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293 Background: NET-02 was a multi-centre, randomised (1:1), non-comparative phase II trial of nal-IRI/5-FU/folinic acid (ARM A) or docetaxel (ARM B) in pts with progressive PD-EP-NEC, aimed at selecting a treatment for evaluation in a phase III trial. Primary analysis (N = 58) showed ARM A, but not ARM B, achieved the target 6-month progression-free survival rate primary endpoint (McNamara et al. ASCO 2022). HRQoL was a secondary endpoint in NET-02. Methods: HRQoL was assessed using the EORTC QLQ-C30 and GINET21 (at baseline (BL), 6-weekly intervals and at disease progression). The mean change from BL was estimated for each scale by timepoint and treatment arm. Results are presented where there were ≥4 responses per time point. Scores were considered stable if they did not change by > 10 points from BL. The mean BL C30 scores for all pts were compared to United Kingdom (UK) population normative C30 data using a 2-sample t-test. Results: Fifty-four of 58 pts (93%) completed a BL questionnaire; of these, 39 (72%) completed ≥1 post-BL questionnaire, with 21 (51%) completing questionnaires at progression. Global health status (GHS) and all functional scales in ARM A remained stable from BL to intervals pre-progression, with a sustained improvement in role functioning observed post-BL. In ARM B, GHS and all C30 functional scales decreased by > 10 points between BL and week 18 (worsening of QoL). Both arms had a > 10-point increase from BL in constipation and diarrhoea in ≥1 post-BL time point. In ARM A, pain, insomnia and financial problems decreased from BL. No C30 symptom scales in ARM B were consistently lower post-BL. Patterns of change in GINET21 mean score were similar in both arms: body image, disease-related worries, information/communication, sexual function and social function all had a > 10-point reduction in score from BL (indicating improvement in symptoms/problems); endocrine and gastrointestinal symptoms remained stable; muscle/bone pain varied across time points, initially showing a reduction in pain followed by an increase, compared to BL. In comparison to the UK C30 norms (BL all pts), 11 of 15 C30 scales did not significantly differ (P > 0.05). Mean scores for fatigue and appetite loss were significantly higher than UK C30 norms (worse symptoms in pts from NET-02) (P = 0.03, P = 0.0003 respectively). However, emotional functioning and GHS were significantly better in pts from NET-02 (P = 0.001, P = 0.03 respectively). Role and social functioning were lower in pts from NET-02 (both P = 0.06) (poorer level of functioning). Conclusions: HRQoL was maintained and potentially improved with nal-IRI/5-FU/folinic acid, but not docetaxel. Compared to the UK general population, BL QoL did not substantially differ in pts from NET-02. Clinical trial information: NCT03837977.

4016 Background: Rivaroxaban thromboprophylaxis has been shown to reduce venous thromboembolism (VTE) on-treatment in ambulatory cancer patients in a recent randomized trial. Pancreatic cancer patients are at substantial risk for VTE; value of thromboprophylaxis has not been definitively established. Methods: CASSINI was a double-blind placebo-controlled trial of cancer patients initiating a new regimen, at high risk for VTE (Khorana score ≥2), randomized to rivaroxaban 10 mg daily or placebo up to 180 days. Patients were stratified by presence or absence of pancreatic cancer. Patients had screening ultrasound and blood drawn at baseline and every 8 wks. Primary efficacy endpoint was a composite of symptomatic DVT, asymptomatic proximal DVT, any PE and VTE-related death. Primary safety endpoint was International Society on Thrombosis and Hemostasis (ISTH)-defined major bleeding. Results: Of 1080 patients enrolled, 49 (4.5%) failed screening due to baseline VTE, with even higher rates [24/362 (6.6%)] in patients with pancreatic cancer. Of 841 randomized patients, 273 (32.6%) had pancreatic cancer with median age 66 y; 57% male and 155/273 (57% in each arm) completing the double-blind period. During intervention (on-treatment) period, 5/135 (3.7%) pancreatic cancer patients in the rivaroxaban arm and 14/138 (10.1%) in placebo arm had primary endpoint events [HR 0.35; 95%CI (0.13, 0.97), p = 0.03; number needed to treat, NNT = 16]. Major bleeding was not increased, occurring in 2 (1.5%) patients in rivaroxaban arm and 3 (2.3%) in placebo arm. Further benefit with rivaroxaban was observed when including primary and secondary endpoints (arterial/visceral events): 6/135 (4%) events in rivaroxaban vs 17/138 (12%) in placebo [HR, 0.34; 95%CI (0.14, 0.87), P = 0.02; NNT = 13]. Correlative biomarker studies demonstrated significant decline in D-dimer values over time (weeks 8 and 16) in patients without VTE randomized to rivaroxaban prophylaxis compared to placebo (P < 0.01), supporting clinical findings. Conclusions: Rivaroxaban substantially reduced VTE in pancreatic cancer patients during intervention period. Given no increase in major bleeding, our findings suggest benefit to rivaroxaban thromboprophylaxis in pancreatic cancer patients initiating systemic therapy. Clinical trial information: NCT02555878.

