bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) treated with chemotherapy (CT): The British Columbia Cancer Agency (BCCA) mCRC score.
Authors: Chen Leo , Gresham Gillian , Cheung Winson Y. , Kennecke Hagen F. , Renouf Daniel John
Published: March 2020

3624

Background: The prognosis of individual pts with mCRC can be highly variable. Our objective was to develop a scoring system to improve the prognostication of mCRC pts at baseline assessment. We also further explored the impact of palliative resection (PR) of the primary tumor on OS. Methods: Pts diagnosed with mCRC from 2006 to 2008, referred to 1 of 5 regional cancer centers in British Columbia were retrospectively reviewed. Pts with prior early stage CRC who relapsed with mCRC were excluded. Multivariate stepwise selection was performed using significant variables from univariate analysis. Patients were assigned a composite risk score (range 0-15) based on their baseline variables, and then separated into quartiles for OS using cut-point analysis and Kaplan Meier methods. A secondary propensity score matched analysis was performed to obtain hazard ratios (HR) for death in order to control for baseline differences between pts who underwent PR and those who did not. Results: A total of 505 mCRC pts were included: median age 63 (range 22-86), 58% male, 75% ECOG 0-1, 58% colon primary, 34% >1 metastatic site, and 46% smokers. In this cohort, 81% of the population underwent PR. ECOG 2-3, no primary resection, colon primary, >1 metastatic site, CEA level >4 ng/ml, male gender, and smoker were significant in the multivariate model and subsequently assigned a score. Median OS varied significantly depending on the composite risk score (table). After ECOG PS, PR of the primary was the second strongest prognostic factor (HR 2.3, 95%CI 1.6-3.3). To further explore this, a propensity score matched analysis was performed adjusting for age, gender, ECOG and receipt of chemotherapy. Prognosis continued to be more favorable in the PR group with a median OS of 17 vs. 7.9 months (HR 0.66, 95% CI 0.50-0.86, p=0.0019). Conclusions: In this population based analysis, the BCCA mCRC score was a simple and effective method to improve prognostication for mCRC pts. PR of the primary was associated with significantly longer OS. [Table: see text]
A phase I study of sorafenib with FOLFIRI as first-line therapy for metastatic colorectal cancer (mCRC): Safety and efficacy results.
Authors: Maroun Jean Alfred , Jonker Derek J. , Cripps M. Christine , Asmis Timothy R. , Goel Rakesh , Goodwin Rachel Anne , Marginean Horia
Published: March 2020

3633

Background: Phase I dose escalation to a maximum planned dose (MPD) o determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), recommended-phase-II-dose (RP2D) and preliminary efficacy of sorafenib and FOLFIRI (irinotecan reduced-dose) in metastatic colorectal cancer (mCRC) patients. Methods: Starting doses: irinotecan 80 mg/m2 iv d1, sorafenib 400 mg po twice daily (bid, continuous), starting day 2. Escalations based on toxicity observed at the previous dose level (DL) up to: irinotecan 100 mg/m2 and sorafenib 800 mg bid. DLT was evaluated within the 1st study cycle (1 cycle = 2 FOLFIRI treatments). Results: 5 cohorts were concluded. All 16 ECOG PS 0-1 patients (9/7 men/women; 2/14 rectal/colon) with median age of 64, discontinued study: 10 (62%) disease progression, 4 (25%) toxicity, 1 curative surgery, 1 comorbidities. The dose levels of irinotecan (mg/m2, day1) and sorafenib (mg/day, bid, day 2-28) studied were DL1-80/400, DL2-80/600, DL3-90/600, DL4-100/600 and DL5-100/800, repeated every 4 weeks, 3 patients/DL. No DLT was observed. The MTD was not reached at the MPD (DL5). The most common ≥Gr2 treatment related adverse events (AEs) were: neutropenia 81%, HFS 69%, leucopenia 50%, fatigue 38%, anemia 31%, constipation 31%, nausea/vomiting 31%, mucositis 31%, diarrhea 25%, hypophosphatemia 25%. The most severe treatment related AEs were: Gr4: neutropenia 2 (12.5%); pulmonary embolism 1 (6%); Gr3: HFS 9 (56%), neutropenia 3 (19%), leucopenia 3 (19%), hypophosphatemia 3 (19%). Objective response rate was 56% (9 of 16 patients, 95%CI; 33-77%). Response duration was 13 months (95%CI; 5-17). Median progression-free survival and overall survival were 11 months (95%CI; 6-17) and 25 months (95%CI; 15-34), respectively. Conclusions: Combination therapy with S and modified FOLFIRI in these patients is well tolerated and demonstrates clinical efficacy at the MPD. The MTD was not reached at the MPD. Future research of this combination is warranted. Supported by Bayer Healthcare Pharmaceuticals. Clinical trial information: NCT00780169.
Results of a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas with PET and CA19-9 correlates.
Authors: Von Hoff Daniel D. , Ervin Thomas J. , Arena Francis P. , Chiorean E. Gabriela , Infante Jeffrey R. , Moore Malcolm J. , Seay Thomas E. , Tjulandin Sergei , Ma Wen Wee , Saleh Mansoor N. , Harris Marion , Reni Michele , Ramanathan Ramesh K. , Tabernero Josep , Hidalgo Manuel , Van Cutsem Eric , Goldstein David , Wei Xinyu , Iglesias Jose Luis , Renschler Markus Frederic
Published: March 2020

