Higher Median Overall Survival Research Articles

Racial disparities in the attainment of textbook oncologic outcomes following colectomy for colon cancer: a national cancer database cohort study.

Textbook oncologic outcome (TOO) is attained when all desired short-term quality metrics are met following an oncologic operation. The objective of this study was to determine the impact of race on TOO attainment following colectomy for colon cancer. The 2004-2017 National Cancer Database was queried for patients with non-metastatic colon cancer who underwent colectomy. TOO was defined as: negative margins (R0), adequate lymphadenectomy (LAD) (n ≥ 12), no prolonged length of stay (LOS), no 30-day readmission or mortality, and initiation of systemic therapy in ≤ 12weeks. Racial groups were defined as White, Black, or Hispanic. 508,312 patients were identified of which 34% achieved TOO. Blacks attained the least TOO (31.4%) as well as the TOO criteria of adequate LAD (81.1%), no prolonged LOS (52.3%), and no 30-day readmission (89.7%). Hispanics were least likely to have met the criteria of R0 resection (94.3%), no 30-day mortality (87.3%), and initiation of systemic therapy in ≤ 12weeks (81.8%). Patients who attained TOO had a higher median overall survival (OS) than those without TOO (148.2 vs. 84.2months; P < 0.001). Hispanic TOO patients had the highest median OS (181.2months), while White non-TOO patients experienced the lowest (80.2months, P < 0.001). Multivariate logistic regression models suggest that Black and Hispanic patients are less likely to achieve TOO than their White counterparts. Racial disparities exist in the achievement of TOO, with Blacks and Hispanics being less likely to attain TOO compared to their White counterparts.

Abstract 3821: Real world outcomes among patients with newly diagnosed acute myeloid leukemia

Abstract Introduction: Treatment options for patients with acute myeloid leukemia (AML) have expanded in recent years. Although new treatments have demonstrated efficacy in clinical trials, less is known about their effect on outcomes in routine clinical practice. We examined outcomes for patients with newly-diagnosed AML (ND-AML) using real world data (RWD). Methods: This retrospective observational study was conducted using the COTA real-world (rw) database, a de-identified source of longitudinal electronic health record data pertaining to the diagnosis, management, and outcomes of patients with cancer. Adult patients with ND-AML, diagnosed January 1, 2013 to March 20, 2023 were included. First-line treatment regimens were grouped into therapeutic categories and outcomes were summarized. The index date was defined as date of initiation of first-line therapy. Results: Among 2516 patients with ND-AML included (Table), the most common regimens used were intensive chemotherapy with cytarabine (IC w/ara-C), hypomethylating agents with venetoclax (HMA+ven), and HMA alone. Complete response rate was highest in patients treated with IC w/ara-C or investigational regimen(s). Median overall survival (OS) was 16 mo overall, with highest median OS seen in patients treated with IC w/ara-C and investigational regimen(s). Median OS for patients treated with HMA+ven was 13.5 mo. Thirty-day mortality was lowest in patients treated with IC w/ara-C, CPX-351 (liposomal daunorubicin + cytarabine), and HMA+ven. Conclusions: Results suggest that IC w/ara-C remains the standard of care for most patients with ND-AML and this regimen has a higher CR rate and median OS. Variation of patient demographics and clinical characteristics across treatment groups did not permit cross-treatment comparisons, though future analyses evaluating these subgroups may provide further insight into effectiveness and safety of AML regimens in routine care for populations underrepresented in clinical trials. rwCR rate Median rwOS 30-day mortality N % (95% CI) Months (95% CI) % (95% CI) Overall 2516 45.3 (43.2, 47.3) 16.0 (14.9, 17.3) 5.9 (5.0, 6.8) IC w/ara-C 1171 60.6 (57.8, 63.4) 36.4 (31.0, 46.0) 1.6 (0.9, 2.3) HMA+ ven 300 33.7 (28.3, 39.3) 13.5 (11.4, 15.5) 3 (1.1, 4.9) Decitabine 242 12.8 (8.9, 17.7) 8.4 (6.7, 9.9) 10.4 (6.5, 14.2) Azacitidine 206 7.8 (4.5, 12.3) 7.2 (5.3, 9.6) 10.7 (6.4, 14.8) Investigational 206 61.6 (54.6, 68.3) 21.3 (15.2, 27.8) 3.4 (0.9, 5.9) Lower dose cytarabine 62 12.9 (5.7, 23.9) 8.7 (5.4, 16.1) 14.9 (5.4, 23.4) CPX-351 based 61 55.7 (42.4, 68.5) 9.3 (7.3, 15.1) 0.0 No treatment 188 NA 1.9 (1.5, 2.8) 30 (22.7, 36.6) Citation Format: Elizabeth D. Pulte, Laura L. Fernandes, Joseph Wynne, Eric Hansen, Andrew J. Belli, Anna Barcellos, Christina M. Zettler, Rebecca Bystrom, Jonathon Vallejo, Wenjuan Gu, Catherine Lerro, Kelly Norsworthy, Angelo DeClaro, Marc R. Theoret, Donna Rivera, Ching-Kun Wang. Real world outcomes among patients with newly diagnosed acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3821.

Comparative study on the efficacy and safety of transarterial chemoembolization combined with hepatic arterial infusion chemotherapy for large unresectable hepatocellular carcinoma.

Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) are two new treatments for hepatocellular carcinoma (HCC). Previous studies had reported that TACE combined with HAIC conferred better survival benefit than TACE alone. The study was to evaluate the availability and safety of TACE combined with HAIC for the treatment of large HCC. Patients with unresectable large HCC who underwent TACE combined with HAIC (TACE-HAIC group) and HAIC alone (HAIC group) at the Department of Interventional Radiology between August 2018 and September 2022 were retrospectively enrolled in this study. Overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) were used to evaluate the efficacy and safety of the two groups by using log-rank test. The independent factors of OS of large HCC patients were investigated by Cox regression model. A total of 73 patients (mean age, 59.8±8.8; 60 men) with unresectable large HCC were finally screened in the current study, including 32 who received TACE combined with HAIC and 41 who received HAIC alone. Compared with patients in HAIC group, TACE-HAIC group had higher median OS (37.1 vs. 14.9 months, P=0.0014). Similarly, PFS in the TACE-HAIC group was longer than that in the HAIC group (16.5 vs. 6.9 months, P=0.0037). The objective response rate (ORR) was 65.6% vs. 53.7% and the disease control rate (DCR) was 90.6% vs. 78.0% in the two groups, neither was statistically significant (P=0.345 and 0.208, respectively). All AEs related to therapy were manageable, and there were no significant differences in the incidence of any grade and grade 3/4 AEs between the two groups (P>0.05). TACE combined with HAIC yielded a promising prognosis in treating patients with large HCC compared with HAIC alone, with tolerable toxicity.