4109 Background: Biliary tract cancers (BTCs) encompass both cholangiocarcinoma (CC), arising in intrahepatic, perihilar (klatskin), or distal biliary tree, ampulla of vater and gallbladder carcinoma (GBC). Prognosis is poor for majority of these patients (pts). Aim: To retrospectively review outcomes of pts, as practices/treatments evolve, who presented to a multidisciplinary team at tertiary referral center Princess Margaret Hospital, Toronto, with a diagnosis of BTC. Methods: 1057 pts were followed from 01/87 - 09/11. Complete demographics, performance status (PS), disease site, histological diagnosis, percentage receiving surgery with curative intent, chemotherapy (CT), radiotherapy (RT), recurrence patterns and overall survival (OS) were analyzed. Results: The cohort includes 549 (52%) males, PS of 0-1 in 850 (80%), 2-3 in 87 (8%) pts. A histological diagnosis of adenocarcinoma was confirmed in 885 (84%), 106 (10%) non diagnostic, 66 (6%) other. Definitive surgery was performed in 41% and adjuvant CT or concurrent CT/RT given in 20% and 8% respectively. CT or CT/RT was given for unresectable/metastatic disease in first line palliative setting in 395 (37%) and 18 pts (5%) respectively. Response to first line CT in GBC was 33% vs. 24% in CC (p=0.005) and med survival was 8.4 and 13.1 mo respectively (p=0.001). The OS for entire cohort of 1057 pts was 19.3 mo with survival for breakdown of tumor type, stage detailed in the table. At this time, 207 (20%) are still alive, 609 (58%) deceased, status unknown/pending in 241 (22%). Conclusions: This represents a large biliary cancer cohort with survival benchmarks obtained in modern era of multidisciplinary care. Different subsites clearly present at different stages and have different prognosis with treatments. Despite better responses for advanced disease on CT in GBC, survival was better in CC consistent with reported literature. Therapeutic advancement mandates finding additional drug options and appropriate adjuvant care. [Table: see text]

646 Background: As demonstrated in the primary analysis of NET-02, nal-IRI/5-FU/folinic acid, but not docetaxel, met the primary endpoint of 6 month (mo) progression-free survival (PFS) rate in pts with progressive PD-EP-NEC. Here, the final results are presented. Methods: This was a multi-centre, randomised (1:1), phase II trial of IV nal-IRI (70mg/m2 free base)/5-FU (2400 mg/m2)/folinic acid, Q14 days (ARM A), or IV docetaxel (75mg/m2), Q21 days (ARM B), as 2L therapy in pts with progressive PD-EP-NEC, aimed at selecting a treatment for continuation to a phase III trial. On disease progression, pts in both arms could receive further systemic treatment as recommended by their physicians. Primary endpoint was 6 mo PFS rate; 80% power to demonstrate the one-sided 95% confidence interval (CI) of the 6 mo PFS rate excluded 15%, if the true rate was ≥30% (required level of efficacy); a rate of

4005 Background: The prognosis for pts with PD-EP-NEC is poor. A recognised first-line (1L) treatment for advanced disease is etoposide/platinum-based chemotherapy; there is no standard second-line (2L) treatment (area of unmet need). Methods: This was a multi-centre, randomised (1:1), phase II trial of IV nal-IRI (70mg/m2 free base)/5-FU (2400 mg/m2)/folinic acid, Q14 days (ARM A), or IV docetaxel (75mg/m2), Q21 days (ARM B), as 2L therapy in a planned 102 pts with progressive PD-EP-NEC, aimed at selecting a treatment for continuation to a phase III trial. Pts with histologically-confirmed PD-EP-NEC (Ki-67>20%; Grade 3, WHO 2019), who had prior 1L platinum-based chemotherapy and radiological disease progression or discontinuation of 1L therapy due to intolerance, with an ECOG performance status ≤2 were eligible. Randomisation was stratified by Ki-67, ECOG PS, presence of liver metastases, and response to previous platinum-based therapy. Primary endpoint was 6 month (mo) progression-free survival (PFS) rate; 80% power to demonstrate the one-sided 95% confidence interval (CI) of the 6 mo PFS rate excluded 15%, if the true rate was at least 30%, where 30% was the required level of efficacy; a rate of