4005^

Background: nab-paclitaxel (nab-P; 130 nm albumin-bound paclitaxel) has demonstrated both single-agent activity and synergy with gemcitabine (G) in preclinical models of pancreatic cancer (PC). nab-P + G also demonstrated promising efficacy in a phase I/II study in metastatic PC (J Clin Oncol. 2011:4548-4554), warranting a phase III study of nab-P + G vs G for metastatic PC. Methods: 861 patients (pts) with metastatic PC and a Karnofsky performance status (KPS) ≥ 70 were randomized at 151 community and academic centers 1:1 to receive nab-P 125 mg/m2 + G 1000 mg/m2 days 1, 8, and 15 every 4 weeks or G alone 1000 mg/m2weekly for 7 weeks followed by 1 week of rest (cycle 1) and then days 1, 8, and 15 every 4 weeks (cycle ≥ 2). The primary endpoint was OS; secondary endpoints were PFS and ORR by independent review. Results: The median age was 63 years (range 27 - 88). KPS was 100 (16%), 90 (44%), 80 (32%), and 70 (7%). Pts had advanced disease with liver metastases (84%), ≥ 3 metastatic sites (46%), and CA19-9 ≥ 59 × ULN (46%). nab-P + G was superior to G for all efficacy endpoints: median OS was 8.5 vs. 6.7 mo (HR 0.72; 95% CI, 0.617 - 0.835; P = 0.000015); median PFS was 5.5 vs. 3.7 mo (HR 0.69; 95% CI, 0.581 - 0.821; P = 0.000024), and ORR was 23% vs. 7% (P = 1.1 × 10−10) by RECIST v1.0. Metabolic response by PET in 257 patients was 63% for nab-P + G vs 38% for G (P = 0.000051). CA19-9 response (≥ 90% decrease) was 31% for nab-P + G vs. 14% for G (P < 0.0001). Grade ≥ 3 AEs with nab-P + G vs. G included neutropenia (38% vs. 27%), fatigue (17 % vs. 7%), diarrhea (6% vs 1%), and febrile neutropenia (3% vs. 1%). Grade ≥ 3 peripheral neuropathy (PN) occurred in 17% vs. 1% of pts who received nab-P + G vs. G, respectively; for nab-P + G, PN improved to grade ≤ 1 in a median 29 days, and 44% of patients resumed nab-P treatment. The median duration of treatment was 3.9 mo for nab-P + G and 2.8 mo for G. Conclusions: MPACT was a large, international study performed at community and academic centers. nab-P + G was superior to G across all efficacy endpoints, had an acceptable toxicity profile, and is a new standard for the treatment of metastatic PC that could become the backbone for new regimens. Clinical trial information: NCT00844649.
JASPAC 01: Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer.
Authors: Fukutomi Akira , Uesaka Katsuhiko , Boku Narikazu , Kanemoto Hideyuki , Konishi Masaru , Matsumoto Ippei , Kaneoka Yuji , Shimizu Yasuhiro , Nakamori Shoji , Sakamoto Hirohiko , Morinaga Soichiro , Kainuma Osamu , Imai Koji , Sata Naohiro , Hishinuma Shoichi , Nakamura Takayuki , Kanai Michio , Hirano Satoshi , Yoshikawa Yukinobu , Ohashi Yasuo
Published: March 2020

4008

Background: Adjuvant chemotherapy with gemcitabine (G) has been standard treatment for resected pancreatic cancer (PC). In the GEST study, S-1 (S) had shown non-inferiority to G in overall survival (OS) for unresectable PC. The aim of this phase III study is to investigate non-inferiority of S to G on OS as adjuvant chemotherapy for resected PC. Methods: Patients (pts) after macroscopically curative resection of PC with an ECOG PS of 0-1 and adequate organ functions were randomly assigned to G (1000 mg/m2, iv, d1, 8 and 15, q4w, for 6 courses) or S (80/100/120 mg/day based on BSA, po, d1-28, q6w, for 4 courses) with balancing by surgical margins (R), nodal status (N) and institution. Primary endpoint was OS. With 180 pts per arm, the study had 80% power to prove non-inferiority with a margin of hazard ratio (HR) 1.25 on the basis of expected HR 0.87, with 0.05 two-sided alpha. Secondary endpoints were relapse-free survival (RFS), safety, and quality of life (EQ-5D). One interim analysis was planned after 180 deaths. Results: From 4/2007 to 6/2010, 385 pts were enrolled from 33 hospitals in Japan. 378 pts (G/S: 191/187) were included in the full analysis set. Pts characteristics (G/S) were well balanced (PS0: 67%/70%, R0: 86%/88%, N0: 38%/36%). Based on the interim analysis with 205 OS events, IDMC recommended to publish the results. OS at 2-years were 53% for G and 70% for S. HR for S to G was 0.56 (95% CI, 0.42-0.74, p<0.0001 for non-inferiority, p<0.0001 for superiority). On subgroup analysis, HRs for R0/R1, N0/N1 pts were 0.57 (95% CI, 0.42-0.78)/0.53 (0.27-1.05), 0.48 (0.28-0.83)/0.58 (0.41-0.80), respectively. RFS at 2-years were 29% for G and 49% for S. HR of relapse for S to G was 0.56 (95% CI, 0.43-0.71, log-rank p<0.0001). Incidences of grade 3/4 toxicities in G/S were leukopenia 39%/9%, hemoglobin decrease 17%/13%, thrombocytopenia 9%/4%, elevated AST 5%/1%, fatigue 5%/5%, and anorexia 6%/8%. Relative dose intensity of G/S was 84%/97%. EQ-5D QOL score in S was significantly better than that in G (p<0.0001). Conclusions: S-1 adjuvant chemotherapy is shown non-inferior, and furthermore, even superior to GEM. S-1 is considered as the new standard treatment for resected PC pts. Clinical trial information: UMIN000000655.
Vismodegib (V), a hedgehog (HH) pathway inhibitor, combined with FOLFOX for first-line therapy of patients (pts) with advanced gastric and gastroesophageal junction (GEJ) carcinoma: A New York Cancer Consortium led phase II randomized study.
Authors: Cohen Deirdre Jill , Christos Paul J. , Kindler Hedy Lee , Catenacci Daniel Virgil Thomas , Bekaii-Saab Tanios B. , Tahiri Sanaa , Janjigian Yelena Yuriy , Gibson Michael K. , Chan Emily , Rajdev Lakshmi , Urba Susan , Wade James Lloyd , Kozuch Peter , Love Erica , Vandris Katherine , Takebe Naoko , Hochster Howard S. , Sparano Joseph A. ,   New York Cancer Consortium
Published: March 2020