Primary and Secondary Plasma Cell Leukemia Risk Stratification By Circulating Plasma Cells

Plasma cell leukemia (PCL) is a rare plasma cell dyscrasia associated with poor outcomes. PCL can present de novo as primary PCL (pPCL) or from preceding multiple myeloma as secondary PCL (sPCL). The International Myeloma Working Group (IMWG) in 2021 updated the diagnostic criteria for pPCL using circulating plasma cells (CPC) to ≥5% instead of ≥20% as both carry similar survival. In this single center retrospective analysis, we compared clinical features and overall survival (OS) for 104 patients: with pPCL ≥5% CPC ( N = 35), sPCL 5-19% CPC (sPCL-A) ( N = 11), sPCL ≥20% CPC (sPCL-B) ( N = 38), and spillover group 1-4% CPC regardless of newly diagnosed or secondary status ( N = 20). Mean ages were 57 - 59 years old for all groups (range: 25 - 84) with no difference in age between groups ( p = 0.90). There was a slight predominance of females (54.8%) over males and blacks (53.9%) over non-blacks. More patients with pPCL were black (65.7%) compared to sPCL and spillover groups, although this difference was not statistically significant ( p = 0.35). pPCL patients presented with the highest mean WBC at diagnosis (23.4 x10 9/L) compared to sPCL-A (5.5 x10 9/L), sPCL-B (12.2 x10 9/L), and spillover (7.2 x10 9/L) groups ( p &amp;lt;0.001). Patients in all groups were anemic (hemoglobin 7.8 - 9.3 g/dL), thrombocytopenic (platelets 60.2 - 101.2 x 10 9/L), and had abnormal renal function (creatinine 1.4 - 2.7 mg/dL), elevated LDH (918.7 - 1515.5 units/L, highest in sPCL-A), and elevated uric acid levels (5.9 - 8.2 mg/dL). sPCL patients and spillover group had more lytic lesions on skeletal survey ( p = 0.009) and positron emission tomography (PET) ( p = 0.02) compared to patients with pPCL. sPCL-A patients had higher incidences of lymphadenopathy ( N = 5/11, 62.5%, p = 0.02) and central nervous system invasion ( N = 4/11, 36.4%, p = 0.02) compared to other groups. There was no difference in incidence of extramedullary disease ( p = 0.29) between groups. Over 90% of patients with PCL had high-risk cytogenetics with 63% carrying a complex karyotype. Hypodiploidy was seen more often in patients with pPCL and sPCL-B compared to sPCL-A and spillover ( p = 0.005). There was no difference between groups in incidence of deletion 17p ( p = 0.53). All patients benefited in terms of OS from daratumumab (HR 0.44, 95% CI 0.25 - 0.76; p = 0.004), IMiDs (HR 0.13, 95% CI 0.08 - 0.23; p &amp;lt;0.001), PIs (HR 0.43, 95% CI 0.25 - 0.75; p = 0.003), chemotherapy (HR 0.56, 95% CI 0.32 - 0.98; p = 0.04), and autologous hematopoietic stem cell transplantation (HR 0.33, 95% CI 0.16 - 0.71; p = 0.004). DVT-PACE type regimens (dexamethasone-bortezomib-thalidomide-cisplatin-doxorubicin-cyclophosphamide-etoposide) are used for pPCL and may be less effective in sPCL and spillover patients who have been heavily pretreated. We noted no benefit in OS for all patients including pPCL, sPCL-A, sPCL-B, and spillover groups who received DVT-PACE (HR 0.97, 95% CI 0.62 - 1.50, p = 0.88). The lack of OS benefit in pPCL patients receiving DVT-PACE persisted on multivariate analysis when adjusting for PCL group alone (HR 0.79, 95% CI 0.50 -1.26; p = 0.33) and PCL group, age, platelet count, and presence of high-risk cytogenetics (HR 1.11, 95% CI 0.63 - 1.94; p = 0.72). After median follow-up of 6.70 months, median OS was 7.14 months for the entire cohort with 92.3% ( N = 96) deceased. On univariate analysis, male sex, age &amp;gt;58 years old, high-risk cytogenetics, LDH &amp;gt;604 units/L, creatinine &amp;gt;1.40 mg/dL, hemoglobin &amp;lt;8.3 g/dL, platelets &amp;lt;53.5 x10 9/L, lytic lesions on skeletal survey and on PET, extramedullary disease on PET, and plasmacytoma were associated with inferior median OS (Table 1). pPCL had higher median OS (13.1 months) compared to sPCL-A (3.1 months, p = 0.03) and sPCL-B (3.5 months, p = 0.003) (Figure 1). There was no statistically significant difference in median OS between pPCL (13.1 months) and spillover patients (10 months) ( p = 0.48) as well as sPCL-A (3.1 months) and sPCL-B (3.5 months) ( p = 0.80). Although the spillover group was associated with a trend towards better OS compared to sPCL-A and sPCL-B groups, this was not statistically significant, which may be due to low N which is a limitation of the study. Further research is required to better understand the clinical features, treatment responses, and outcomes of pPCL, sPCL, and spillover group (1-4% CPC).

Outcomes of Vdpace for Relapsed/Refractory Multiple Myeloma in the Era of Daratumumab Based Therapy

