2325 A study of the representativity of the NCIC, PRODIGE and MPACT phase III trials of gemcitabine-erlotinib, FOLFIRINOX and gemcitabine-nab-paclitaxel in patients with advanced pancreatic cancer treated in a real-life setting

Abstracts 2325 POSTER A study of the representativity of the NCIC, PRODIGE and MPACT phase III trials of gemcitabine-erlotinib, FOLFIRINOX and gemcitabine-nab-paclitaxel in patients with advanced pancreatic cancer treated in a real-life setting D. Aknoundova1 , R. Diaz Beveridge1 , C. Escoin1 , A. Segura1 , G. Bruixola1 , E. Reche1 , A. Gimenez1 , C. Salvador1 , O.M. Nino ˜ 1 , J. Aparicio1 . 1 University Hospital La Fe, Medical Oncology Department, Valencia, Spain Background: Recent phase III trials in patients with advanced pancreatic adenocarcinoma have reported that the combination of gemcitabine and nab-paclitaxel, FOLFIRINOX and, to a lesser extent, the combination of gemcitabine and erlotinib are superior with regards to overall survival to gemcitabine monotherapy. However, the benefits seen with these combination regimens are in general slim, the inclusion and exclusion criteria were fairly strict and it is not clear if the patients in these trials were representative of the whole advanced pancreatic adenocarcinoma population. Methods: Retrospective review of 211 consecutive patients (pts) diagnosed from 2006 to 2015 at our institution with locally advanced unresectable or metastatic pancreatic cancer. Potential eligibility for entry to the landmark phase III trials of gemcitabine-erlotinib (NCIC), FOLFIRINOX (PRODIGE) and nab-paclitaxel plus gemcitabine (MPACT) was assessed. Overall survival (OS) was calculated with the Kaplan–Meier function, while differences in OS between subgroups were assessed with the log-rank test. Results: 121 (57%) pts matched all of the inclusion and exclusion criteria for the gemcitabine-erlotinib trial, 50 (24%) for nab-Paclitaxel plus gemcitabine and 34 (16%) for FOLFIRINOX. Ineligibility for FOLFIRINOX was due to ECOG performance status (PS) 2 (44%), non-metastatic disease (35%) and bilirubin >1.5× upper limit of normality (ULN) (25%). The main reasons for nab-paclitaxel plus gemcitabine ineligibility were Karnofsky score <70 (31%), non-metastatic disease (35%) and bilirubin >ULN (27%). Pts were not suitable for gemcitabine-erlotinib mainly due to poor liver function (25%) and PS >2 (15%). With a median (m) follow-up of 65.3 mts (r 16–116 mts), the mOS of the whole cohort was 5.9 mts (95% IC 5.0−6.8). For pts who received gemcitabine, gemcitabine-erlotinib, nab-paclitaxel-gemcitabine and FOLFIRINOX, mOS was 6.7 mts (95% CI 0.0–16.1), 6.6 mts (95% CI 4.0−9.1), 24.7 mts (95% CI NR) and 10.7 mts (95% CI 9.1–12.3), respectively (p < 0.001). FOLFIRINOX-eligible pts had longer mOS than the FOLFIRINOX-ineligible pts (7.3 vs. 5.7 mts, p < 0.05), However, there were no differences in mOS between pts eligible or not for gemcitabinenab-Paclitaxel (5.8 vs. 5.9 mts, p > 0.05). Conclusions: Less than a quarter of our patients with advanced pancreatic cancer would have been eligible for entry into the PRODIGE and MPACT trials. Poor PS, locally advanced disease and bilirubin abnormalities were the main reasons. Although more patients were eligible for erlotinib, it showed little activity compared to gemcitabine alone. Novel therapies or dose-reduced regimen trials for frail, icteric or elderly patients and subgroup-specific trials for patients with locally advanced disease, with or without radiotherapy, are urgently needed. No conflict of interest. 2326 POSTER An internally validated new clinical prognostic score for patients with advanced hepatocellular carcinoma treated with sorafenib ˜ 1 , E. Reche1 , C. Salvador1 , G. Bruixola1 , R. Diaz Beveridge1 , O.M. Nino C. Escoin1 , D. Akhoundova1 , A. Segura1 , A. Gimenez1 , J. Aparicio1 . 1 University Hospital La Fe, Medical Oncology Department, Valencia, Spain Background: Sorafenib (S) is the standard 1st-line treatment for advanced hepatocellular carcinoma patients (pts). Liver function and performance status (PS) are the main prognostic factors. Among other novel prognostic factors, a low baseline neutrophil-to-lymphocyte ratio (NLR) and early-onset diahrroea with S have been linked with a better prognosis. Our aim was to identify prognostic factors in pts treated with S and to develop a prognostic scoring system in order to better differentiate patient risk groups. Material and Methods: Retrospective review of 145 S-treated pts at our institution (2008–2014). Baseline NLR, overall toxicity, early toxicity rates (onset in 1st 30 days), overall survival (OS) were assessed. Univariate and multivariate analysis of prognostic factors for OS was performed. The prognostic score was calculated from the regression coefficients found in the Cox regression analysis. Bootstrapping, time-dependent receiver operating characteristic curves and pseudoR2 index were used for internal validation. Results: Baseline characteristics shown in Table 1. The optimal NLR cutoff for OS prediction by ROC analysis was 4 (AUC 0.62). With a median