4011

Background: The HH pathway is overexpressed in gastroesophageal (GE) tumors. Pre-clinically, HH inhibitors have demonstrated a reduction in GE tumor growth, cell motility and invasiveness. V, an oral small-molecule antagonist of the Hh pathway, has previously been safely combined with FOLFOX chemotherapy. Methods: Pts with untreated metastatic or locally advanced gastric or GEJ adenocarcinoma were randomized 1:1, stratified by institution and disease status (with or w/o distant mets) to FOLFOX (ox 85 mg/m2, LV 200 mg/m2, 5-FU bolus 400 mg/m2, 5-FU infusion 2400 mg/ m2 over 48 hrs) q14d plus V or placebo (P) (150mg PO daily). Cycle defined as 2 weeks and no crossover allowed at progression. FFPET and blood were collected for biomarker analyses. Response assessed every 8 weeks (RECIST 1.1). Primary endpoint was progression-free survival (PFS), secondary objectives were overall survival (OS), response rate (RR), and toxicity. Results: 124 pts enrolled at 20 sites between 10/09-2/12. 123 pts eligible for analysis (V/P 60/63). Pt characteristics (V/P): median age 58/62; ECOG PS 0: 24 (40%) / 30 (48%); male 39 (65%) / 52 (83%); GEJ 37 (62%) / 39 (61%); diffuse or mixed histology 19 (32%) / 10 (16%), recurrent disease 10(17%) / 16 (25%). Median number of FOLFOX cycles 10/11. Most common Grade ≥3 toxicities: (% pts V/P) neutropenia 50/32 (p=0.07), neuropathy 19/13 (p=0.49), fatigue 15/10 (p=0.50), thrombosis 14/11 (p=0.92), anemia 10/10 (p=0.99), hemorrhage-GI 8/11 (p=0.77), hypokalemia 10/5 (p=0.76), nausea 8/8 (p=0.99). Death on or within 30 days of treatment 6.7%/15.6% (p=0.20). Median PFS in intent to treat population 7.3/8.0 mo (95% CI 4.6-10.1/5.1-11.0; p=0.64) and median OS 11.5/14.9 mo (95% CI 9.6-13.4/11.3-18.4; p=0.23). Overall RR (%) 35/35 (p=0.99). Conclusions: Addition of V to FOLFOX did not improve PFS in an unselected advanced GE carcinoma population. Blood and tissue biomarker analyses are ongoing to determine if there is a subset of patients who may derive benefit from V. Supported by: N01-CM-62204, -62201, -62207, -62206, -62209, -62208 and 2UL1 TR000457-06. Clinical trial information: NCT00982592.
Final analysis of a phase IB/randomized phase II study of gemcitabine (G) plus placebo (P) or vismodegib (V), a hedgehog (Hh) pathway inhibitor, in patients (pts) with metastatic pancreatic cancer (PC): A University of Chicago phase II consortium study.
Authors: Catenacci Daniel Virgil Thomas , Bahary Nathan , Nattam Sreenivasa R. , Marsh Robert de Wilton , Wallace James Alfred , Rajdev Lakshmi , Cohen Deirdre Jill , Sleckman Bethany G. , Lenz Heinz-Josef , Stiff Patrick J. , Thomas Sachdev P. , Xu Peng , Henderson Les , Horiba Margit Naomi , Vannier Michael , Karrison Theodore , Stadler Walter Michael , Kindler Hedy Lee
Published: March 2020

4012

Background: Sonic Hh (SHh), the ligand for the Hh pathway, is over-expressed in >80% of PC. V had activity in preclinical murine PC models leading to increased tumor perfusion, enhanced tumor delivery of G, and an improvement in survival. Methods: We conducted a placebo-controlled, phase IB/randomized phase II trial of GV or GP. Eligible pts, KPS 80-100, had untreated metastatic PC, or had completed adjuvant therapy > 6 months (mo) prior. Primary endpoint: progression-free survival (PFS). Correlatives: serial SHh serum levels; serial perfusion CT imaging. All pts received G 1000mg/m2over 30 minutes, days (D) 1, 8, 15, Q28D. A lead-in phase IB was performed. Pts, stratified by KPS (80 v 90/100), and disease status (newly diagnosed/recurrent), were randomized to V (150 mg PO daily) or P. For pts on P, cross-over was allowed at progression. Assuming a mPFS of 3.5 months for GP and 5.7 months for GV (HR=0.61), a sample size of 106 subjects (53 per group) provided 85% power to detect this difference, using a one-sided test at the 0.10 significance level. Results: No safety issues were identified in 7 pts enrolled in the phase IB study. The phase II study enrolled 106 evaluable pts (V/P 53/53) at 13 sites 2/10-6/12. Pt characteristics: median age 65/64 (range 52-82/39-83); KPS (% pts) 80: 38/30; 90: 26/38; 100: 36/32; newly diagnosed 91%/91%; recurrent: 9%/9%. Grade 3/4 toxicity (V/P, % pts, >5% in either arm): neutropenia 32/28; lymphopenia 4/15; thrombocytopenia 9/11; anemia 9/23; hyponatremia 4/15; fatigue 13/8; hyperglycemia 23/19; elevated ALT 13/9; hyperbilirubinemia 11/6; nausea 11/11. Response (%): CR 0/2, PR 8/11, SD 51/38. mPFS: 4.0/2.5 mo (95% CI: 2.5-5.3/1.9-3.8; HR 0.81 [0.54-1.21], p=0.30). 22 pts (42%) on GP crossed over to GV at progression. mOS: 6.9/6.1 mo (95% CI:5.8-8.0/5.0-8.0, HR 1.04, [0.69-1.58], p=0.84). Updated laboratory/radiological correlatives will be presented. Conclusions: Toxicity between the groups was similar. The addition of V to G in an unselected cohort does not improve response, PFS, or OS in pts with metastatic PC. Funding NCI N01-CM-62201. Clinical trial information: NCT01064622.
Use of pharmacogenomic modeling in pancreatic cancer for prediction of chemotherapy response and resistance.
Authors: Yu Kenneth H. , Sangar Vineet , Ricigliano Mark , Hidalgo Manuel , Abou-Alfa Ghassan K. , Lowery Maeve Aine , Saltz Leonard , Crotty Joseph F. , Gary Kristen , Yin Jing , Choi Eun Yong , O'Reilly Eileen Mary
Published: March 2020