Background: Although the number of therapeutic options for patients with relapsed/refractory multiple myeloma (RRMM) has increased substantially, it still remains incurable and there remains a significant unmet need for treatment options for highly refractory patients. In this single-center real-world retrospective analysis, we evaluated the efficacy and safety of VDPACE (bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide) as a salvage therapy in the era of daratumumab. Methods: We retrospectively analyzed 88 patients with RRMM who received at least 1 cycle of VDPACE, between 1/2016 till 6/2023 at the University of Kansas Health System in collaboration with the U.S Myeloma Innovations Research Collaborative (USMIRC). VDPACE consists of Bortezomib 1 mg/m2 subcutaneous on days 1, 4, 8 and, 11, doxorubicin 10 mg/m2 continuous infusion (CI) x 4 days, cisplatin 10 mg/m2 CI x 4 days, cyclophosphamide 400 mg/m2 CI x 4 days and etoposide 40 mg/m2 CI x 4 days. In this patient population, we identified two groups - 28 patients who were naïve to daratumumab (DN) and 60 patients who were refractory to daratumumab (DR). Descriptive analysis was performed on available data for patient characteristics, disease course and outcomes differentiating these two groups. Adverse events were graded based on the CTCAE v5.0 criteria. Responses to therapy including overall response rate (ORR), complete response or better (≥CR), and very good partial response (VGPR) were evaluated using the International Myeloma Working Group (IMWG) criteria. The Kaplan-Meier method was used for progression free survival (PFS) and overall survival (OS) assessment. Results: The median age for the entire patient population was 63 years (41-77). Median lines of therapies (LOT) in DN vs DR groups were 2 (1-10) vs 5 (1-10), respectively (Table 1). The ORR and ≥VGPR in DR vs DN was 53% vs 50% and 15% vs 29%, respectively. With a median follow-of 11.3 months (95% CI, 4.03-27), the median PFS for the entire patient population was 4 months (95% CI, 2.97-5.43) while the median OS was 11.1 months (95% CI, 6.97-14.9). However, the median OS for DN was 15.9 months (95% CI, 8.73-29.5) compared to 7.03 months ((95% CI, 6.27-13.57) p=0.06) for the DR group. See Figure 1. Treatment related toxicities were similar in both groups. The most common grade III/IV hematological toxicities were neutropenia (96% vs 93%, p=0.99), thrombocytopenia (93% vs 80% p=0.2), lymphopenia (89% vs 95%, p=0.3), and anemia (79% vs 73%, p=0.79). Transfusion of packed red blood cells (64% in DN vs 68% in DR group) and platelet (61% vs 80%) were common in both groups. Rates of neutropenic fever were similar in both groups; 46% in the DN vs 35% in the DR group, p=0.62, with pneumonia being the most common infection seen in 11% vs 5% of the patients, respectively. Sixty-day Rehospitalization rates in the two groups were 21% vs 50%. There was no treatment-related mortality reported with this regimen. The difference in OS after VD-PACE in DR and DN patients could be explained by higher no of prior LOT, presence of high risk cytogenetics, double refractory status, and limited options available for salvage. Conclusions: Our study shows that while the response rates with VDPACE were comparable in the two groups, there was a higher median OS in the DN. Hematologic adverse events were common in both groups, but the rate of re-hospitalization was higher in the DR group. Based on these results, VDPACE remains a safe and effective salvage therapy for patients with RRMM. For DR patients receiving VD-PACE, strong consideration should be given to clinical trials given poor long-term outcomes.

Clinical and Molecular Characteristics of NPM1MTDe Novo AML ( NPM1MT dnAML) Differ from NPM1MT therapy-associated AML ( NPM1MT tAML)

Background: NPM1-mutated AML accounts for 30% of all adult AML cases and frequently carries a favorable prognostic impact when enriched by a normal karyotype and the absence of FLT3-ITD mutations. Although the clinical and molecular characteristics of NPM1-mutated de novo AML ( NPM1MT dnAML) are well known, the impact of NPM1MT within the context of therapy-associated AML ( NPM1MT tAML) remains controversial. Recent work by Othman et al. suggests NPM1MT tAML may represent a biologically de novo leukemia, displaying similar clinical, genomic, and transcriptional profile to NPM1MT dnAML and should be treated as a single disease entity. We sought to externally validate this by analyzing the clinical outcomes, mutational landscape, and molecular features of a large cohort of patients with NPM1-mutated AML. Methods: We conducted a large retrospective analysis of adult AML patients with NPM1MT by screening public databases, cBioPortal (Cerami et al., 2012) and AACR GENIE (v 13.1), and expanded with a published metanalytic cohort of various sub-studies from Cleveland Clinic Foundation from 2012-2021 (Awada et al., Blood 2021 and Kewan et al., Nature Communications, 2023). Baseline clinical and molecular characteristics were noted. We analyzed the molecular data in the context of overall survival (OS), clinical parameters, coexisting mutations, karyotype, AML subtypes, ELN-favorability, and gene expression data. Results: We screened a total of 15,742 adult AML patients, and 4,135 eligible patients were separated into 5 cohorts: 2,156 patients (52%) with NPM1MT dnAML, 1233 patients (30%) with NPM1WT sAML, 289 patients (7%) with NPM1MT sAML, 397 patients (10%) with NPM1WT tAML, and 60 patients (1.5%) with NPM1MT tAML. NPM1MT dnAML and NPM1MT sAML patients had a median age of 60 and 72 yrs. [18-91 vs 27-91 yrs., p =&amp;lt;0.0001 resp.]. NPM1MT tAML also had a median age of 72 yrs. [range 24-84]. Females were more represented in NPM1MT dnAML compared to both sAML cohorts [51% vs 45% and 39%; p =&amp;lt;0.0001, &amp;lt;0.0001] and both tAML cohorts. Abnormal karyotype enriched NPM1WT tAML more than NPM1MT dnAML [72% vs 27%, p =&amp;lt;0.0001], whereas normal karyotype was more prominent in NPM1MT dnAML compared to NPM1WT sAML, NPM1MT sAML, and NPM1WT tAML cohorts [72% vs 55%, 58% and 59%; p =&amp;lt;0.001, &amp;lt;0.001 and 0.0243 resp.]. FLT3-ITDNEG status dominated all 5 cohorts, NPM1 MT dnAML and NPM1WT t-AML had similar FLT3-ITDNEG mutants [83% vs 86%, p =0.52], and NPM1MT sAML had the highest FLT3-ITDPOS hits (32%). NPM1WT sAML cohort was profoundly hyperproliferative in bone marrow blast response (33.5%) whereas NPM1MT dnAML and NPM1MT tAML had similar responses (73% and 73%, p =0.3). All five cohorts were pancytopenic, the degree of pancytopenia was comparable in NPM1MT dnAML vs NPM1MT t-AML as shown below in Fig 1-A. NPM1 MT dnAML (Fig.1-B) had the best survival vs NPM1MT tAML [24.74 vs15.9 mo., p =&amp;lt;0.0016]. NPM1MT s-AML had the worst survival across all the cohorts, although comparable to NPM1WT tAML [8.73 and 9.76 mo., p =&amp;lt;0.0001]. When we exclude FLT-ITD, NPM1MT dnAML has the highest median OS, and median OS for NPM1MT t-AML rises as well [25 vs 23mo., p =0.0196], the remaining three cohorts had comparable OS (10.97 vs 10.63 vs 11.05 mo.). Next, we narrowed down to only ELN-favorable risk groups, median OS was only numerically higher for NPM1MT dnAML vs NPM1MT tAML [25 vs 23 mo., p-value =0.1348]. In terms of co-mutational profile, NPM1MT dnAML and NPM1MT tAML share many similarities though not with associated mutations: NPM1MT tAML is enriched by TP53 (10%), and SF3B1 (5%), and NPM1MT dnAML by RAD21 (5%) and CEBPA (5%) To understand gene-expression differences, we analyzed publicly available RNA-seq data for dn NPM1MT AML vs NPM1MT tAML and discovered that NPM1MT dnAML had higher expression of cMYC as well as FOXO1. Conclusion: Although dn NPM1MT AML and NPM1MT tAML appear to have distinct molecular and clinical profiles, a narrow focus on ELN-favorable patients demonstrates that both entities have similar clinicogenomic outcomes. When evaluated in a large cohort of AML patientswith added granularity from sAML cohorts, we notice several differences in survival and molecular profile that converge as more unfavorable factors, such as abnormal cytogenetics and FLT3-ITDPOS status are removed. Ongoing work at Karmanos Cancer Center is focused on evaluating differences in treatment response and gene-expression analysis based on RNA-seq.

