bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of life study in patients with unresectable locally advanced or metastatic pancreatic cancer treated with gemcitabine in combination with nab-paclitaxel versus gemcitabine alone:ax-panc-sy001: A phase II randomized study.
Authors: Yalcin Suayib , Dane Faysal , Oksuzoglu Berna , Yildirim Nuriye , Isikdogan Abdurrahman , Ozkan Metin , Demirag Guzin , Coskun Hasan Senol , Karabulut Bulent , Evrensel Turkkan , Ustaoglu Mehmet Ali , Ozdemir Feyyaz , Turna Hande , Yavuzsen Tugba , Aykan Faruk , Sevinc Alper , Akbulut Hakan , Yuce Deniz , Hayran Mutlu , Kilickap Saadettin ,   Gastrointestinal Cancers Study Group
Published: January 2019

346 Background: Although clinical efficacy of gemcitabine in combination with nabpaclitaxel has been shown to be superior to single agent gemcitabine in a randomize phase 3 trial, data are lacking on the quality of life of this combination regimen as first-line therapy in patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma. Methods: We randomly assigned 125 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 to receive gemcitabine, 1000 mg/m2 plus nabpaclitaxel 125 mg/m2 or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Treatment continued until disease progression or unacceptable toxicity. The primary end point was 3-months deterioration-free rate (percentage of patients free from definitive deterioration) and quality of life of patients. Results: The median overall survival was 9.92 months in the gemcitabine plus nabpaclitaxel group as compared with 5.95 months in the gemcitabine group (hazard ratio for death, 0.642, 95% confidence interval, 0.422 to 0.866; p < 0.038). Median progression-free survival was 6.28 months in the combination group and 3.22 months in the gemcitabine group (hazard ratio for disease progression, 0.582; 95% CI, 0.391 to 0.866; p < 0.008). The objective response rate was 37.1% in the combination group versus 23.7% in the gemcitabine group (p < 0.009). Median time to deterioration was 3.68 months in the gemcitabine arm versus 5.36 months in the combination arm. More data on quality of life will be presented. Conclusions: As compared with gemcitabine, gemcitabine plus nabpaclitaxel was associated with an overall and progressive free survival advantage, with increased response rate, without increasing toxicity and deterioration of quality of life. Gemcitabine and nabpaclitaxel combination regimen with this form is a preferable option for the treatment of patients with advanced pancreatic cancer Clinical trial information: EudraCT: 2013-004180-32.
Efficacy of nab-paclitaxel plus gemcitabine (AG) vs. FOLFIRINOX as first line chemotherapy for metastatic pancreatic cancer (mPC): Real world experiences.
Authors: Hwang Inhwang , Kang Jihoon , Yoo Changhoon , Kim Kyu-Pyo , Jeong Jae Ho , Chang Heung-Moon , Ryoo Baek-Yeol 
Published: January 2019

354 Background: AG and FOLFIRINOX have been established as standard first-line treatment in mPC patients based on the improved efficacy compared to gemcitabine monotherapy. Because there was no head-to-head comparison between these regimens, however, there is lack of data which regimen is preferable in patients with mPC. Therefore, we performed retrospective analysis comparing the efficacy of AG and FOLFIRINOX in daily practice setting. Methods: We analyzed a total of 308 patients with confirmed mPC who received AG (n = 149) or FOLFIRINOX (n = 159) as first-line treatment between 2013 and 2016 at Asan Medical Center, Seoul, Korea. Primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and overall response rates (ORR). Results: Median age was slightly older in AG group than FOLFIRINOX group (62 vs. 60 years, p = 0.02). Except this, there was no significant difference between the two groups in terms of baseline characteristics including sex (male, AG/FOLFIRNOX): 56%/67%, ECOG performance status (0-1): 97%/99%, pancreatic head location: 32%/40%, and baseline CA19-9 level ( > UNL): 77%/82%. ORR (28% vs. 31%) and disease control rate (74% vs. 74%) did not differ between two groups (p = 0.45, and p = 0.96, respectively). Although there was no significant difference in PFS between the two groups (AG: median 6.8 months [95% CI: 5.8-7.8] vs. FOLFIRINOX: 5.1 months [95% CI: 4.2-5.9]; p = 0.15), OS was significantly better in AG group compared to FOLFIRINOX group (median 12.3 months [95% CI: 11.0-13.7] vs. 9.7 months [95% CI, 8.1-11.4]; p = 0.001). Among the patients who showed progression, 81% (180/223) received second-line chemotherapy and there was no difference between the two groups (AG vs. FOLFIRINOX: 76% vs. 85%, p = 0.09). 5-FU monotherapy or combination with oxaliplatin were given in 97% (73/75) of patients in AG group and gemcitabine-based regimens (including 2 cases of AG) were given in 97% (102/105) of patients in FOLFIRINOX group. Conclusions: Both AG and FOLFIRINOX are feasible and active as first-line treatment for patients with mPC. In daily practice setting, AG showed comparable efficacy outcomes with FOLFIRINOX.
Deterioration of liver function after transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): An exploratory analysis of OPTIMIS—An international observational study assessing the use of sorafenib after TACE.
Authors: Kudo Masatoshi , Raoul Jean-Luc , Lee Han Chu , Cheng Ann-Lii , Nakajima Keiko , Peck-Radosavljevic Markus 
Published: January 2019