4017

Background: Pancreatic adenocarcinoma (PDAC) is uniformly lethal and is the 4th leading cause of cancer mortality. Despite this, modern cytotoxics (C) can induce tumor responses and extend life. Xenograft models have shown that pharmacogenomic (PGx) modeling of C can predict efficacy. Chemo-sensitivity and gene expression profiling of circulating tumor and invasive cells (CTICs) isolated from peripheral blood may predict tumor response, progression and resistance. Methods: A prospective MSKCC study has completed planned accrual of 50 patients. 10 mL of peripheral blood is collected from patients with unresectable PDAC prior to C and at disease progression. Clinical data is prospectively collected. CTICs are isolated (Vita-Cap, Vitatex Inc.), total RNA is extracted and gene-expression analysis is performed. PGx models for twelve chemotherapy drug combinations used in PDAC were created from the GI50 data obtained from the NCI-60 cell lines (CellPath Therapeutics, Inc., Baltimore, MD). Expression data were normalized through GCRMA then probed to identify expression differences between patients with short v long TTP and within patients at baseline v at time of progression. The analysis was performed at the pathway and individual gene level. Results: CTICs were isolated, and gene expression and chemo-sensitivity patterns were obtained in all 50 patients prior to initiating C and in 20 patients at 1st line disease progression. Preliminary analysis demonstrates clinical benefit for patients treated with C predicted to be effective versus ineffective (TTP 7.3 mo v 3.7 mo, p=0.017, HR 0.30). Changes in chemo-sensitivity patterns were evident at disease progression, reflecting treatment resistance. Pathway analysis revealed that E2F1 and NFκB pathways are associated with prognosis, PLC and RB1 pathways become disrupted with disease progression. Conclusions: Isolation and gene expression profiling of CTICs can be performed reliably in unresectable PDAC. Preliminary analysis suggests that C profiling can predict response. Repeat PGx profiling identifies key pathways associated with treatment resistance. Clinical trial information: NCT01474564.
KRAS mutation status-stratified randomized phase II trial of GEMOX with and without cetuximab in advanced biliary tract cancer (ABTC): The TCOG T1210 trial.
Authors: Chen Li-Tzong , Chen Jen-Shi , Chao Yee , Tsai Chang-Sung , Shan Yan-Shen , Hsu Chiun , Huang Shiu-Feng , Tsou Hsiao-Hui , Lee Kuan-Der , Chiu Chang-Fang , Rau Kun-Ming , Ho Ching-Liang , Yu Ming-Sun ,   Taiwan Cooperative Oncology Group
Published: March 2020

4018

Background: Gemcitabine/platinum combination is considered as globally acceptable standard care in patients with ABTC. Two recently published randomized trials showed adding EGFR antagonist, either erlotinib or cetuximab, does not further improve the clinical outcomes of gemcitabine/oxaliplatin (GEMOX)-treated ABTC patients. However, the impact of KRAS mutation status on the results of both studies was not properly addressed. Methods: A prospective, multicenter randomized, phase II trial to evaluate the therapeutic efficacies of adding cetuximab to GEMOX in patients with ABTC, in which eligible patients were stratified by status of KRAS mutation and ECOG PS, and tumor location then randomized to receive either GEMOX (gemcitabine 800 mg/m2, fixed-rate infusion and oxaliplatin 85 mg/m2, i.v., Q 2 weeks) or GEMOX plus cetuximab (500 mg/m2, i.v., Q 2 weeks, C-GEMOX). The primary endpoint was overall response rate (ORR). As an exploratory trial, 120 (60 per arm) patients was estimated to detect a two-tailed 10% difference in ORR (20% in GEMOX and 30% in C-GEMOX) with a significant level of a=0.2 and b=0.5. Results: Between Nov 2010 and May 2012, a total of 122 patients were accrued. The demography was male: 47.5%, median age: 60 y/o, ECOG PS 0/1: 28.7%/71.3%, IHCC/EHCC/GBC: 71.3%/16.4%/12.3%, KRAS mutation: 36.1%, with locally advanced/metastatic diseases: 32.0%/68.0%, and prior surgical resection: 41.8%. On intent-to-treat analysis, the ORR and DCR in the C-GEMOX (N=62) and GEMOX (N-60) arms was 27.3% vs 15.0% (p=0.1223) and 82.2% vs 60.0% (p=0.0090), respectively (Fisher’s exact test); while the median PFS was 7.1 vs 4.0 months (p= 0.0069) and median OS was 10.3 vs 8.8 months (p=0.4057), respectively (log-rank test). Planned subgroup analysis showed the 43 patients with KRAS mutated tumors benefited more from cetuximab therapy, with a DCR of 78.3% vs 38.1% (p=0.0132), median PFS of 7.0 vs 1.9 months (p=0.0351) and median OS of 10.3 vs 6.6 months (p=0.6924). Conclusions: Adding cetuximab significant improves the DCR and PFS of GEMOX in ABTC patients, notably in subpopulation with KRAS mutated tumors. Larger-scale phase III trial is warranted. Clinical trial information: NCT01267344.
MAGIC trial gene expression profiling study.
Authors: Smyth Elizabeth Catherine , Tan Iain BeeHuat , Cunningham David , Wotherspoon Andrew , Lin Suling Joyce , Okines Alicia Frances Clare , Langley Ruth E. , Nankivell Matthew , Stenning Sally P. , Tan Patrick
Published: March 2020

4020

Background: The MRC MAGIC trial established perioperative epirubicin, cisplatin and 5FU (ECF) chemotherapy as a standard of care for patients (pts) with operable oesophagogastric (OG) cancer (Cunningham NEJM 2006). We performed transcriptomic profiling of archival MAGIC tissue to evaluate an existing intrinsic gastric cancer (GC) gene signature, to describe expression patterns of biologically informative genes and to identify prognostic or predictive markers. Methods: RNA was extracted from formalin fixed paraffin embedded (FFPE) resections and analysed with the NanoString nCounter system. Our panel comprised 151 genes including intrinsic GC (G-INT and G-DIFF) signature genes (Tan Gastroenterology 2011), and genes amplified/deleted in GC including the therapeutic targets FGFR2, EGFR, ERBB2 and c-MET (Deng Gut 2012). Data was preprocessed using nsolver analysis software with 2-step normalisation and log2 transformed. G-INT and G-DIFF subtype classification used the nearest template prediction algorithm; these were then correlated with pt characteristics and survival. The overexpression threshold was defined as deviation above the normal quantile-quantile plot. Results: Sufficient RNA for analysis was available for 209 resected pts. A pilot study (n=23) confirmed RNA quality and correlation between NanoString and Affymetrix results. RNA was more often available for pts with GC (p<0.001) and pts in the surgery alone arm (p=0.049). 70% of pts were classified into G-INT or G-DIFF intrinsic signature subtype (false discovery rate (FDR) <0.05); 61 (30%) were ambiguous. Predominantly mutually exclusive overexpression of receptor tyrosine kinase (RTK) targets EGFR, ERBB2, FGFR, and c-MET was seen in 5%, 12%, 9% and 6% of pts respectively. Conclusions: Although bias may exist in tissue availability for chemosensitive pts, transcriptomic profiling of archival FFPE from this mature phase 3 study provides powerful insight into the molecular heterogeneity of OG cancer. 70% of evaluable MAGIC pts were classified unambiguously into intrinsic GC subtypes. Mutually exclusive overexpression of targetable RTKs supports a personalized approach in OG cancer evaluating targeted drugs in relevant biological subgroups. Survival analyses are ongoing.
Randomized phase II trial of extended versus standard neoadjuvant therapy for esophageal cancer, NCCTG (Alliance) trial N0849.
Authors: Alberts Steven R. , Soori Gamini S. , Shi Qian , Wigle Dennis A. , Sticca Robert P. , Miller Robert Clell , Leenstra James L. , Peller Patrick J. , Wu Tsung-Teh , Yoon Harry H. , Drevyanko Timothy F. , Ko Stephen , Mattar Bassam Ibrahim , Nikcevich Daniel A. , Behrens Robert J. , Khalil Maged F. , Kim George P.
Published: March 2020