Development and evaluation of 5FUCore, OxaliCore, and IrinoCore transcriptomic signatures for predicting response to individual drugs in the FOLFIRINOX regimen: Towards toxicity reduction and personalized chemotherapy in PDAC.

4141 Background: Recently, we have successfully developed a transcriptomic signature that predicts the response to gemcitabine treatment in patients with localized pancreatic ductal adenocarcinoma (PDAC) (PMID: 36178036) and also in those with metastatic PDAC (PMID: 36496056). This was achieved by using an approach that combined several preclinical PDAC models. The FOLFIRINOX regimen (FFX) consisting of 5-Fluorouracil (5FU), Oxaliplatin, and Irinotecan is the more effective treatment option, but the high toxicity limits its use. In this study, we developed and analyzed three different transcriptomic signatures for the drugs composing FFX separately and evaluated their clinical utility. Methods: We combined the transcriptomic profile of 14 patients derived xenograft (PDX) and 31 patients derived cell cultures (PDC) with their corresponding chemotherapy response profiles. We developed predictive signatures for 5FU ( 5FUCore), Oxaliplatin ( OxaliCore), and Irinotecan ( IrinoCore), as previously reported for the GemCore signature (PMID: 36178036). They were then validated in three independent cohorts of patients: COMPASS (n = 94), Linehan (n = 28), and a new cohort of 87 advanced PDAC patients. Results: Three ICA components that reflect the chemotherapy response profiles for 5FU, oxaliplatin, and irinotecan were evaluated in the COMPASS cohort to determine their ability to identify sensitive patients in the FFX arm. Patients predicted as sensitive to each drug separately had a median overall survival (OS) of 77.6 (95% CI, 67.9-NR, P =0.02), 78.7 (95% CI, 57.6-NR, P= 0.002), and 70.4 (95% CI, 57.6-NR, P= 0.02) months for 5FU, oxaliplatin, and irinotecan, respectively. Notably, the model that integrated the group of sensitive patients to two or three drugs had the highest median OS in the COMPASS and Linehan cohorts with a HR of 0.25 (95% CI, 0.11-0.57; P &lt; 0.001) and 0.11 (95% CI, 0.02-0.70; P= 0.019), respectively. Importantly, they also show a better objective response than the other groups ( P= 0.009). In the advanced PDAC group, the signatures showed a strong ability to discriminate sensitive patients in the FFX arm with a median OS of 20.1 (95% CI, 2.3-NR, P= 0.006), 13.64 (95% CI, 9.57-NR, P= 0.003), and 15.87 (95% CI, 2.9-NR, P= 0.002) months for 5FU, oxaliplatin, and irinotecan, respectively. Finally, we evaluated the best combination of two drugs in the pooled group. Patients sensitive to both 5FU and oxaliplatin showed the best response with 60% of patients achieving partial response. Conclusions: The signatures developed provide a tool for predicting responsiveness to the individual therapeutic drugs of the FFX regimen. They may ultimately lead to the development of a personalized strategy for combined chemotherapy regimens, increasing efficacy and reducing toxicity in PDAC.

Patterns of weight change and overall survival (OS) during first-line pembrolizumab treatment in patients with non-small cell lung cancer (NSCLC).

e21094 Background: Cancer-associated cachexia and weight change from treatment-related side effects profoundly influence treatment outcomes for patients with NSCLC. Limited data are available to compare the association between weight change and OS for patients with NSCLC treated with pembrolizumab alone or combined with chemotherapy. Therefore, we evaluated the change in weight after the first cycle of pembrolizumab-based treatments and its association with OS in patients with metastatic NSCLC. Methods: This retrospective study included 306 patients with NSCLC treated with a first line pembrolizumab-based regimen at Ohio State University from 2018-2021. Baseline characteristics were collected within seven days before cycle one treatment. Percent of weight change (PWC) was calculated as (cycle two weight – baseline weight)/baseline weight x 100%. Severe weight loss was defined as ≥75th percentile (PWC ≤-3.5%). Kruskal Wallis test was used to compare the significance of median PWC between treatment groups. Cox proportional-hazards models were used to test associations with survival. Results: The median age was 64.0 (IQR 56.7-72.6) years. The median baseline BMI was 26.1 (IQR 22.4-30.7). There was no difference between the median PWCs of patients treated with pembrolizumab monotherapy (-1.2%, IQR -3.7-0.8%) vs. pembrolizumab with chemotherapy (-1.0%, IQR -3.4-0.6%), p = 0.587. The patients whose weight remained stable (PWC -1% to 1%, n = 87 (28.4%)) had the highest median OS at 45.6 months (95% CI 27.6 – not reached); while those with severe weight loss (PWC ≤-3.5%, n = 78 (25.5%)) and weight gain (PWC ≥1%, n = 65 (21.2%)) had significantly decreased survival with median OS 15.6 (95% CI 9.3-20.9) and 16.3 (95% CI 10.1-25.6) months respectively, overall model p-value &lt; 0.001. The PWC remained significantly associated with OS after adjusting for performance status, PD-L1, and treatment with p &lt; 0.001 (Table 1). Conclusions: For patients with metastatic NSCLC treated with first line pembrolizumab-based regimen, similar PWCs were seen between patients treated with pembrolizumab alone or combined with chemotherapy. Regardless of treatment, weight gain and severe weight loss after the first cycle of treatment were associated with reduced OS. Further in-depth analysis is warranted to investigate the potential causes of weight changes, especially for patients with positive PWC. [Table: see text]

Chemotherapy dose density and effect on prognosis for patients with resectable pancreas cancer: A secondary analysis of SWOG S1505.