368 Background: TACE is commonly used for patients (pts) with unresectable HCC, and appropriate pt selection is important to obtain optimal outcomes. However, there is no globally accepted consensus on unsuitability and refractoriness to TACE. Retrospective studies suggest that continuing TACE after refractoriness or failure is harmful and may cause pts to become ineligible for further treatments because of liver function deterioration. This exploratory analysis of OPTIMIS evaluated the real-world incidence of liver function deterioration by baseline liver characteristics after first TACE. Methods: OPTIMIS enrolled 1670 pts with HCC for whom a decision to treat with TACE was made at the time of study entry. Liver function deterioration was defined as worsening of CTCAE grade compared with baseline for any of these parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, albumin, and prothrombin international normalized ratio (INR). All analyses are descriptive. Results: A total of 977 pts received TACE. The incidence of liver deterioration was higher in pts with BCLC stage C vs stage B (52% vs 44%, respectively), in pts exceeding the up-to-7 criteria compared with those within (49% vs 43%, respectively), and in those deemed unsuitable for TACE at baseline versus those deemed eligible (53% vs 44%, respectively) (Table). Conclusions: Deterioration of liver function parameters was observed after TACE in pts with HCC in the real-world setting. Therefore, appropriate pt selection for TACE and preserving liver function are important to optimize the benefit of TACE and subsequent treatments. Clinical trial information: NCT01933945. [Table: see text]
Overall survival of PEGylated human IL-10 (AM0010) with 5-FU/LV and oxaliplatin (FOLFOX) in metastatic pancreatic adenocarcinoma (PDAC).
Authors: Hecht J. Randolph , Naing Aung , Falchook Gerald Steven , Patel Manish R. , Infante Jeffrey R. , Aljumaily Raid , Wong Deborah Jean Lee , Autio Karen A. , Wainberg Zev A. , Javle Milind M. , Bendell Johanna C. , Pant Shubham , Hung Annie , Van Vlasselaer Peter , Oft Martin , Papadopoulos Kyriakos P. 
Published: January 2019

374 Background: The therapeutic options for 2nd line therapy PDAC remain unsatisfying with 5-FU/LV plus oxaliplatin or nal-irinotecan resulting in a mOS of 5-6 mo. PDAC has been largely refractory to immune-oncology approaches and CD8 T cells are rare in most PDAC. AM0010 stimulates survival, expansion and cytotoxicity of intratumoral CD8+ T cells. Immune activation, durable stable disease and a 1yr survival of 22.5% was seen in salvage PDAC patients (pts) receiving AM0010 alone. AM0010 has synergistic anti-tumor activity with 5-FU/LV or oxaliplatin in preclinical models. Here we report on the safety, efficacy and overall survival of AM0010 + FOLFOX as 2nd and later line treatment in PDAC. Methods: PDAC progressing on a median of 2 prior therapies (range 1-5) were treated with AM0010 (5ug/kg SQ, qd) + FOLFOX (n = 21). The safety population (n = 25) included also 4 pts with prior oxaliplatin / 5-FU. The survival population included patients without prior platinum containing regimen. Tumor responses were assessed with irRC. Biomarkers evaluated the activation and clonality of peripheral T cells. Archival tumor tissues were evaluated for tumor infiltration by CD8 T cells, by whole exome sequencing and mRNA analysis. Results: AM0010 + FOLFOX, was generally well tolerated. G3/4 TrAEs included thrombocytopenia (52%), anemia (44%), neutropenia (36%) and fatigue (12%). Most cytopenias had a short duration, reaching retreatment criteria within 2-5 days after dose interruption. Dosing AM0010 for 5 days followed by a 2 days dose holiday avoided G3/4 cytopenias. As of 08/11/2017, 2 patients have remained on treatment for > 1 year. Of 19 evaluable pts, 2 had an irCR, 1 had irPR with 100% reduction in tumor burden, ORR is 15.8%, DCR is 78.9%. With median follow-up of 19.2 months (range 13.4-24.1), mPFS was 3.5 mo, mOS was 10.2 mo and 1-year survival was 43%. Transcriptional profiling and CD8 T cells in the archival tumor tissue may identify patients with longer OS. Conclusions: AM0010 in combination with FOLFOX is well tolerated in patients with metastatic PDAC. Immune activation, mOS and 1 year survival are encouraging in this advanced PDAC population. This regimen is currently being studied in a phase 3 trial Clinical trial information: NCT02009449.
Phase I study of defactinib combined with pembrolizumab and gemcitabine in patients with advanced cancer.
Authors: Wang-Gillam Andrea , Lockhart A. Craig , Tan Benjamin R. , Suresh Rama , Lim Kian-Huat , Ratner Lee , Morton Ashley , Huffman Jess , Marquez Samantha , Boice Nicolas , DeNardo David G 
Published: January 2019