4026

Background: Patients (pts) with locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma commonly receive neoadjuvant chemoradiotherapy (chemo-RT). Despite this approach the rate of recurrence remains high. Given the difficulties of postoperative therapy, the efficacy of extended neoadjuvant therapy was assessed. Methods: Eligibility criteria included T3-4,N0 – Tany,N(+) disease amenable to radiation and surgery. Pts were randomized to either arm A (docetaxel 60 mg/m2 day 1 , oxaliplatin [Oxal] 85 mg/m2 day 1, and capecitabine 1250 mg/m2/day days 1-14 x 2 cycles [DOC] followed by 5-FU 180 mg/m2/day continuous IV through radiation + Oxal 85 mg/m2 days 1,15,29 + 50.4 Gy radiation (chemo-RT)) or arm B (chemo-RT alone). Randomization was stratified by ECOG PS (0/1 vs 2) and stage (II vs III/IVA). Primary endpoint was pathologic complete response (PCR) rate, defined as no gross or microscopic tumor identified in the surgical specimen. Interim analysis assessed efficacy and futility of the experimental intervention. Wilcoxon rank sum and Fisher’s exact tests were used to compare clinical/pathologic factors between arms. Results: Baseline and stratification factors were well balanced between arms. Of 42 pts included in the interim analysis (86% male; age [median 63, range 38-88], 100% PS 0/1; 71% stage III; 55% esophagus, 40% GEJ; 36% measurable disease), 4 and 1 pts in arms A and B, respectively, did not have surgery due to death (A, 2), progressive disease (A, 1), alternative treatment (A, 1) or adverse event (B, 1). Among 21 arm A pts, 21, 20, and 19 pts started 1st cycle of DOC, 2nd cycle of DOC and chemo-RT, respectively. All arm B pts received chemo-RT. 33% (7/21) of arm A and 48% (10/21) of arm B pts achieved PCR (p=0.53). Among pts undergoing surgery, 94% (16/17) and 100% (20/20) of arm A and B pts had complete resection (p=0.46). 38% and 24% of arm A and B pts experienced at least one grade 4+ adverse event at least possibly related to treatment (p=0.51). Conclusions: Extended neoadjuvant therapy in pts with locally advanced esophageal or GEJ adenocarcinoma failed to improve the PCR rate. Follow-up in regard to survival and rate of recurrence is ongoing. Clinical trial information: NCT00938470.
The impact of diabetes on HCC.
Authors: Graef Suzanne , Berhane Sarah , Teng Mabel Joey , Skowronska Anna , Johnson Philip James
Published: March 2020

4029

Background: The incidence of hepatocellular carcinoma (HCC) in the UK has increased by 40% over the last 20 years, with a corresponding increase in mortality rate. The rising incidence of obesity and type II diabetes are believed to be contributing factors due to the association with non-alcoholic fatty liver and steatohepatitis. We aimed to examine if diabetes was as an independent risk factor for the development of HCC and to assess the impact of diabetes on overall survival (OS). Methods: Data from 724 patients with HCC and a control group comprising 340 patients with chronic liver disease were collected prospectively between 2007 and 2012. The odds ratio (OR) for HCC in diabetic versus non-diabetic patients was calculated. Univariate and multivariate analysis was performed using logistic regression. Cox proportional hazards analysis was used to estimate hazard ratio (HR) for death for HCC patients, with and without diabetes and for the impact of variation in diabetic treatments. Results: The prevalence of diabetes was 39% within the HCC population and 10.3% within the chronic liver disease group. Univariate analysis demonstrated increased risk of HCC associated with age, sex, diabetes, haemochromatosis, cirrhosis, alcohol abuse and Child’s score. In patients with diabetes OR for HCC was 5.74 (CI 3.9-8.3; p<0.001). Age, sex, cirrhosis, Child’s score, diabetes and diabetes treatment with insulin, retained significance as independent risk factors in multivariate analysis. There was no survival difference for HCC patients with and without diabetes. In diabetic patients with HCC, treatment of diabetes with metformin, compared against other diabetic treatment options, was associated with a significantly longer OS (31 versus 24 months, p = 0.016; HR 0.74, p = 0.027). Conclusions: This study has demonstrated that diabetes is an independent risk factor for the development of HCC in a high risk population and that treatment with insulin appears to confer further independent risk. Diabetes has no effect on survival following the development of HCC but treatment of diabetes with metformin is associated with prolonged survival. In considering the optimal treatment for diabetes in chronic liver disease the beneficial effects of metformin on OS, if HCC develops, should be taken into account.
DOCOX: A phase II trial with docetaxel and oxaliplatin as a second-line systemic therapy for patients with advanced and/or metastatic adenocarcinoma of the pancreas.
Authors: Ettrich Thomas Jens , von Wichert Goetz , Gress Thomas M. , Michl Patrick , Geissler Michael , Hebart Holger Frithjof , Berger Andreas W. , Porzner Marc , Danner Bettina , Muche Rainer , Seufferlein Thomas
Published: March 2020