4158 Background: Chemotherapy is an integral part of multimodality treatment for resectable pancreatic ductal adenocarcinoma (PDAC). Assessing the impact of chemotherapy dose reductions or missed cycles on survival is difficult as few trials prospectively address the prognostic value of this important metric. Methods: SWOG S1505 (NCT02562716) was a randomized, phase II study of perioperative (12 weeks neoadjuvant and 12 weeks adjuvant) chemotherapy with mFOLFIRINOX or gemcitabine/nab-paclitaxel for resectable PDAC. Dose density (DD) was defined as the estimated percent of chemotherapy dose received of the total planned per protocol. Thresholds were based on published analyses and balance in sample size across treatment arms. Cox regression analysis of overall survival (OS) according to DD was performed in patients alive at two landmark time points: after surgery (among those who completed surgery) and at 40 weeks (when protocol therapy was to be completed). Results: Of the 103 eligible patients enrolled, median age was 64 years, 81% underwent pancreaticoduodenectomy, 15% distal pancreatectomy, and 3% a total pancreatectomy. In the 73 patients who underwent surgery, median neoadjuvant chemotherapy DD was 89%. Patients with ≥ 85% DD had higher median OS from surgery (38.1 v. 17.2 months, p = 0.039) compared to patients with &lt; 85% DD. Of the 82 patients who survived to 40 weeks post randomization, 67 underwent surgery and 58 started adjuvant chemotherapy. The median DD for all perioperative chemotherapy was 67%; DD was significantly higher for neoadjuvant compared to adjuvant therapy (83% vs. 58%, p &lt; 0.001). In this cohort, DD ≥ 70% was associated with better median OS from 40 weeks post randomization (32.2 v. 14.0 months, p = 0.017). DD was not significantly associated with pathologic response, margin status, or lymph node negativity. There were no significant differences in DD between the mFOLFIRINOX and gemcitabine/nab-paclitaxel arms. Conclusions: This is the first study to identify a prognostic role for chemotherapy DD in patients undergoing perioperative chemotherapy for resectable PDAC. Patients who received ≥ 85% DD preoperatively and/or ≥70% DD perioperatively had significantly higher mOS than those receiving a smaller proportion of protocol therapy. With greater survival benefit in patients who received higher chemotherapy DD, and higher DD being likelier in preoperative vs. postoperative treatment, these data support use of neoadjuvant chemotherapy for resectable PDAC. Moreover, these findings suggest that DD should be considered in prospective studies for localized PDAC to optimize therapy to be received.

Gender disparities in metastatic RCC therapies and outcomes.

4565 Background: The incidence of metastatic renal cell carcinoma (mRCC) is rising globally in both males and females. Previous studies have shown that females with mRCC experience better overall survival (OS) when compared to males. In the era of immunotherapy (IM) as part of standard of care, gender-based outcome disparities are unclear. In this study, we identify gender-specific trends in treatment regimen and OS. Methods: The National Cancer Database (NCDB) was queried from 2004 to 2019 for a retrospective cohort analysis of mRCC patients. 51,596 males and 25,528 females were reviewed. The primary endpoints were OS and predictors of receipt of IM. Kaplan-Meier (KM) analysis was used to assess gender-based OS and compare OS in patients who received or did not receive CN or IM. Binomial logistic regression was performed to examine gender as a predictor of treatment received. Cox proportional hazards model assessed the impact of age, gender, sites of metastases, Charleson-Deyo comorbidity classification, insurance type, treatment facility, year of diagnosis, CN, and IM on OS. Results: In KM analyses, females had lower median OS compared to males (7.200 months vs 8.940 months, p&lt;0.001). Higher median OS was found in patients who received IM (21.3 vs 7.6 months; p&lt;0.001) and CN (22.1 vs 5.13 months; p&lt;0.001). Logistic regression demonstrated that females were less likely to receive IM after controlling for the variables listed above (OR 0.839 (95% CI: 0.787 - 0.894), p&lt;0.001). Cox regression demonstrated that when adjusting for clinicopathologic variables and treatment regimen, female gender independently conferred a statistically significant negative impact on OS (HR = 1.039 (95% CI: 1.015-1.063), p=0.001). Conclusions: While CN remains an efficacious treatment option, advances in IM have led to targeted therapies that improve OS in mRCC patients. We demonstrate that a gender-based discrepancy in mRCC survival persists. In contrast to previous literature, our analysis found worse OS as well as an underutilization of IM in female mRCC patients. Moreover, females with mRCC have increased mortality even when accounting for IM. Therefore, further investigation is needed to elucidate the causes of survival discrepancy in the modern era of mRCC treatment. [Table: see text]

Outcomes of curative treatment for head and neck squamous cell carcinoma in very elderly adults ≥80 years old.

Head and neck cancer treatment can be difficult and advancing age is associated with greater frailty. It is unclear if curative treatment for very elderly patients is beneficial. This study compared outcomes to curative treatment in patients ≥80 aged with HNSCC to patients aged 70-79. Retrospective study of 114 patients diagnosed with HNSCC. Overall survival (OS), Disease-Free Survival (DFS), and local-regional control (LRC) were compared and adjusted for confounders. Patients aged 70-79 had a higher median OS (35 months [95% CI, 19.58-50.42]) compared with patients aged ≥80 (19 months [11.72-26.28]; p=0.008) but similar DFS and LRC. KPS < 90 was the stand-alone independent prognostic factor for OS (HR=2.14 [1.05-4.38]). Very elderly HNSCC patients (aged ≥80) can have favorable outcomes with curative therapy and advanced chronological age alone should not prohibit patients from receiving treatment. Performance status may be a greater predictor of survival outcome than age alone. Level III.

Clinical outcomes in immunotherapy and chemotherapy in minority populations with non-small cell lung cancer (NSCLC).