S441 follow-up of 43 months (mts), median (m) PFS and OS was 4.15 (95% CI 2.5−5.8) and 6.7 mts (95% CI 4.5−8.8), respectively, with a 1-year OS of 33%. Independent prognostic factors in the multivariate analysis for OS were PS 1−2 vs 0 (HR 2.070, p < 0.0001), Child-Pugh (C-P) score B vs A (HR 1.920, p 0.005), early-onset diarrhoea (all grades, HR 0.686, p 0.006) and NLR >4 (HR 1.767, p 0.011). The prognostic score based on these four variables was found efficient (Cox-Snell and Nagelkerke index 0.86; Mann–Whitney z −2.83, p.005). Four risk groups were identified: a very low-risk group (mOS 25.83 mts, 95% CI 0−99), a low-risk group (mOS 15.55 mts, 95% CI 7.6–23.4), an intermediate-risk group (mOS 7.35 mts, 95% CI 4.7−9.9) and a high-risk group (mOS 3.93 mts, 95% CI 1.2−6.6). Conclusions: PS and C-P score were the main prognostic factors in predicting survival, followed by early-onset diahrroea and a low baseline NLR. We identified four risk groups for OS based on these four parameters. This simple prognostic model could be useful for patient risk-stratification, but an external validation in a larger population is needed. Characteristics

n (%)

Median age (range) Performance status 0 1−2 Male sex Cirrhosis Child–Pugh score A B Barcelona Clinic Liver Cancer staging (BCLC) B C Portal vein thrombosis Distant metastasis Prior local therapies NLR score <4 Early diarrhoea (all grades) Modified Prognostic Score 0 points, very low-risk 1 point, low-risk 2 points, intermediate-risk 3−4 points, high-risk

62 (26−82) 33 (22.8) 112 (77.2) 109 (75.2) 118 (81.4) 106 (73.1) 39 (26.9) 25 (17.2) 120 (82.8) 52 (35.9) 78 (54) 86 (61) 95 (69.9) 61 (42.4) 9 (6.2) 36 (24.8) 61 (42.1) 30 (26.9)

No conflict of interest. 2327 POSTER Comparison between Child Pugh A5 vs A6 and ALBI grade 1 vs 2 in patients treated with sorafenib for HCC J. Edeline1,2 , J.F. Blanc3 , P. Johnson4 , P. Ross5 , Y.T. Ma6 , J. King7 , R. Hubner8 , J. Graham9 , S. Darby10 , J. Evans11 , C. Iwuji12 , D. Swinson13 , P. Collins14 , K. Patel15 , I. Muazzam16 , D. Palmer17 , T. Meyer2 . 1 Centre ` Eugene Marquis, Oncologie, Rennes, France; 2 University College ˆ ´ London, Oncology, London, United Kingdom; 3 CHU Hopital Saint-Andre, Hepatology, Bordeaux, France; 4 University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Liverpool, United Kingdom; 5 King’s College Hospital, Oncology, London, United Kingdom; 6 University Hospital Birmingham, Oncology, Birmingham, United Kingdom; 7 Royal Free Hospital, Oncology, London, United Kingdom; 8 The Christie NHS Foundation Trust, Oncology, Manchester, United Kingdom; 9 The Newcastle upon Tyne NHS Foundation Trust, Oncology, Newcastle upon Tyne, United Kingdom; 10 Sheffield Teaching Hospitals NHS Foundation Trust, Oncology, Sheffield, United Kingdom; 11 University of Glasgow, Beatson West of Scotland Cancer, Oncology, Glasgow, United Kingdom; 12 Leicester Royal Infirmary, Oncology, Leicester, United Kingdom; 13 Leeds Teaching Hospitals NHS Trust, Oncology, Leeds, United Kingdom; 14 University Hospitals Bristol NHS Foundation Trust, Oncology, Bristol, United Kingdom; 15 Oxford University Hospitals NHS Trust, Oncology, Oxford, United Kingdom; 16 Hull and East Yorkshire Hospitals NHS Trust, Oncology, Hull, United Kingdom; 17 Cancer Research UK Centre, University of Liverpool, Oncology, Liverpool, United Kingdom Background: The ALBI grade was proposed as an objective means to evaluate liver function in patients with Hepatocellular Carcinoma (HCC). The grade is calculated using a formula requiring only albumin and bilirubin values, and three prognostically distinct categories are defined. ALBI grade 1 vs 2 were proposed as stratification factors within the Child Pugh (CP) A class. However, the original publication did not provide comparison with the sub-classification by A5 vs A6 of the CP classification. Here, we compare