380 Background: Focal adhesion kinase (FAK) is consistently hyperactivated in multiple tumor types including pancreatic ductal adenocarcinoma (PDAC). Our preclinical work showed that FAK and PD-1 inhibitors elicit significant tumor regression, and a maximal response is achieved by combining FAK and PD-1 inhibitors with gemcitabine, suggesting the need for a cytotoxic agent to bolster antigen presentation (Jiang H et al, Nature Medicine 2016). Defactinib is an orally available, well-tolerated, potent ATP-competitive FAK inhibitor. Methods: Eligible patients are being treated according to the dose escalation schema (Table 1). A 3+3 design is being used. The study has an expansion portion for PDAC patients at the recommended phase 2 dose (RP2D). The primary endpoint is to determine the RP2D. Secondary endpoints include safety, toxicity, objective response rate, progression-free survival and overall survival. The exploratory endpoints include developing a molecular and immune profile for treatment response. Results: The dose escalation cohort has been completed with a total of 17 patients with refractory solid tumors being enrolled. The common treatment-related adverse events included fatigue (35%), nausea (29%), myalgia (29%), vomiting (24%), anorexia (24%), pruritus (24%) and fever (18%). No DLTs were observed, therefore the Level 5 dose was deemed to be the RP2D. Among the 13 patients evaluable for treatment response, 7 (54%) have stable disease. No partial or complete responses were observed to date. The median time on treatment was 127 days for all evaluable patients, and 104 days in the 6 PDAC patients with the longest time on treatment being 290 days. Paired biopsies in PDAC patients showed decreased p-FAK and changes in T cells infiltration and proliferation with treatment. Conclusions: The combination regimen is well tolerated. Dose Level 5 is the RP2D dose. The expansion cohort (PDAC only) is ongoing. Efficacy and correlative data is forthcoming. Dose LevelDefactinib D1-21 (BID)Pembrolizumab Gemcitabine (D1 and 8) Level 1 200 mg 200 mg- Level 2 400 mg 200 mg- Level 3 400 mg 200 mg 500 mg/m2 Level 4 400 mg 200 mg 750 mg/m2 Level 5 400 mg 200 mg 1,000 mg/m2 Clinical trial information: NCT02546531.
Phase II trial of pembrolizumab (PEM) plus granulocyte macrophage colony stimulating factor (GM-CSF) in advanced biliary cancers (ABC).
Authors: Kelley Robin Kate , Mitchell Emily , Behr Spencer , Hwang Jimmy , Keenan Bridget , Cheung Alexander , Gordan John Dozier , Ko Andrew H. , Cinar Pelin , Atreya Chloe Evelyn , Van Loon Katherine , Weber Thomas , Ngo Zoe , Quandt Zoe E. , Liu Chienying , Venook Alan P. , Fong Lawrence 
Published: January 2019