e20508 Background: Lung cancer is the leading cause of cancer deaths for Hispanics (HIS). Similarly, non-Hispanic blacks (NHB) are often disproportionately represented among cancer deaths compared to other racial/ethnic groups with lung cancer being the second most common cancer in black men and women, as well as the leading cause of cancer death. Despite these statistics, HIS and NHB remain underrepresented in non-small cell lung cancer (NSCLC) research. The aim of this study was to determine if there was a difference in outcomes between HIS, NHB and NH Whites (NHW) who had NSCLC and were treated with surgery, immunotherapy or chemotherapy. Methods: We studied 645,221 observations from the 2004-2018 National Cancer Database (NCDB), categorized as HIS, NHB or NHW, who received surgery, immunotherapy or chemotherapy for NSCLC. Categorical variables were analyzed using Pearson’s chi-square test or Fisher’s exact test. Continuous variables were analyzed using ANOVA. Survival outcomes were assessed using a Cox regression model and Kaplan-Meier curves with log-rank tests. Results: Regardless of treatment types, HIS had the highest median overall survival (OS) compared to other groups (NHW: 14.7 months; NHB: 15.0 months; HIS: 16.4 months) (P &lt; 0.001). Regardless of the type of systematic therapy received (immunotherapy or chemotherapy), HIS had the highest median OS (P &lt; 0.001) with HIS in the immunotherapy cohort having the highest survival advantage of all other race/ethnicity and chemotherapy groups. Multivariate Cox regression model further support the survival advantage of HIS compared to NHW (HR = 0.86; P = 0.009). OS was also assessed between patients who received surgery and/or chemotherapy. Patients who received a combination of surgery and chemotherapy had the highest OS compared to patients who underwent surgery only or received chemotherapy only. Among the cohort who received both, HIS had the highest median OS (NHW: 55.2 months; NHB: 55.5 months; HIS: 61.5 months). The surgery only cohort had the next highest median OS of all treatment groups; however, the HIS ethnicity group was non-estimable due to the small sample size. Of all three treatment groups, the chemotherapy only cohort had the lowest median OS while HIS had the highest median OS (NHW: 11.8 months; NHB: 12.9 months; H: 13.5 months) (P &lt; 0.001). Conclusions: Results of our study suggest immunotherapy may offer an increased survival advantage for HIS and NHB compared to chemotherapy. For patients receiving chemotherapy, a combination of surgery and chemotherapy may offer a greater survival advantage for NSCLC patients. Hispanic ethnicity was associated with better survival regardless of the type of treatment received.

Survival outcomes of pulmonary metastasectomy in advanced melanoma patients: An inverse probability weighted analysis.

e21518 Background: Pulmonary metastasectomy (PM) is a commonly performed procedure for certain patients with lung metastasis. We aimed to estimate the effect of PM on the survival outcomes of advanced melanoma patients with lung metastasis. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) database for all adult patients with advanced melanoma (AYA site recode) with lung metastasis (Stage M1b according to AJCC 7th edition) who were diagnosed from 2010 to 2015. Patients with known liver, brain, or bone metastasis were excluded. Our primary outcomes were overall survival (OS) and cancer-specific survival (CSS) in months. We used Kaplan-Meier plots to compare survival outcomes between treatment groups. We adjusted for potential confounders including age, sex, marital status, primary tumor surgery, chemotherapy, and radiotherapy in a multivariate analysis. We carried out an inverse probability (IP)-weighted Cox regression in an attempt to eliminate the effect of nonrandomization when estimating the treatment effect of PM on OS and CSS. Results: We included 520 patients; 98 (18.8%) underwent PM and 422 (81.2%) did not. The sample median age was 71 (IQR: 61-80). T0 stage was prevalent in 179 (34.4%) and N0-1 in 302 (58.1%). Primary surgical resection was performed for 217 (41.7%) patients, 136 (26.2%) patients had undergone chemotherapy, and radiotherapy was administered in 64 (12.3%) patients. Patients who underwent PM had a higher median OS than patients who did not (43.0 months, 95% CI: 25.0-not reached vs. 13 months, 95% CI: 11-16). The median CSS in PM group patients was not reached (95% CI: 43.0-not reached), while it was 16 months (95% CI: 13-21) in non-PM patients. After multivariate adjustment, older age, being single, and not undergoing primary surgical resection, were all significant independent prognostic factors for worse OS and CSS. In contrast, sex and receipt of chemotherapy and/or radiotherapy did not affect either OS or CSS. PM group patients had a significant survival advantage than non-PM patients, in terms of OS and CSS (HR = 0.50, 95% CI: 0.37-0.67 and HR = 0.45, 95% CI: 0.32-0.63, respectively). On the IP-weighted Cox analysis, the survival benefits of PM were still significantly favorable for OS (IP-weighted HR = 0.42, 95% CI: 0.30-0.59) and CSS (IP-weighted HR = 0.38, 95% CI: 0.26-0.57). Conclusions: PM in a multimodality treatment setting resulted in a marked survival advantage for patients with advanced melanoma who had lung metastasis only. The management of such patients should be delicately individualized to optimize their survival outcomes.

Prognostic impact of bone metastasis in patients with metastatic urothelial carcinoma (mUC) treated with durvalumab (D) with or without tremelimumab (T) in the DANUBE study.

4564 Background: In mUC, bone metastases (BM) are associated with significant morbidity and mortality, but their independent impact on outcomes is not well established, especially in the current era of immune checkpoint inhibitors (ICIs). This post-hoc analysis assessed the impact of BM, as well as PD-L1 status (within the same BM category) on outcomes of patients with mUC treated with ICIs. Data was derived from the Phase 3 DANUBE study, which compared D, D+T, and standard chemotherapy (SoC). Methods: Patient characteristics, disease characteristics, treatments, and outcomes were collected. Patients were categorized as having BM or no BM. Outcomes included median overall survival (OS) and median progression-free survival (PFS) (in months [mo]), estimated by the Kaplan-Meier method. PD-L1 expression was assessed using the VENTANA PD-L1 (SP263) Assay. Results: Overall, 1032 patients were included; 266 had BM (D, 80; D+T, 97; SoC, 89), and 766 had no BM (D, 262; D+T, 249; SoC, 255). Among all patients, those with BM had a lower OS than those with no BM (HR, 1.67; 95% CI, 1.43-1.92; nominal P&lt; 0.0001) when controlling for cisplatin eligibility, PD-L1 expression, presence of visceral metastases, and treatment. Similarly, patients with BM had lower PFS compared to those without BM (HR, 1.52; 95% CI, 1.30-1.75; nominal P&lt; 0.0001) Within each treatment arm, median OS was lower for patients with BM compared to patients with no BM for all patients, regardless of PD-L1 status (Table). Patients with BM and PD-L1–high expression, treated with either D or D+T, had numerically higher median OS compared to those with PD-L1 low; this difference was also seen in patients with no BM. In contrast, there was no difference in median OS, for BM or no BM, based on PD-L1 expression for patients treated with SoC (Table). Conclusions: In this post-hoc analysis, presence of BM was significantly and consistently associated with worse outcomes in patients with mUC across all treatment arms of the DANUBE study. PD-L1–high expression was associated with higher median OS in patients treated with D or D+T, regardless of presence of BM. These data reinforce the negative prognostic impact of BM in mUC and the role for PD-L1 expression in predicting benefit for patients treated with ICIs. Funding: AstraZeneca. Clinical trial information: NCT02516241. [Table: see text]

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for patients with stage III-N2M0 non-small cell lung cancer (NSCLC): A population-based study.

