in days, hospitalization cost, and mortality - number of deaths). We applied the cost to charge ratio to hospitalization charges to estimate the mean hospitalization cost. The weighted sample represents national estimates. Results: We identified 785 discharges with CAR T cell therapy and diagnosis of ALL, DLBCL or PMBCL. 155 (19.75 %) were ALL, 620 (78.98%) DLBCL, and 10 (1.27%) PMBCL. Mean length of stay for the study cohort was 23.26 days. Specifically, for ALL mean LOS was 33.67 days, DLBCL 20.76 days, and PMBCL 17 days. Mean hospitalization cost for the study cohort was $285,989, specifically for ALL it was $342,228, DLBCL $274,102, PMBCL $179,431. There were a total of 60 (7.6%) deaths in the study cohort. Diagnosis specific mortality was 20 (12.9%) in ALL, 40 (6.4%) in DLBCL and none in PMBCL. Conclusions: Majority of discharges who underwent CAR T-cell therapy were DLBCL followed by ALL and PMBCL. CAR-T Cell hospitalizations have high costs and long length of stays. Mean length of stay was highest in ALL discharges, least in PMBCL. Mean hospitalization cost was higher in DLBCL discharges compared to ALL and was least in PMBCL discharges. The in-hospital mortality with the CAR-T cell therapy appears to be higher than reported in clinical trials, especially for ALL. [Table: see text]

Abstract Purpose: Addition of carboplatin (Cb) to anthracycline chemotherapy improves pathologic complete response (pCR), and carboplatin plus taxane regimens also yield encouraging pCR rates in triple-negative breast cancer (TNBC). Aim of the NeoSTOP multisite randomized phase II trial was to assess efficacy of anthracycline-free and anthracycline-containing neoadjuvant carboplatin regimens. Patients and Methods: Patients aged ≥18 years with stage I–III TNBC were randomized (1:1) to receive either paclitaxel (P) weekly × 12 plus carboplatin AUC6 every 21 days × 4 followed by doxorubicin/cyclophosphamide (AC) every 14 days × 4 (CbP → AC, arm A), or carboplatin AUC6 + docetaxel (D) every 21 days × 6 (CbD, arm B). Stromal tumor-infiltrating lymphocytes (sTIL) were assessed. Primary endpoint was pCR in breast and axilla. Other endpoints included residual cancer burden (RCB), toxicity, cost, and event-free (EFS) and overall survival (OS). Results: One hundred patients were randomized; arm A (n = 48) or arm B (n = 52). pCR was 54% [95% confidence interval (CI), 40%–69%] in arm A and 54% (95% CI, 40%–68%) in arm B. RCB 0+I rate was 67% in both arms. Median sTIL density was numerically higher in those with pCR compared with those with residual disease (20% vs. 5%; P = 0.25). At median follow-up of 38 months, EFS and OS were similar in the two arms. Grade 3/4 adverse events were more common in arm A compared with arm B, with the most notable differences in neutropenia (60% vs. 8%; P < 0.001) and febrile neutropenia (19% vs. 0%; P < 0.001). There was one treatment-related death (arm A) due to acute leukemia. Mean treatment cost was lower for arm B compared with arm A (P = 0.02). Conclusions: The two-drug CbD regimen yielded pCR, RCB 0+I, and survival rates similar to the four-drug regimen of CbP → AC, but with a more favorable toxicity profile and lower treatment-associated cost.

The incidence of lung cancer has been declining in the United States (US) from 2007 to 2014. However, the impact of the implementation of low dose CT screening (LDCT) in high-risk population in 2015, on the incidence of lung cancer and on the proportion of patients with metastatic disease at the time of diagnosis in that population is unknown. We conducted a cross-sectional study using Surveillance, Epidemiology, and End Results data to identify trends of incidence of lung cancer and the proportion of patients with metastatic disease at the time of diagnoses across 4 periods from 2007 to 2016. Period 1 and period 2 occurred before the publication of the National Lung Cancer Screening Trial (NLST) to establish baseline trends (2007- 2009 and 2010- 2011 respectively). Period 3 and period 4 were after the publication of NLST (2012-2014) and LDCT implementation (2015-2016) respectively. The population of interest was between the age of 55-79 years. The study included 471,300 patients with newly diagnosed lung cancer with age of 55-79 years (mean age 68.2 [6.7] years, 52.5% male, 83.3% white, 11.1% black and 5.4% Hispanic). The age-adjusted incidence of lung cancer steadily declined from 243.9 per 100k population in period 1 to 203.2 per 100k population in period 4. The proportion of patients with metastatic disease at the time of diagnoses was stable before the publication of NLST (0.04% increase from period 1 to period 2, p=0.8) and remained stable after the publication of NLST until the implementation of LDCT (0.28% decrease from period 2 to period 3, p=0.2). Compared with this baseline trend, implementation of LDCT was significantly associated with a decrease in the proportion of patients with metastatic disease at the time of diagnoses (3.29% decrease from period 3 to period 4: difference in change, -3.33%, P < 0.01). These results were consistent in sex (male or female) and ethnic (Hispanic or non-Hispanic) subgroups. After the implementation of LDCT screening, the proportion of lung cancer patients with metastatic disease at the time of diagnosis has declined in the US without any impact on trends of incidence of lung cancer among the population with age of 55-79 years.

The impact of the implementation of low dose CT screening (LDCT) in high-risk population in 2015, on the proportion of patients with metastatic disease at the time of diagnosis of Lung cancer in different racial subgroups is unknown. The racial difference in the proportion of population eligible for LDCT is also unknown. We conducted a cross-sectional study using SEER data to identify trends of the proportion of patients with metastatic disease at the time of diagnoses across 4 periods from 2007 to 2016. Period 1 (P1) and period 2 (P2) occurred before the publication of the National Lung Cancer Screening Trial (NLST) to establish baseline trends (2007-2009 and 2010- 2011 respectively). Period 3 (P3) and period 4 (P4) were after the publication of NLST (2012-2014) and LDCT implementation (2015-2016) respectively. We also analyzed the National Health and Nutrition Examination Survey (NHANES) to estimate the proportion of population meeting the LDCT criteria from 2015 to 2016. The population of interest was between the age of 55-79 years. The study included 471,300 patients with newly diagnosed Lung cancer with age of 55-79 years (mean age 68 years, 53% male, 83% white, and 11% African Americans [AA]). Among whites, the proportion of patients with metastatic disease at the time of diagnoses was stable before the publication of NLST (0.1% decline from P1 to P2, p = 0.7) and remained stable after the publication of NLST until the implementation of LDCT (0.3% decline from P2 to P3, p = 0.2). Compared with this baseline trend, implementation of LDCT was significantly associated with a decline in proportion of patients with metastatic disease at the time of diagnoses (3.6% decline from P3 to P4: difference in change, -3.5%, p < 0.01). In AA, compared to the baseline trend, implementation of LDCT was associated with a declining trend in the proportion of patients with metastatic disease at the time of diagnoses (2.1% decline from P3 to P4: difference in change, -1.7%, p = 0.06). However, the magnitude of decline was smaller and not statistically significant in AA compared to whites. From 2015 to 2016, the estimated proportion of the population with age of 55-79 years eligible for LDCT was significantly lower in AA compared to whites (2.1% vs 7.1%, p < 0.01). After the implementation of LDCT in 2015, the proportion of Lung cancer patients with metastatic disease at the time of diagnoses has declined in the US among whites but not yet in AA with age of 55-79 years. Further research is needed to identify if the observed racial difference is due to the underutilization of LDCT in AA.