Search

399 Background: Portal hypertension increases intestinal permeability, dysbiosis, and bacterial translocation, leading to a pro-inflammatory state, which can in turn promote progression of liver disease. However, multiple studies have shown that BB use in patients with cirrhosis can reduce the risk of developing HCC, and in patients with HCC, BB can improve overall survival (OS). In recent years, ICIs have become first-line therapy for patients with unresectable HCC, and we aimed to evaluate whether BB use conferred survival benefits in patients treated with ICIs using real-world data. Methods: We conducted a retrospective chart review of HCC patients treated with ICI from 2017 to 2019 at 13 institutions across North America, Europe, and Asia in order to evaluate the association between BB use and OS, as well as BB use and overall response rate (ORR). Univariable and multivariable logistic regression models were used to evaluate associations, and survival analyses were performed using the Kaplan-Meier method. Results: A total of 578 patients were evaluated. The median age of the cohort was 65 years, and 80% of patients were male. The majority of patients (70%) were cirrhotic. The causes of underlying liver disease were as follows: HBV (22%), HCV (36%), alcohol (20.8%), and NASH (13%). Most patients (73.5%) had Child Pugh (CP) class A liver disease, and good performance status with ECOG score either 0 (52%) or 1 (45%). The majority of patients (75%) treated with ICIs received a PD-1 inhibitor alone. There were 360 deaths (62% of patients) with a median follow-up of 30.8 months (Quartiles: 17.2-40.3 months). Two hundred and three (35%) patients had BB use at any point during ICI therapy. Fifty-one percent of these patients were on a nonselective BB whereas 49% were taking a cardio-selective BB. BB use was not significantly correlated with OS (hazard ratio, 1.12; 95% CI, 0.9-1.39; P = 0.298) or ORR (odds ratio, 0.84; 95% CI, 0.54-1.31; P = 0.451) in univariate or multivariate analyses. Conclusions: Patients who used BB while on immunotherapy for unresectable HCC did not have statistically significant differences in OS or ORR compared to patients who did not use BB. More studies are required to elucidate the effect of beta blockade on the microbiome, immune activation, and HCC.

393 Background: Atezolizumab plus bevacizumab (A+B) is the new standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). No evidence exists as to its use in routine clinical practice in patients (pts) with impaired liver function. Methods: This retrospective, multi-center observational study was conducted across 7 tertiary academic referral centres and collected 64 HCC pts consecutively treated with A+B. Efficacy outcome measures included overall (OS) and progression-free survival (PFS) calculated from time of A+B commencement and overall response rates (ORR) and disease control rates (DCR) defined by Response Evaluation Criteria in Solid Tumors (RECIST, v1.1). Safety outcomes included treatment-related adverse events (trAEs) graded (G) according to CTCAE v5.0. Results: Of 64 eligible pts, 54 had BCLC C stage HCC (84%), secondary to hepatitis C cirrhosis (n = 24; 37%), hepatitis B (n = 10; 16%), and non-viral etiologies (n = 40; 47%). Liver function was classified as Child-Pugh (CP) A in 46 patients (72%), B7 in 7 (11%), B8 in 8 (12%), and B9 in 3 (5%). Patients were of performance status (PS) ECOG 0 (n = 39; 61%) and 1 (n = 25; 39%). Pre-treatment upper-gastrointestinal endoscopy was performed in 44 patients (69%), with gastro-esophageal varices found in 18 pts (40%) and graded as 1 (n = 12, 27%), 2 (n = 4, 9%) and 3 (n = 2, 4%) respectively. After a median follow-up of 6.8 months (m) (95% confidence interval [CI], 5.5-8.0), median OS (mOS) was 11.7m (95% CI, 6.2-17.3) whereas median progression-free survival (mPFS) was 6.97m (95% CI, 2.9-11.0). ORR and DCR were 26% and 62% respectively. TrAEs of any grade were documented in 43 pts (67%): 12 pts (18%) had trAEs of G≥3: 7 (11%) atezolizumab-related and 5 (8%) bevacizumab-related. Toxicity led to treatment discontinuation in 3 pts (5%). Compared to CP-A, CP-B pts achieved shorter OS (11.7m [95% CI, 10.3-13.2] vs 6.5m (95% CI, 3.5-9.5), p = 0.029) and PFS (9.1m [95% CI, 5.4-12.8] vs 2.3m [95% CI, 1.7-2.9], p = 0.001) with no differences in ORR nor in DCR. The rate of trAEs did not significantly differ across CP classes. Median OS was significantly longer in patients achieving a radiologic response (12.7m [95% CI, not reached] vs 11.0m [95% CI, 5.5-16.5], p = 0.04). Presence and grade of varices was not associated to bevacizumab-related trAEs. Conclusions: This study confirms reproducible efficacy and safety of A+B in routine practice. Despite inferior OS and PFS compared to CP-A, A+B was associated with similar tolerability and radiologic response in CP-B patients, warranting prospective evaluation of A+B in this treatment deprived population.

Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m2 days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles. The primary end point of the study was to improve disease-free survival (DFS) from 14 to 18 months by adding erlotinib to gemcitabine. Results In all, 436 patients were randomly assigned at 57 study centers between April 2008 and July 2013. A total of 361 instances (83%) of disease recurrence were observed after a median follow-up of 54 months. Median treatment duration was 22 weeks in both arms. There was no difference in median DFS (GemErlo 11.4 months; Gem 11.4 months) or median overall survival (GemErlo 24.5 months; Gem 26.5 months). There was a trend toward long-term survival in favor of GemErlo (estimated survival after 1, 2, and 5 years for GemErlo was 77%, 53%, and 25% v 79%, 54%, and 20% for Gem, respectively). The occurrence or the grade of rash was not associated with a better survival in the GemErlo arm. Conclusion To the best of our knowledge, CONKO-005 is the first study to investigate the combination of chemotherapy and a targeted therapy in the adjuvant treatment of PDAC. GemErlo for 24 weeks did not improve DFS or overall survival over Gem.

158 Background: The multi-kinase inhibitor regorafenib (REGO) and oral fluoropyrimidine TAS-102 (TAS) show efficacies as single agents in treatment of refractory metastatic CRC patients (pts). We conducted a conventional 3+3 dose finding to determine a recommended phase II dose (RP2D) of its combination REGOTAS and efficacy in 3-4.-line. Methods: Eligible patients with ECOG 0-1, measurable mCRC, not amenable to surgery had at least 3rd-line treatments. Prior fluoropyrimidine-based and anti-VEGF (R) combinations were mandatory, and anti-EGFR for RAS WT tumors. TAS was given on days 1-5 and 8-12 (28-days cycle); REGO on days 2-22 (dose levels see table below). The following major AE categories were used to define DLTs if they occurred during the first 2 treatment cycles: any grade ≥3 non-hematologic toxicity (except vomiting, nausea, non-significant lab abnormalities), grade ≥3 hematological toxicities, grade ≥3 bleeding. Tumor response was assessed Q8W as per RECIST1.1. EudraCT 2016-001968-11; NCT03305913. Results: All observed toxicities were consistent with safety profile of individual IMPs. 6 pts were enrolled into each DL1 and DL2 (n=12 in total). One DLT was observed in 1/6 pts in DL1; 2 DLTs in 2/6 pts in DL2. All DLTs were only grade 3 hypertension was well manageable, causality was attributed to REGO. No DLT resulted in treatment discontinuation. Results indicate a RP2D of 25mg/m² TAS-102 BID + 120mg REGO daily. No remissions were observed. Overall disease control rate (DCR) after 8 weeks was promising with 58.3% (DCR of 33.3% for DL1 and 83.3% in DL2) and remarkably better as historical data with 41/44% for REGO/TAS102 alone, respectively (Lancet 2013/NEJM 2015). Conclusions: Toxicities of REGOTAS were consistent with safety profiles of REGO and TAS alone. No additional DLTs were attributed to REGOTAS. Thus, the risk-benefit assessment of REGOTAS was positive. DCR was clinically quite meaningful. Mature PFS and OS will be presented at the meeting. Clinical trial information: NCT03305913. [Table: see text]

