bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety for trifluridine/tipiracil (TAS-102) with bevacizumab combination in patients with refractory metastatic colorectal cancer in real-world clinical practice: The single-institutional experience.
Authors: Yasuda Kayo , Kotani Daisuke , Kuboki Yasutoshi , Fukuoka Shota , Bando Hideaki , Kawazoe Akihito , Nakamura Yoshiaki , Shitara Kohei , Yoshino Takayuki 
Published: January 2019

865 Background: Trifluridine/tipiracil (TAS-102) is an oral combination therapy approved for the treatment of patients with metastatic colorectal cancer (mCRC). Phase 1/2 C-TASK FORCE study of TAS-102 plus bevacizumab for patients with refractory mCRC demonstrated a promising efficacy results with mild toxicity profile (Kuboki Y, et al. Lancet Oncology, 2017). The retrospective single-institutional study is aiming to investigate safety of TAS-102 plus bevacizumab for patients with refractory mCRC in real-world clinical practice. Methods: MCRC patients who were refractory or intolerant to a fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (if wild-type RAS) and consecutively received TAS-102 plus bevacizumab between January 2016 and June 2017, were analyzed. Adverse events (AEs) were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Results: A total of 33 patients were identified for safety analysis. Patient characteristics were as follows; male/female, 19/14; median age, 59.0 (range 38-81); ECOG Performance Status of 0/1, 21/12; and All wild/ RAS mutant/ BRAF mutant/ unknown, 16/15/1/1. Six patients had received prior regorafenib. The relative dose intensities of TAS-102 and bevacizumab were 87% and 79%, respectively. Grade 3 or higher hematological and non-hematological AEs were follows; leucopenia, 33%; neutropenia, 42%; anemia, 9%; and proteinuria, 12%. There were no febrile neutropenia or treatment-related death. G-CSF was given in 8 patients (24%), while intravenous antibiotics was in one patient. There were four patients with emergency admission, and out of these, the two patients had intestinal perforation, and perianal abscess, which were regarded as treatment-associated; ultimately these AEs were fully recovered. Conclusions: Our findings suggested safety for TAS-102 plus bevacizumab combination in real-world clinical practice is consistent with those in clinical trial setting.
Clinical outcomes of gastric cardia cancer during a recent decade of Korea.
Authors: KO Sung Woo 
Published: January 2019

87 Background: To date, the incidence of adenocarcinomas of the gastric cardia has been increasing worldwidely. In 7th edition of the American Joint Commission on Cancer, a tumor within 5 cm of the EGJ is classified and staged according to the esophageal cancer. There are two different etiologies of gastric cardia cancer - Barrett's esophagus and Helicobacter pylori (H. pylori) associated intestinal metaplasia. We aimed to evaluate the clinical characteristics and outcome between gastric cardia and non-cardia cancer. Methods: We performed a retrospective cohort study of 90 patients with gastric cardia cancer from Jan. 2003 to Dec. 2013. We selected 180 patients with gastric non-cardia cancer as age and sex matched control during the same period (by AGE, SEX PROGRAM). Results: The rate of curative resection (R0) was significantly low in gastric cardia cancer (74/81 vs. 146/149) (91.4% vs 98.0%, P=.02) The recurrence rate was lower in patents with non-cardia cancer than those with cardia cancer (21/74 vs. 12/146) (28.4% vs 8.0%, P=.00). Subgroup analysis was done for patients with cardia cancer according to BMI and helicobacter infection and atrophic mucosal change. The median follow up period of obese patients and non-obese patients were 35.0month and 28.0month, which revealed there was no difference (P=.70). We determined patients with mucosal atrophic change and HP infection as a group1, and patients with no mucosal change with non- infective status as a group 2. The median follow up period of group 1 patient and group 2 patients were 26.0month and 36.0month, there was no significant difference. (P=.96). Conclusions: Gastric cardia cancer had a negative prognostic impact, compared with gastric non-cardia cancer. Although a possible heterogeneity in the pathogenesis and biological behavior of gastric cardia cancer would be present, there was no difference in prognosis.
Interim safety and clinical activity in patients (pts) with locally advanced and unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma from a multicohort phase I study of ramucirumab (R) plus durvalumab (D).
Authors: Bang Yung-Jue , Golan Talia , Lin Chia-Chi , Kang Yoon-Koo , Wainberg Zev A. , Wasserstrom Heather , Jin Jin , Mi Gu , McNeely Samuel , Laing Naomi , Goff Laura Williams , Fu Siqing 
Published: January 2019