386 Background: The efficacy of immune checkpoint inhibition (CPI) has not been established in ABC. GM-CSF modulates immune effector cells and has demonstrated safety and improved survival (OS) in combination with ipilimumab in melanoma. This phase 2 trial aims to evaluate the efficacy and safety of PEM in combination with GM-CSF in ABC. Methods: Design: Simon’s 2-stage. Key eligibility: ABC with progression/intolerance on ≥ 1 standard therapy, no prior CPI, bilirubin ≤1.5xULN. Treatment: PEM 200 mg IV Q21 days plus 2 cycles of GM-CSF 250 µg SC D1-14 Q21 days in cycles 2 and 3 (Stage 1 Safety Cohort) or in cycles 1 and 2 (Stage 2). Endpoints: 1◦: Progression-free survival at 6 months (PFS6) with H0 25% vs. H1 50%. Key 2◦: Safety, overall response rate (ORR) and duration (DOR), OS, PD-L1 expression. Exploratory: PBMC and tumor immune cell profiles, tumor genotype, microsatellite (in)stability (MSI or MSS). Results: Accrual has completed with 27 patients (pts) enrolled 5/2016-6/2017: F/M 13/14; median age 61 (range 37-77); intrahepatic 19 (70%), extrahepatic 7 (26%), mixed 1 (4%) cholangiocarcinoma; stage IVA/B 85%, II/III 15%; median prior therapies 2 (range 1-6). Adverse events (AE): Related grade(Gr) ≥3 AE occurred in 4/27 (15%) pts including immune-related (ir)AE of Gr4 diabetes mellitus and Gr3 thrombocytopenia in 1 pt each. Gr≤2 irAE in ≥5% were: arthralgia (33%), dry eye/mouth (15%), hyperthyroid/thyroiditis (15%), hypothyroid (15%), neuropathy (11%), rash (11%), and adrenal insufficiency (7%). Steroids were required in 3/27 (11%) pts. Disposition: 19 pts removed for PD, 1 for Gr2 irAE; 7 pts remain active on treatment. Median time on treatment: 6 cycles (range 2-22+). Best response by RECIST 1.1: Partial response (PR) in 5/24 (21%) evaluable pts (1 MSI, 4 MSS); minor regression and ≥50% CA 19-9 decline in 2 additional MSS pts for 11+ and 16+ months. PBMC analyses show changes in expression of activating and inhibitory markers including PD-1 on various immune cell populations. Conclusions: PEM plus induction GM-CSF is safe and tolerable in ABC. Durable radiographic and tumor marker responses including MSS pts warrant further study. PFS6, OS, and correlative analyses are ongoing. Clinical trial information: NCT02703714.
Pilot study of gemcitabine, nab-paclitaxel, PEGPH20, and rivaroxaban for advanced pancreatic adenocarcinoma: An interim analysis.
Authors: Yu Kenneth H. , Mantha Simon , Tjan Catherine , Kaufmann Erica S. , Brenner Robin , Lowery Maeve Aine , Ku Geoffrey Yuyat , Raj Nitya Prabhakar , Shcherba Marina , Goldberg Zoe , Li Jia , Zervoudakis Alice , Hamilton Audrey M. , Won Elizabeth , Ucar Antonio , Do Richard K. G. , O'Reilly Eileen Mary 
Published: January 2019

405 Background: PEGPH20 (P) degrades hyaluronan (HA), a key component of pancreatic adenocarcinoma (PDAC) tumor microenvironment, leading to reduction of tumor interstitial pressure, decompression of tumor blood vessels and improvement in delivery of chemotherapeutics. A prior study of P with chemotherapy in PDAC (HALO-202) found an increased risk of thromboembolic (TE) events, 43%, effectively reduced with subcutaneous enoxaparin treatment. Rivaroxaban (R) is a safe and effective oral anticoagulant for treating cancer-related TE. Methods: 28 patients with advanced PDAC, KPS ≥ 70 and without prior TE were enrolled from January to June 2017. Patients received treatment with PAG (P; 3 µg/kg IV 2x/wk x 3 wks in C1, then 1x/wk x 3 wks in C2+, plus AG) every 28 days, with R (15 mg twice daily for 21 days, followed by 20 mg once daily). Primary endpoint is symptomatic TE event rate; secondary endpoints include PFS, OS, major bleeding rate and RR. Results: All 28 patients are evaluable for efficacy and safety. Key patient characteristics: age = 62 (range 45-76), M/F = 15/13, stage III/IV = 4/24, KPS 70/80/90 = 1/13/14. Median follow-up is 5.4 mo. No symptomatic and one grade 2, asymptomatic TE event (DVT) occurred (1/28 = 3.6%). Two grade 3 GI hemorrhages occurred. Best responses: partial response 11 (39%), stable disease 13 (46%), progressive disease 4 (14%), and overall disease control rate of 86%. Median PFS and OS have not been reached. Conclusions: Interim analysis shows R is safe and effectively prevents TE events in patients receiving PAG. Responses and disease control rate are encouraging in this tumor HA-level unselected patient population. Updated safety and efficacy data will be reported. Clinical trial information: NCT02921022.
A comparison of percutaneous and endoscopic-guided celiac plexus block/neurolysis in pancreatic cancer patients.
Authors: Kambhampati Swetha , Sugar Elizabeth A. , Herman Joseph , Erdek Michael A. , Shin Eun Ji , Laheru Dan 
Published: January 2019