8503 Background: Stage III-N2 non-small cell lung cancer (NSCLC) is a heterogeneous disease with controversial management options. Induction therapy as part of multimodal treatment is the standard of care for Stage III-N2 NSCLC. We aim to investigate the effect of adding radiotherapy to neoadjuvant chemotherapy on survival outcomes. Methods: All adult NSCLC patients diagnosed between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database using ICD-O-3 histologic type coding. Inclusion criteria involved stage III NSCLC patients with ipsilateral lymph node involvement (N2), of any T stage, and with no known distant metastasis (M0). Our main sub-cohorts were patients who either underwent chemoradiotherapy (CRT) or chemotherapy (CT) in neoadjuvant settings. Our primary outcomes were overall survival (OS) and cancer-specific survival (CSS) in months. Cox proportional hazards model was used to analyze the effect of each treatment modality on OS and CSS in univariate and multivariate fashions. Multivariate analysis was adjusted for age, sex, marital status, T stage, resected lymph node status, tumor histology, primary site, laterality, and surgical procedure. Inverse probability treatment weighting (IPTW) was applied to create weighted samples based on study covariates. Results: Our analysis included 1175 patients; 799 (68.0%) underwent neoadjuvant CRT and 376 (32.0%) underwent neoadjuvant CT. Sample median age was 63 (IQR:56-69) years. T2 stage was the most prevalent (N =561, 47.7%), followed by T4 (N=243, 20.7%), T1 (N=228, 19.4%), and T3 (N=143, 12.2%). The main tumor histology was non-squamous cell carcinoma in 773 (65.8%) patients. The upper lobe was the most common primary tumor site (N =788, 67.1%). Patients underwent lobectomy (N=917, 78.0%), pneumonectomy (N=184, 15.7%), or sub-lobar resection (N=69, 5.9%). Adding radiotherapy to chemotherapy showed a slightly higher median OS than chemotherapy alone in neoadjuvant settings (51 vs. 47 months, respectively), and a higher median CSS (75 vs. 59 months, respectively). However, these differences were not statistically significant for OS or CSS (HR = 1.08, 95% CI: 0.91-1.28 and HR = 1.04, 95% CI: 0.89-1.21, respectively). After adjustment, age, T3-T4 stage, non-squamous histology, lower lobe primary site, positive resected lymph nodes, and pneumonectomy were all significant independent predictors for worse OS and CSS. IPTW analysis showed no remarkable survival advantage for CRT patients (HR = 1.15, 95% CI: 0.95-1.40 and HR= 1.12, 95% CI: 0.90-1.39) for OS and CSS, respectively. Conclusions: Adding radiotherapy to neoadjuvant CT did not result in significant survival benefits. Multiple prognostic factors should be taken into consideration when identifying the optimal choice and sequence of multimodal treatment for stage III-N2M0 NSCLC patients.

Defining the impact of adjuvant treatment on the prognosis of patients with inoperable glioblastoma undergoing biopsy only: does the survival benefit outweigh the treatment effort?

Patients with inoperable glioblastoma (GBM) usually experience worse prognosis compared to those in whom gross total resection (GTR) is achievable. Considering the treatment duration and its side effects identification of patients with survival benefit from treatment is essential to guarantee the best achievable quality of life. The aim of this study was to evaluate the survival benefit from radio-chemotherapy and to identify clinical, molecular, and imaging parameters associated with better outcome in patients with biopsied GBMs. Consecutive patients with inoperable GBM who underwent tumor biopsy at our department from 2005 to 2019 were retrospectively analyzed. All patients had histologically confirmed GBM and were followed up until death. The overall survival (OS) was calculated from date of diagnosis to date of death. Clinical, radiological, and molecular predictors of OS were evaluated. A total of 95 patients with biopsied primary GBM were enrolled in the study. The mean age was 64.3 ± 13.2 years; 56.8% (54/95) were male, and 43.2% (41/95) female. Median OS in the entire cohort was 5.5 months. After stratification for adjuvant treatment, a higher median OS was found in the group with adjuvant treatment (7 months, range 2–88) compared to the group without treatment (1 month, range 1–5) log-rank test, p < 0.0001. Patients with inoperable GBM undergoing biopsy indeed experience a very limited OS. Adjuvant treatment is associated with significantly longer OS compared to patients not receiving treatment and should be considered, especially in younger patients with good clinical condition at presentation.

Impact of systemic therapy sequencing on overall survival for patients with advanced BRAF-mutated melanoma.

9552 Background: Both immune checkpoint inhibitors (ICI) and BRAF targeted therapy (TT) are effective treatments for patients with advanced BRAF-mutated melanoma. However, the choice of first-line (1L) therapy is at the discretion of treating oncologists without clear guidance from current available data or established guidelines. Utilizing prospectively collected data from the Canadian Melanoma Research Network (CMRN) database, we provide real-world evidence to highlight the impact of sequencing these therapies. Methods: Prospective data from 9 cancer centres in Canada was retrieved from the CMRN database for patients with unresectable/metastatic melanoma, with BRAF targetable subtypes, who received at least one-cycle of 1L palliative-intent ICI or TT, and at least 1-year of follow-up. We categorized patients into 2 groups: 1L BRAF±MEK inhibitors with/without subsequent PD-1±CTLA-4 inhibitors (1L-TT), or vice versa (1L-ICI). The primary study outcome was overall survival (OS). Survival outcomes were analyzed through Kaplan-Meier methods, and multivariable Cox analysis was utilized to account for potential confounders. Results: Our study (N=235) included 152 and 83 patients in 1L-TT and 1L-ICI groups, respectively. Combined BRAF-MEK inhibitors accounted for 59% of the 1L-TT group, whereas single-agent IO accounted for 66% of the 1L-ICI group. There were 93 patients who received second-line (2L) therapy, with a non-significant trend of 1L-TT group receiving more 2L therapy compared to 1L-ICI group (65% vs. 43%, P=0.404). Neither treatment group showed significant differences in median time on 1L therapy (P=0.645) or 2L therapy (P=0.686). The 1L-ICI group was associated with a favourable median overall survival (OS) compared to 1L-TT group (19.3 vs. 10.0 months, P=0.031). Specifically, the ICI only group had the highest median OS, followed by TT-ICI sequence, ICI-TT sequence, and TT only groups respectively (not reached vs. 38.3 vs. 16.9 vs. 6.1 months, P&lt;0.001). However, this OS benefit (HR 0.89, 95% 0.51-1.53, P=0.644) was non-significant upon controlling for confounders such as baseline metastatic sites &gt;2 (HR 2.07, 95%CI 1.24-3.46, P=0.006) and ECOG ≥2 (HR 3.47, 95%CI 2.02-5.97, P&lt;0.001) in multivariable Cox analysis. Conclusions: There was no significant difference in OS between 1L-TT and 1L-IO groups. Rather, OS is driven mostly by the patient’s clinical status and tumour-associated features. Our study provides real-world evidence in an understudied area. Further studies are needed to validate our findings to inform guideline development.[Table: see text]

Peripheral blood eosinophilia may be a prognostic biomarker in non-small cell lung cancer patients treated with immunotherapy.