92 Background: Angiogenesis and immunosuppression are hallmarks of tumor growth. This global phase 1 trial evaluates the combination of R (anti-VEGFR2) and D (anti-PD-L1) in pts with G/GEJ by simultaneously targeting these two processes. Methods: This ongoing, multi-cohort, phase 1a/b trial (NCT02572687) enrolled pts with confirmed G/GEJ adenocarcinoma with prior progression on 1 or 2 lines of systemic therapy, measurable disease, ECOG PS 0-1, and baseline tumor tissue. PD-L1 expression was assessed using the SP-263 IHC; MSI status was determined using PCR. Enrolled pts received R (8 mg/kg IV) and D (750 mg IV) every two weeks on a 28-day cycle. Primary objective was to assess safety and tolerability of R+D; preliminary efficacy was also examined. Results: As of 26-May-2017, 29 G/GEJ adenocarcinoma pts were treated. The median age was 55 y; 69% were male; 66% had ECOG PS of 1; 48% had PD-L1 ≥25% expression in tumor or immune cells, 3.5% were MSI-high; and 72% received study treatment as second line for advanced disease. Median duration of treatment was 2.5 mo for R and 3.0 mo for D. Treatment-emergent adverse events (TEAEs) occurred in 29 (100%) pts and 21 (72%) pts experienced grade 3/4 TEAEs, while treatment-related AEs (TRAE) occurred in 24 (83%) pts; none resulted in treatment discontinuation. Ten (35%) pts had grade 3 TRAEs, and no grade 4 or 5. All grade TRAEs occurring in ≥10% of pts were hypertension (34%), fatigue (31%), headache (24%), diarrhea (21%), pyrexia (10%) and decreased appetite (10%). Five pts (17%) reported a serious adverse event related to study treatment. Preliminary efficacy data (RECIST v1.1) showed 5 of 29 pts (17%) achieved a confirmed PR. Only 1 responding pt was MSI high. The overall response rate for pts with PD-L1 ≥25% was 36%. Median PFS was 2.6 mo (95% CI, 1.45 to 6.28). As of data cut-off, 6 pts (21%) remain on treatment. Conclusions: R+D generated no unexpected toxicity, and demonstrated antitumor activity in pts with previously treated advanced G/GEJ adenocarcinoma. Clinical trial information: NCT02572687.
A real-world comparison of multi-modality therapies in locally advanced gastro-esophageal junction (GEJ) cancers.
Authors: Samawi Haider , Tilley Derek , Tang Patricia A. , Spratlin Jennifer L. , Lee-Ying Richard M. , Cheung Winson Y. 
Published: January 2019

96 Background: Trials show that addition of systemic therapy and/or radiation to surgery improves survival in GEJ cancers. However, the different regimens have not been directly compared. We examined population-based outcomes of 3 treatments: 1) neoadjuvant carboplatin and paclitaxel plus radiation (CROSS); 2) perioperative epirubicin, cisplatin, and fluoropyrimidine (MAGIC); and 3) cisplatin and fluoropyrimidine with radiation (CisFP). Methods: We reviewed patients diagnosed with GEJ cancer from 2005 to 2015 who received CROSS, MAGIC, or CisFP at 2 tertiary, 4 regional, and 11 community cancer centers in Alberta, Canada. Survival was assessed with Kaplan-Meier curves and compared with the log-rank test. A Cox proportional hazards model was constructed to evaluate the impact of treatment on overall survival (OS). Results: 331 patients were identified. Median age was 63 (IQR 56-69) years and 86% were men. CROSS was used in 217 (65%) cases followed by CisFP in 72 (22%) and MAGIC in 42 (13%). Age, sex, and stage were not associated with treatment selection (all p > 0.05), but a higher proportion of CROSS and CisFP patients had adenocarcinoma (86% and 85%, respectively) compared to MAGIC patients (41%) ( p < 0.01). CROSS and MAGIC correlated with higher surgical resection rates when compared to CisFP (82% vs. 79% vs. 50%, respectively, p < 0.01). Median OS favored CROSS and MAGIC rather than CisFP, but this was not statistically significant (29 vs. 34 vs. 20 months, respectively, p= 0.17). Adjusting for confounders, OS remained similar for MAGIC (HR 0.8, 95%CI 0.5-1.3, p= 0.36) and CisFP (HR 0.7, 95%CI 0.5-1.1, p= 0.10) when compared to CROSS. In addition, age > 65, advanced stage, and lack of surgical resection were associated with increased risk of death (HR 1.5, 95%CI 1.1-2.0, p= 0.02, HR 2.2, 95%CI 1.2-3.9, p< 0.01 and HR 4.1, 95%CI 2.8-5.9, p< 0.01, respectively). Conclusions: OS was similar across all 3 regimens, but outcomes were inferior to those seen in original trials. This observation suggests that GEJ patients in routine practice are different from study participants or that treatment selection may be driven by factors other than trial eligibility criteria.
Phase II study of epacadostat with pembrolizumab in metastatic or unresectable gastroesophageal junction and gastric adenocarcinoma requiring paired biopsies.
Authors: Kardosh Adel , Tseng Diane , Sahaf Bita , Zomet Ativ , Krupa Julia , Fisher George A. , Wang David S , Mackall Crystal , Kunz Pamela L. 
Published: January 2019