413 Background: Pancreatic Cancer is associated with severe pain and often intractable due to its multifactorial nature. Celiac plexus neurolysis (CPN) has been shown to be effective in controlling pain and conventionally was performed percutaneously (PC) with fluoroscopic or CT guidance. However EUS guidance is being increasingly used and has shown to provide effective analgesia. The aim of this retrospective study is to compare PC-guided and EUS-guided CPN for pain control. Methods: Our retrospective cohort study included pancreatic cancer patients who underwent CPN for pain control from 2008 to 2015 at Johns Hopkins. The primary outcome was a good pain response defined as a drop in NRS pain scores to less than 1 or drop of at least 3 post-procedurally or at 1 month. Secondary outcomes were changes in opiate usage (morphine equivalents), QOL (FACT-Hep) scores and opiate-related side effects. Results: 151 patients underwent PC-CPN and 49 patients underwent EUS-CPN. Patients had their procedure on average 5 months after diagnosis. At baseline, EUS patients had significant higher median baseline pain scores, 9 (4-10) compared to 6 (5-7). A good pain response was seen in 86% of PC patients compared to 73% of EUS patients post-procedurally (p = 0.01). However, at 1 month 43% of EUS patients had a good pain response compared to 28% of PC patients, which trended towards statistical significance (p = 0.08). Following the procedure at 1 month, opiate dosage increased in both groups and no reduction in the proportion of patients with opiate related side effects was seen. EUS patients had significantly higher QOL scores at 1 month, 86 (79-92) vs 72 (67-82) (p < 0.001). Median time from procedure to death was significantly higher in EUS patients than PC patients (HR: 0.63, 95% CI: 0.44, 0.89, p = 0.008). No differences in adverse events between the two groups were seen. Conclusions: Both EUS and PC guided CPN were effective at reducing post-procedural pain in pancreatic cancer patients but their effectiveness waned by 1 month. Percutaneous patients had significantly lower pain scores immediately following the procedure. However, EUS patients seemed to have more durable pain relief with lower pain scores at 1 month and improved QOL.
Metastatic pancreatic cancer (MPC): Contrast of short- (STS) and long-term (LTS) survivor characteristics.
Authors: Kowalczyk Mark , Mandelson Margaret T. , Lin Bruce Shih-Li , Picozzi Vincent J. 
Published: January 2019

415 Background: MPC is associated with 6-12 month (mo) median overall survival (OS) in published clinical series. However, there is wide variability in OS using standard chemotherapy (CTX) regimens (e.g. gemcitabine/nab-paclitaxel, FOLFIRINOX). 10-20% of patients (pts) live ≤ 3 mo (STS); conversely 5-10% pts live ≥ 24 mo (LTS). We examined pretreatment characteristics of our institutional MPC population for their association with STS/LTS. Methods: From our institutional database, we identified over 400 pts with MPC who received CTX between the years 2003 and 2015. Pts who 1) received all of their CTX at our institution 2) had complete longitudinal follow- up available and 3) lived either ≤ 3 or ≥ 24 mo were further analyzed. A number of pretreatment characteristics were considered, including A) patient and B) disease-related factors. Results: To date,37 pts (median OS 2.0 mo)/ 41 pts (median 28.2 mo) have been identified as STS/LTS respectively. In univariate analysis factors significantly associated with STS/LTS ( p < 0.0001) were ECOG ≥2 and neutrophil /lymphocyte ratio (NLR) > 5. Age at dx, pain at dx, BMI > 30, albumin < 4.0 g/dL, Ca19.9 > 500U/mL, ascites at dx and liver involvement also were statistically significant (all p≤ 0.05 or greater). Among factors not statistically different between STS/LTS were sex, race, yr of dx, presence of diabetes or biliary obstruction at dx. A multivariate model that included ECOG ≥2 and NLR ≥5 along with other of the above factors correctly discriminated between STS and LTS with 90% accuracy (95% CI 83-97%) . Conclusions: 1) Examination of pretreatment characteristics in MPC can aid in identification of pts more likely to be STS / LTS. 2) For STS and LTS these data may aid in identifying candidates for new initial and new consolidation treatment strategies, respectively. 3) Prognostics models for STS/LTS require additional validation in independent data sets. 4) Integrating additional pretreatment information (e.g. molecular, clinical, therapeutic) may further improve OS prognostication in MPC.