4034

Background: In Europe and the USA, pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of cancer-related death. For patients with metastatic disease, palliative cytostatic systemic treatment is the only option. There is no established standard for 2nd-line treatment. Fluoropyrimidines either alone or in combination with Oxaliplatin or other chemotherapeutic agents are increasingly used. There are interesting data regarding the combination of Gemcitabine with Oxaliplatin or Docetaxel with respect to progression free survival (PFS) and tumor response in 1st-line. For the first time, the DocOx-trial investigates the combination of Oxaliplatin with Docetaxel as 2nd-line treatment after progression under palliative first-line systemic treatment with Gemcitabine. Methods: Prospective, single arm, non-randomized, multicenter, Simon´s two stage phase II trial using Docetaxel (75 mg/m2, 60 min, d 1) plus Oxaliplatin (80 mg/m2, 120 min, d 2, qd 22). Duration of the trial is scheduled up to 8 cycles. Primary endpoint: tumor response (RR) according to RECIST 1.0. Secondary endpoints: PFS, OS, safety/toxicity, QoL/clinical benefit. Results: Here we present the data on response rate (RR), median progression free survival (mPFS) and median overall survival (mOS) as of February 4th, 2013. Data represents the Intention to treat-analysis of the 44 patients included between 2009 and 2012. 5 patients did not obtain any treatment. RR was 16% (7 partial remissions, no complete remission) with a disease control rate (DCR) of 48% after the first two treatment cycles. Median PFS was 7 weeks ( 95%-CI: 6-16 w.) and median OS after start of 2nd-line therapy was 36 weeks ( 95%-CI: 19-55 w.). Conclusions: In this single-arm 2nd-line trial for the treatment of PDAC, the combination of Doxcetaxel and Oxaliplatin shows very promising results compared to other 2nd-line-protocols such as OFF. Some patients seem to benefit particularly as indicated by long periods of treatment in this setting. Even after 8 cycles of treatment with DocOx, partial response was observed in 2 patients and stable disease in another 6 patients corresponding a disease control rate of 18%. Clinical trial information: NCT00690300.
A pilot phase II multicenter study of nab-paclitaxel (Nab-P) and gemcitabine (G) as preoperative therapy for potentially resectable pancreatic cancer (PC).
Authors: MacKenzie Shawn , Zeh Herbert , McCahill Laurence E. , Sielaff Timothy D. , Bahary Nathan , Gribbin Thomas Edward , Seng John E. , Leach Joseph W. , Harmon Jocelyn , Demeure Michael J. , Von Hoff Daniel D. , Moser A Jim , Ramanathan Ramesh K. ,   PCRT
Published: March 2020

4038

Background: Nab-P plus G is a new option for advanced PC. This combination was evaluated as a preoperative regimen for potentially resectable PC. Methods: Patients (pts, n=25) with resectable PC (NCCN criteria) were treated with 3 cycles of Nab-P (125mg/m2) & G (1000mg/m2) on day 1, 8, and 15, followed by surgical resection. The chosen endpoint was Grade III/IV histological changes (Arch Surg.127:1335-39:1992) in > 30% of resected tumor specimens. Results: Accrual is complete with 25 pts (median age 65, 10 F:15 M), 14/25 completed 3 cycles of treatment. Early drug discontinuation or drug interruption prior to the completion of 3 cycles occurred in 11 pts due to azotemia, cholangitis, pneumonia, catheter infection and pt decision. One pt had a fatal (grade 5) non-neutropenic aspergillus pneumonia. There was one episode of neutropenic fever (4%), and 3 episodes of cholangitis (12%) due to biliary stent malfunction. Other adverse events (grade 3/4) include neutropenia 64%, anemia 20%, dehydration 12%, nausea 12% and thrombocytopenia 12%. Dose reductions due to AEs were required in 5 pts, (3-neutropenia, 2-rash). Surgical resection was successful in 20/25 pts: 12- Pancreaticoduodenectomy, 8- Distal Pancreatectomy, 19/20 pts underwent an R0 resection. Surgical resection was not done in 5/25 pts due to: pre-operatively identified metastatic disease (2), blood vessel involvement at surgery (1), pt declined (1) and a pre-operative death (1).Post-operative tumor staging identified a complete response (n=1); stage IA (n=1); stage IIA (n=6); and stage IIB (n=12). Radiological partial response (PR) was documented in 4 pts prior to surgery. CA19-9 levels decreased from baseline by > 50% in 60% (n=15) of pts and by > 90% in 16% (n=4). Post-operative > 90% histological tumor response (Grade 3/4) was seen in 6 of 20 (30%) resected specimens. Conclusions: Preoperative therapy with Nab-P plus G is feasible with evidence of activity by radiological (PR in 16%), CA19-9 (decrease > 50% in 60% of pts) and pathological down staging (Grade 3/4 in 30% in resected tumor specimens). A larger study is warranted. Supported by Abraxis/Celgene Pharmaceuticals and the TGen foundation. Clinical trial information: NCT01298011.
Whole-transcriptome paired-end sequencing and the pancreatic cancer genetic landscape.
Authors: Macchini Marina , Astolfi Annalisa , Indio Valentina , Vecchiarelli Silvia , Grassi Elisa , Serra Carla , Casadei Riccardo , Santini Donatella , D'Ambra Marielda , Ricci Claudio , Minni Francesco , Biasco Guido , Di Marco Mariacristina
Published: March 2020

4048

Background: A deeper knowledge of the pancreatic cancer (PDAC) biology is needed to improve the prognosis of the disease. Methods: 17 PDAC samples were collected by ultrasound-guided biopsy used for DNA and RNA extraction. 14 samples were analyzed by high resolution copy number analysis (CNA) on Affymetrix SNP array 6.0 and with segmentation algorithm against a reference of 270 Ceu HapMap individuals (Partek Genomic Suite). 17 samples were analyzed by whole transcriptome massively parallel sequencing, performed at 75x2 bp on a HiScanSQ Illumina platform. An average of 7, 3x107 reads per sample were generated, with a mean read depth of 50X. Single nucleotide variants (SNVs) were detected with SNVMix2 and compared with genetic variation databases (dbSNP, 1000genomes, Cosmic). Non-synonimous SNVs were analyzed with the predictors SNPs and GO and PROVEAN. Results: CNA results in 9/14 samples exhibited both macroscopic and cryptic cytogenetic alterations, with a mean of 10 CNA per patient. Most frequent gains were observed in 18q11.2 involving GATA6 (3/14) and 19q13 targeting AKT2 (3/14) while hotspot deletions were found on 18q21 (7/14), 17p13 (6/14), 9p21.3 (6/14), 15q (5/14) and 1q35 (4/14). RNAseq showed that samples exhibited a mean of 145 (range: 61-240) non-synonimous SNVs, of which 16 on average are potentially disease-related. Merging copy number and RNAseq data we highlighted the major oncogenic hits of PDAC, confirming the prevalence (14/17) of KRAS mutations, in one case also NRAS (G13D), and the three oncosuppressor CDKN2A (mutated in 3 cases and deleted in 6 cases, in hetero- or homozygosity), SMAD4 (altered by point mutation or gene deletion in 7/14), and TP53 (lost in 6/14 and mutated in 5/17). The signaling pathways affected were: KRAS/MAPK, TGFbeta and integrin signaling, proliferation and apoptosis, DNA damage response, and epithelial to mesenchymal transition. Moreover we found new oncogenic alterations, such as HMGCR, that displayed mutations in 17% of the analyzed patients (3/17). Conclusions: NGS combined with high resolution cytogenetic analysis can improve the understanding of pancreatic carcinogenesis.
Clinical characterization of hypoxia in pancreatic ductal adenocarcinoma (PDAC) by 18F-FAZA PET and pimonidazole.
Authors: Metran Nascente Cristiane , Dhani Neesha C. , Vines Douglass , Yeung Ivan , Metser Ur , Serra Stefano , Milosevic Michael , Gallinger Steven , Hedley David W.
Published: March 2020