TPS191 Background: Gastroesophageal junction (GEJ) and gastric adenocarcinomas constitute a major health problem worldwide. Gastric cancer is the fourth most prevalent malignancy and the second leading cause of cancer death worldwide. Furthermore, the incidence of adenocarcinoma of the esophagus, GEJ and gastric cardia has risen faster than any other malignancy in the last 25 years in the United States and other Western countries. Cytotoxic chemotherapy remains the standard treatment, with progression free survival (PFS) for advanced disease of 4 to 6 months and median overall survival (OS) of 7 to 10 months. Pembrolizumab, a PD-1 inhibitor, was recently approved for advanced gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-1, on the basis of a response rate of 13% seen in KEYNOTE 059 (NCT02335411). Combination immunotherapies are hypothesized to build on this response. Methods: This is a single arm, phase II clinical trial of epacadostat, a novel inhibitor of the enzyme indoleamine 2,3 dioxygenase-1 (IDO-1), in combination with pembrolizumab, in metastatic or unresectable gastroesophageal junction or gastric adenocarcinoma. A 6-month PFS of 20% with single agent pembrolizumab is the basis for the null hypothesis. We will enroll 30 patients over 18 months and follow patients for at least 6 months. This design has 80% power to reject a 20% PFS rate, if the true PFS is 39%. Eligible patients must have: adenocarcinoma of the distal esophagus, gastroesophageal junction or stomach; progression on at least one line of prior therapy for metastatic disease, and for HER2+ disease should have received prior trastuzumab; ECOG performance status 0 or 1; willing to undergo two newly-obtained biopsies - before and on-treatment, provided the procedure is not deemed high-risk and is clinically feasible. Notably, PDL-1 expression is not required. The primary endpoint is 6-month PFS, with secondary endpoints of response rate (RR), OS, and the safety and tolerability of the combination. Furthermore, comprehensive immune profiling from patient blood and tumor tissue will be performed. The study opened to accrual in September 2017 (NCT03196232). Clinical trial information: NCT03196232.
JAVELIN Gastric 100: Phase 3 trial of avelumab (anti-PD-L1) maintenance therapy versus continuation of first-line chemotherapy in patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC).
Authors: Moehler Markus H. , Ryu Min-Hee , Lee Keun-Wook , Coskun Hasan Senol , Wong Rachel , Ozguroglu Mustafa , Chung Hyun-Choel , Poltoratsky Artem , Tsuji Akihito , Yen Chia-Jui , Muntean Alina , le Sourd Samuel , Vaccaro Gina M. , Taieb Julien , Boku Narikazu , Sharma Maitreyi , Xiong Huiling , Conti Ilaria , Bang Yung-Jue 
Published: January 2019

TPS195 Background: Outcomes with first-line (1L) chemotherapy for GC/GEJC are limited and new strategies to increase efficacy without added toxicity are needed. Avelumab, a human anti-PD-L1 IgG1 monoclonal antibody, is approved for metastatic Merkel cell carcinoma (US and EU) and advanced urothelial carcinoma after progression on platinum therapy (US). In phase 1 studies in advanced GC/GEJC, avelumab showed antitumor activity and a manageable safety profile, including in a subgroup of patients (pts) without progression on 1L chemotherapy who received avelumab as maintenance therapy. JAVELIN Gastric 100 (NCT02625610) is a global, randomized, open-label, phase 3 trial comparing maintenance therapy with avelumab vs continuation of 1L chemotherapy in pts with advanced GC/GEJC who have not progressed after 12 weeks of 1L oxaliplatin/fluoropyrimidine chemotherapy. Methods: Eligible pts have histologically confirmed, unresectable, measurable, locally advanced or metastatic GC/GEJC adenocarcinoma, no prior chemotherapy for advanced disease, no prior therapy targeting T-cell coregulatory proteins, and ECOG PS of 0–1. Pts are not preselected based on PD-L1 expression and pts with HER2+ tumors are excluded. Approximately 466 pts who achieve at least stable disease following 12 weeks of 1L oxaliplatin/fluoropyrimidine chemotherapy will be randomized 1:1 to receive maintenance therapy with either avelumab 10 mg/kg by IV infusion Q2W or continuation of 1L chemotherapy. Maintenance therapy is given until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are overall survival and progression-free survival. Secondary endpoints include best overall response, quality of life measures, safety (NCI-CTCAE v4.03), and tumor biomarkers. Responses are evaluated per RECIST 1.1 and adjudicated by independent review committee. Enrollment is ongoing at sites in North/South America, Asia-Pacific, and Europe. Clinical trial information: NCT02625610.
A phase 2 trial of CRS-207 and pembrolizumab in adults with recurrence of metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinomas.
Authors: Kelly Ronan Joseph , Abrams Thomas Adam , Catenacci Daniel V.T. , Wainberg Zev A. , Lin Bruce Shih-Li , Enstrom Amanda , Whiting Chan C. , Wason Prieya , Murphy Aimee , Brockstedt Dirk G. , Moon Anne , Walling Jackie , Lai Rose , Ku Geoffrey Yuyat 
Published: January 2019