e15651 Background: Portal vein invasion (PVI) is has a significant impact on the prognosis of patients with hepatocellular carcinoma (HCC). Patients with PVI are classified as stage C in the BCLC score and systemic therapy is recommended. Patients with minor PVI are frequently misclassified due to radiological challenges in determining malignant PVI or non-adherence to guidelines. The concept of resection or TACE in limited PVI is sometimes followed with the assumption of a negligible influence on survival. Aim of this study is the reevaluation of PVI and the analysis of the impact of a misclassification. Methods: 763 patients with HCC of a total of 1413 were extracted from the clinical registry of our tertiary center as an ongoing effort to reevaluate the extent of PVI in all patients treated between 1/1/2000 and 12/31/2015. PVI was diagnosed by re-evaluating all available CT or MRI scans by an experienced liver imaging radiologist. PVI was documented using the Liver Cancer Study Group of Japan classification ranging from Vp0-Vp4: Vp0 = no PVI; Vp1 = segmental; Vp2 = right anterior or posterior PV; Vp3 = right or left PV; Vp4 = main trunk. The influence on survival was calculated for each BCLC stage. Results: 259 patients (pat) were classified with PVI. Median age at diagnosis was 65.3 years, 213 patients (82.2%) were male. Etiology of liver disease was alcohol (43.6%), viral hepatitis (29.8%), NASH (5.8%), and others (10.4%). No liver disease was present in 18 pat (6.9%). No liver cirrhosis (LCI) was present in 32 pat (12.4%). LCI was classified as Child Pugh stage A/B/C in 65 (25.1%)/109 (42.1%) and 52 (20.1%) of patients. BCLC classification prior to reevaluation in pat with new PVI was A/B/C/D in 9/13/164/71 of cases. Comparing the overall survival (OS) of pat initially classified as BCLC A with or without PVI was 21.3 months vs. 106.4 months (p = 0.001), in BCLC B the OS was 11.0 months vs. 37.7 months (p = 0.001). Conclusions: Even minor PVI leads to dismal prognosis. Meticulous evaluation of cross sectional imaging is crucial for the clinical management of patients with HCC. Once PVI has been diagnosed, such patients have to be classified as advanced stage. The guidelines should be followed closely, irrespective of the extent of PVI.

Purpose To perform an external validation of the Assessment for Retreatment with Transarterial Chemoembolization (ART) and α-fetoprotein (AFP), Barcelona Clinic Liver Cancer (BCLC), Child–Pugh, and response (ABCR) scores and to compare them in terms of prognostic power. Materials and Methods From 2000 to 2015, 871 patients with hepatocellular carcinoma underwent transarterial chemoembolization at a tertiary referral hospital, and 176 met all inclusion and exclusion criteria for both scores and were analyzed. Nineteen percent (n = 34) had BCLC stage A disease and 81% had stage B disease. Thirty-nine patients (22%) presented with elevated AFP levels. Overall survival was calculated. Scores were validated and compared with a Harrell C-index, integrated Brier score (IBS), and prediction error curves. Results Before the second chemoembolization procedure, 22 patients (12%) showed an increase of 1 point in Child–Pugh score and 51 patients (22%) had an increase of ≥ 2 points. Thirty-one patients (23%) showed a > 25% increase in aspartate aminotransferase level, and 114 (65%) showed a response to treatment. Consequently, 127 patients (72%) had a low ART score and 49 (28%) had a high ART score. One hundred fifty-eight patients (90%) had a low ABCR score, whereas 18 (10%) had a high ABCR score. Low and high ART score groups had median survival durations of 20.8 and 15.3 mo, respectively. Harrell C-indexes were 0.572 and 0.608, and IBSs were 0.135 and 0.128, for ART and ABCR, respectively. For both scores, an increase in Child–Pugh score ≥ 2 points and a radiologic response were significantly associated with survival. Conclusions Both scores were of limited predictive value, and neither was sufficient to support clear-cut clinical decisions. Further effort is necessary to determine criteria for making valid clinical predictions.

4007 Background: Adjuvant chemotherapy with gemcitabine (Gem) for 6 months significantly improves survival of pancreatic cancer patients. CONKO-005 was designed to evaluate an additional effect of ...

140 Background: S-1 (Teysuno), an oral fluoropyrimidine registered in Europe since 2011, provides a good efficacy and safety profile for the treatment (trt) of AEGC in combination with cisplatin. (FLAGS Study; J.A. Ajani. EJC2013). Because triplets with platinum compounds and anthracyclines are commonly used in AEGC, a phase I evaluating S-1 with fixed doses of oxaliplatin (130 mg/m² D1) and epirubicin (50 mg/m² D1) q3w in AGIC pts [cohorts 1 (C1) and 2 (C2)] and in chemonaïve AEGC pts [cohort 3 (C3)] was performed. Methods: Pts >18 years, ECOG/PS 0/1 were enrolled. Standard dose-limiting toxicity (DLT) evaluation was used. The maximum tolerate dose (MTD) was defined as the highest dose level at which less than