4049

Background: We previously demonstrated correlation between hypoxia and aggressive tumor biology in orthotopic, patient-derived pancreatic xenografts (Chang et al. Cancer Res 2011). With the development of hypoxia-directed therapies, there is a need to understand the range and relevance of hypoxia in PDAC patients. We therefore launched two complementary clinical trials using 2-nitroimidazole-based hypoxia probes. Methods: PIMO-PANC involves pre-operative administration of pimonidazole to patients (pts) undergoing PDAC resection. Hypoxic percent (HP) of tumors is determined by semi-automated image analysis (on Aperio’s Genie) of multiple histological sections stained for pimonidazole by immunohistochemistry (IHC). FAZA-PANC uses the positron emission tomography (PET) tracer fluoroazomycin arabinoside (18F-FAZA) to evaluate hypoxia by functional imaging. 2 hours post-injection of (5.2 MBq/kg) 18F-FAZA, static scans are acquired followed by computed tomography for anatomic registration. Skeletal muscle is a non-hypoxic reference tissue to define standardized uptake values (SUV), tumor to muscle uptake ratios (T/M’s) and a threshold for hypoxia. Results: PIMO-PANC has enrolled 29 pts and FAZA-PANC 16. IHC analysis of the first 10 pt tumors demonstrates considerable intra- and inter-tumoral heterogeneity of hypoxia (HP: 1 to 26% across pt tumors); minimal hypoxia (< 5%) was observed in 3 pts. 18F-FAZA-PET in the first 11 pts demonstrates SUVmax from 1.02 to 1.83, median T/M's from 0.84 to 1.31. A threshold of 1.27 SUVmax defines HP of 0 to 60% with minimal hypoxia (<10%) in 5 pts. Conclusions: There is significant heterogeneity of hypoxia across the spectrum of clinical PDAC (local to metastatic disease) using the 2-nitroimidazole hypoxia probes pimonidazole and 18F-FAZA. Given the intra-tumoral heterogeneity of hypoxia by histopathology, functional imaging is the preferred method to assess hypoxia in PDAC patients. Importantly, both methods identified a group of PDAC tumors with low levels of hypoxia. This is relevant to the on-going development of hypoxia-targeting strategies. Accrual to PIMO-PANC is on-going and will address the prognostic relevance of hypoxia in PDAC. Clinical trial information: NCT01542177 and NCT01248637.
Significance of baseline quality of life scores in predicting clinical outcomes in an international phase III trial of advanced pancreatic cancer: NCIC CTG PA.3.
Authors: Vickers Michael M. , Tu Dongsheng , Lee Chee , Wheatley-Price Paul , Parulekar Wendy , Brundage Michael Donald , Moore Malcolm J. , Au Heather-Jane , O'Callaghan Christopher J. , Jonker Derek J. , Ringash Jolie , Goldstein David
Published: March 2020

4053

Background: There is insufficient information regarding the prognostic significance of baseline Quality of life (QoL) scores on overall survival (OS) and adverse events (AEs) in advanced pancreatic cancer. Methods: QoL was assessed prospectively using the EORTC QLQ-C30 and AEs were graded using the NCI Common Toxicity Criteria version 2.0 as part of the PA.3 trial of gemcitabine + erlotinib (G+E) vs. gemcitabine + placebo (G+P). Relevant clinical variables, ECOG performance status (PS), and QoL scores at baseline were analyzed by Cox stepwise regression to determine predictors of OS and AEs. QoL scores were transformed by square root. Results: 222 of 285 patients (pts) (78%) treated with G+E and 220 of 284 pts (77%) treated with G+P completed baseline QoL assessments. In a multivariate Cox analysis (MVA) combining all pts, better QoL physical function (PF) score independently and incrementally predicted longer OS (HR 0.91; CI: 0.83-1.00), as did non-white race (HR 0.62; CI: 0.42-0.91), PS 0-1 (vs. PS 2 - HR 0.64; CI: 0.49-0.84), locally advanced pancreatic cancer (LAPC) (vs. metastatic - HR 0.54; CI: 0.42-0.69) and G+E (vs. G+P - HR 0.79; CI: 0.64-0.98). More financial difficulty (HR 0.92; CI: 0.87-0.98) and PS 0-1 (HR: 0.36; CI: 0.17-0.77) predicted a lower risk of grade 3 or higher AEs. In a MVA of pts treated with G+E, pain intensity <20 (vs. ≥ 20 - HR 0.68; CI:0.52-0.88) and LAPC (HR 0.67; CI: 0.48-0.91) were associated with longer OS, while better QoL cognitive (HR 0.71; CI: 0.50-1.00), worse constipation (HR 0.89; CI: 0.81-0.98) and worse financial scores (HR 0.86; CI: 0.78-0.94), better dyspnea score (HR 0.82; CI: 0.71-0.93) and PS 0-1 (HR 0.21; CI: 0.05-0.78) predicted for lower risk of AEs. In a MVA of pts treated with G+P, better global QoL score (HR 0.91; CI:0.85-0.98) and LAPC (HR 0.57; CI: 0.40-0.82) were predictors of longer OS while no variables predicted grade 3 or higher AEs. Conclusions: In addition to clinical variables (including physician assessed PS), patient reported QoL scores added incremental predictive information regarding survival and adverse events for advanced pancreatic cancer patients treated with systemic chemotherapy.
Randomized, open-label, phase II trial of gemcitabine with or without bavituximab in patients with nonresectable stage IV pancreatic adenocarcinoma.
Authors: Pandya Shuchi Sumant , Wong Lucas , Bullock Andrea J. , Grabelsky Stephen A. , Shum Merrill Kingman , Shan Joseph , Menander Kerstin B. , Reid Tony R.
Published: March 2020