BackgroundEosinophils have been traditionally associated with the initiation and propagation of inflammatory responses, particularly in allergic diseases and helminth infections. More recently, an association between eosinophils and cancer has been the focus of several studies, but controversial results have emerged. This study aims to evaluate the prognostic role of peripheral blood eosinophilia in non-small cell lung cancer (NSCLC) patients receiving immunotherapy (IO). We also evaluated the impact of peripheral eosinophilia on the occurrence of immune-related adverse effects (irAEs).MethodsAdvanced NSCLC patients under IO were included in a retrospective single-center study. Peripheral blood eosinophilia was defined by a count greater than 500/µL. Patients were analyzed for eosinophil counts, overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR).ResultsA total of 121 NSCLC patients receiving IO were included. Thirty-three (27.3%) patients presented peripheral blood eosinophilia during treatment. Patients with peripheral eosinophilia presented more frequently non-progression as best overall response to IO (83.3% vs. 58.1%, P=0.014), higher median OS (26.6 vs. 9.5 months, P=0.022) and higher median PFS (13.8 vs. 4.6 months, P=0.013). IrAEs were more common in patients with peripheral eosinophilia (66.7% vs. 36.4%, P=0.003).ConclusionsThis study suggests that peripheral blood eosinophilia may predict better outcomes in NSCLC patients receiving IO, despite being associated with an increased risk of irAEs. According to our findings eosinophils may be involved in immune response against tumor. Routine eosinophils count assessment may be an additional prognostic tool in NSCLC patients receiving IO.

Retrospective survival analysis in patients with metastatic pancreatic ductal adenocarcinoma with insulin-treated type 2 diabetes mellitus.

The association between pancreatic ductal adenocarcinoma (PDAC) and type 2 diabetes mellitus (DM2) has long been evaluated and the role of antidiabetic medications such as metformin has also been investigated. The objective of this study was to examine the association between insulin use and overall survival (OS) in patients with advanced PDAC and DM2. We retrospectively collected data from 164 patients, including an exploratory cohort of 96 patients from Medical Oncology Unit, University Hospital and University of Cagliari, Italy, and a validation cohort of 68 patients from Medical Oncology of Modena University Hospital. Patients had metastatic disease and received a first-line gemcitabine-based chemotherapy and, subsequently, a second-line fluoropyrimidines-based chemotherapy. We performed univariate analysis to evaluate correlation between long-term diabetes and overall survival. Then we performed multivariate analysis, adjusting for sex, metastatic sites, Eastern Cooperative Oncology Group Performance Status, Ca19.9 levels, N/L ratio, and lactate dehydrogenase levels at diagnosis, to confirm the independence of the variable. In the exploratory cohort, DM2 was significantly associated with higher median OS at univariate analysis (16 vs 10 months; p = 0.004). This result was confirmed by validation cohort (11 months vs 6 months; p = 0.01). In multivariate analysis, insulin-treated patients compared with non diabetic patients showed a significantly increased survival of 4.6 months (p = 0.03). Patients with insulin-treated metastatic PDAC showed better OS than non diabetic patients, as demonstrated by both cohorts. The correlation between OS and insulin-treated DM2 should be investigated further through a prospective clinical trial.

Real-world use of liposomal irinotecan-based regimens among patients (pts) with metastatic pancreatic adenocarcinoma (mPDAC) in the United States (U.S.).

e16740 Background: The goals of randomized control trials (RCTs) are to make causal inferences and precise treatment comparisons, not to describe large heterogeneous pt populations. RWE allows population-based healthcare decision makers to assess and manage therapeutic and economic options for their pts, including those who would and would not have met inclusion/exclusion criteria of a given RCT and are instead managed under usual care, irrespective of clinical trial protocols. In the pivotal phase 3 trial, NAPOLI-1, 117 pts were treated with liposomal irinotecan + 5-fluorouracil/folinic acid, median age 63 years; 66% were treated first- (1L) or second line (2L), and 91% had performance score ECOG 0 or 1. Pts in the trial had overall survival (OS) of 6.2 months (mos), time to treatment failure (TTF) 2.3 mos, and 27% experienced grades 3-4 neutropenia. The present study describes the patient characteristics and outcomes of pts with mPDAC treated with liposomal irinotecan in the US. Methods: This retrospective observational study used data from Flatiron Health EHR-derived de-identified database from over 280 cancer clinics. Patient characteristics, OS, TTF, and rates of neutropenia during treatment (tx) were assessed in adult pts diagnosed with mPDAC who received liposomal irinotecan based tx between November 1, 2015 and October 31, 2019. Results: 600 pts with mPDAC treated with a liposomal irinotecan based regimen were identified. Of these, 56% were initially diagnosed with stage IV disease, 53% were male, 21% had undergone a previous Whipple procedure, and 61% initiated liposomal irinotecan in the 1L or 2L metastatic setting. Median age at tx initiation was 68 (IQR: 62 – 75) years. 92% of pts were treated in the community setting. Among pts with available ECOG (n = 440), 77.5% were score 0-1. Grade 3/4 neutropenia was observed in 11% (n = 66). Overall, median OS was 5.0 mos [95%CI: 4.2–5.6]. mOS among pts treated in 1L (n = 88), 2L (n = 280), and third line plus (3L+, n = 232) were 6.9 mos [5.3–9.2], 5.4 mos [4.6–6.4], and 4.0 mos [3.4–4.5], respectively. Overall, median TTF was 1.9 mos [1.6–2.1]. TTF by line was 3.5 mos [2.3–4.8] in 1L, 2.1 mos [1.7–2.8] in 2L, and 1.4 mos [1.2–1.6] in 3L. Conclusions: This real-world cohort of pts with mPDAC were older, had worse performance status, and had more prior lines compared to the pivotal trial for liposomal irinotecan. Median OS, TTF, and neutropenia were similar to those previously reported. As expected, pts receiving liposomal irinotecan in earlier lines had higher median OS and TTF.