4054

Background: Despite advances in the treatment of metastatic pancreatic cancer (PC), there is critical need to develop novel therapies.Median survival with combination chemotherapy is limited to less than one year and only the optimally conditioned patients can tolerate these therapies. Bavituximab (B) is a monoclonal antibody (mAB) directed againstphosphatidylserine (PS) that causes vascular shutdown and reactivation of the innate and adaptive immunity in animal models. Preclinical data in mouse PC models indicate that gemcitabine (G) increases PS exposure and the addition of a mAb targeting PS reduces tumor burden, visible liver metastases, microvessel density, and increases tumor macrophage infiltration compared to G alone (Beck et al. 2006). The purpose of this trial is to evaluate and compare the efficacy and safety of the combination of G+B vs. G alone as first line therapy in pts. with nonresectable Stage IV PC. Methods: Seventy patients were randomized (1:1) to receive G 1000 mg/m2 on days 1, 8, and 15 every 28Edays with or without weekly B 3mg/kg IV until disease progression or unacceptable toxicities. Key eligibility criteria were Stage IV PC, ECOG ≤2, measurable disease, age≥18 years, total bilirubin ≤1.5xULN, and adequate renal, hematologic, and hepatic function. The primary efficacy endpoint was overall survival (OS) and secondary endpoints included overall response rate (ORR) and progression free survival (PFS). Results: Of the 70 (G/G+B 34/36) patients randomized, 67 (G/G+B 33/34) received study treatment and 63 (G/G+B 31/32) were evaluable. No significant difference was seen in age, gender, race or ECOG. At analysis 87% deaths had been reported in G and 72% in G+B group. Median OS estimate is 5.2 months for G and 5.6 months for G+B. No difference between groups was observed in PFS (median 3.9 months for G and 3.7 months for G+B). ORR was 13% for G and 28% for G+B. Most AEs were grade 1-2 and typical of exposure to G. Conclusions: In this patient population with extensive disease burdens and limited treatment options, G+B was well tolerated and demonstrated moderate activity in tumor response and survival. Clinical trial information: NCT01272791.
Willingness of patients with pancreatic cancer to participate in clinical trials.
Authors: Cinar Pelin , Talley Anitra W. , Hwang Jimmy , Dohan Daniel Paul , Tempero Margaret A.
Published: March 2020

4055

Background: Recruitment of oncology patients into clinical trials continues to be a challenge as <5% of patients are accrued. Low accrual rates may be due to reduced awareness of trial availability and eligibility by physicians/patients. Our objective was to study the attitudes of patients with pancreatic cancer (PC) regarding clinical trial participation and to identify possible barriers to recruitment. Methods: In this cross-sectional study, we collaborated with Pancreatic Cancer Action Network (PanCAN) and invited patients with PC or their caregivers to complete a survey. The survey that was developed consisted of 22 questions and inquired about patients’ previous clinical trial enrollment experiences and their views on participation. The surveys were collected over a 6-month period via the PanCAN website and regional meetings. Comparison analyses between groups were done by Chi-square and Fisher’s test using STATA software. Results: Of the390 surveys received, 149 were included in the final analyses. 30% of the patients were offered to participate in a trial by their physicians. When asked to participate, 62% of the patients agreed. Of the patients who were not enrolled in a clinical trial, 61% were offered to participate in a trial but did not agree. This suggests that these patients were eligible to participate but declined. Conclusions: Majority of the patients with pancreatic cancer were not offered to participate in clinical trials by their physicians but would have agreed if asked. While low clinical trial recruitment rates for PC may be multifactorial, further research may focus on the important role of physicians in clinical trial recruitment efforts. [Table: see text]
A randomized phase II trial of adjuvant chemotherapy with S-1 versus S-1 and gemcitabine (GS) versus gemcitabine alone (GEM) in patients with resected pancreatic cancer (CAP-002 study).
Authors: Yoshitomi Hideyuki , Shimizu Hiroaki , Yoshidome Hiroyuki , Ohtsuka Masayuki , Kato Atsushi , Furukawa Katsunori , Takayashiki Tsukasa , Kuboki Satoshi , Okamura Daiki , Suzuki Daisuke , Nakajima Masayuki , Aida Toshiaki , Miyazaki Masaru ,   Chiba Study Group of Adjuvant Chemotherapy for Pancreatic Cancer (CAP)
Published: March 2020

4056

Background: Although the adjuvant therapy using GEM is now the standard therapy for patients with resected pancreatic cancer (PC), the prognosis still remains poor. Resent study demonstrated the non-inferiority of S-1 and superiority of GS to GEM with respect to progression free survival in patients with unresectable pancreatic cancer. Methods: Patients with invasive ductal PC who underwent radical surgery were enrolled. After stratification for R0/1, stage and institution, patients were randomized to receive GEM (GEM 1g/ m2, iv, d1, 8, and 15, q4w X12), S-1 (80/100/120mg/day based on BSA, po, d1-14, q3w X 16) or GS (S-1 60/80/100mg/day based on BSA po, d1-14 plus GEM 1g/ m2, iv, d8, 15, q3w X 16) within 8weeks after operation. Eligibility included histological residual tumor (R) 0 or 1, and no previous chemo- or/and radiation therapy. Primary endpoint was 2y disease free survival (DFS) rate and secondary endpoints included overall survival (OS), and safety. Results: Between January 2007 and October 2010, 96 patients were randomized into the three arms of the trial (32 pts to each group). Patients’ characteristics were well balanced (GEM/S-1/GS) with regard to age (66/67/66y), tumor location (head 66/69/75%), tumor status (T3+4 88/78/91%), and nodal status (positive 75/69/75%). Until November 2012, 74 events (77%) have occurred for DFS. Two year DFS rate was 24.2%, 28.1% and 34.4% in GEM, S-1 and GS, respectively and there was no significant difference between groups. The median OS was 21m in GEM, 26m in S-1 and 27.9m in GS (Log rank test: N.S.). Grade 3/4 toxicities in GEM/S-1/GS were hematological 63/10/74% and non-hematological 17/10/23%, respectively. No treatment related death was observed during the study. Conclusions: S-1 and GS provided similar efficacy to GEM as the adjuvant chemotherapy for resected PC. According to the results, S-1 and GS is the adequate combination for phase III trial to examine the efficacy of adjuvant chemotherapy for PC. Clinical trial information: UMIN000002000.