TPS200 Background: CRS-207 is a live, attenuated, double-deleted Listeria monocytogenes (LADD) strain with a mesothelin expression cassette inserted. CRS-207 has a well-established, manageable toxicity profile and can elicit mesothelin-specific cell-mediated immunity. Clinical activity of CRS-207 has been shown in a separate Phase 1 trial of mesothelioma. In gastroesophageal (GE) cancers, mesothelin expression is estimated between 30% – 50% and has been correlated with poor prognosis. Preclinical models suggest the combination of LADD-based immunotherapeutics and a PD1 inhibitor may induce more sustained anti-tumor responses than either LADD or PD1 inhibitor monotherapy. GE cancers are responsive to PD1 inhibitors in a subset of patients; this trial proposes to evaluate the efficacy of CRS-207 combined with pembrolizumab in patients with relapsed GE cancer, and to correlate clinical activity with mesothelin expression level. Methods: This Phase 2, open-label, single-arm, multicenter clinical study (NCT 03122548) will enroll approximately 79 subjects at 20 sites. Adults with histologically-confirmed, advanced gastric, GEJ, or esophageal adenocarcinomas are eligible. Subjects must have received 1 or 2 prior treatment regimens, which must have included a platinum and a fluoropyrimidine. Subjects must have disease progression with measurable tumors. A pre-treatment biopsy of either the primary tumor or metastatic site is required prior to dosing. Subjects with prior exposure to checkpoint inhibitors or other immunotherapies are excluded. From cycle 1 to 4 during the treatment and evaluation period, pembrolizumab (IV 200 mg) and CRS-207 (IV 1 x 109 CFU) are both administered in 3-week cycles. Afterward, pembrolizumab will be administered once every 3 weeks; CRS-207 will be given once every 6 weeks. CT scans will be performed every 6 weeks to monitor disease status. The primary endpoint is objective response rate defined by RECIST 1.1. Clinical trial information: NCT03122548.
GastroPET: Phase II academic clinical trial evaluating sequential FDG-PET driven preoperative treatment strategy in locally advanced oesophago-gastric cancer in the context of miRNA- and immune-based biomarkers.
Authors: Obermannova Radka , Hejnova Renata , Zdrazilova-Dubska Lenka , Demlova Regina , Slaby Ondrej , Studentova Hana , Petruzelka Lubos , Grell Peter , Vyzula Rostislav 
Published: January 2019

TPS202 Background: The standard treatment approach in locally advanced oesophago-gastric cancer (OGC) contains surgery with perioperative chemotherapy (CXT). Nonetheless according to sequential 18FDG-PET-CT only 40–50% of the patients respond to CTX and non-responding patients would perhaps profit from concurrent radiotherapy (CRT). This phase II trial evaluates the sequential FDG-PET driven preoperative treatment strategy of early histopathological response and improved survival. Methods: Approximately 70 pts with resectable locally advanced OGC will be enrolled in this interventional, prospective, non-randomized multicenter trial. Pts will undergo baseline FDG-PET scan and will be given 1 cycle of CXT (FLOT or FOLFOX). FDG-PET scan will be repeated after 14 days and FDG-PET responders with ≥ 35% reduction in SUVmax from baseline to initial treatment will continue with CXT prior to surgery. FDG-PET non-responders will switch to the CRT (weekly carboplatin and paclitaxel with concurrent radiotherapy (45 Gy in 25 fractions) prior to surgery. The main goal of the surgical therapy is to obtain negative surgical margins. Selected miRNAs and immune parameters will be evaluated for their predictive value. Eligibility: biopsy-proven locally advanced resectable oesophago-gastric adenocarcinoma (Siewert I – III) stage Ib – IIIc; endoscopy and endoscopic ultrasound; pts to be fit for the platinum-containing CXT; potentially R0 resectable tumors. The primary objective: the predictive value of FDG-PET dynamics in the preoperative setting for early regression and R0 resection rate. Secondary endpoints: i/ identification of tissue/plasma miRNA and immune-based biomarkers, ii/ disease free survival and overall survival. Status: Opened to accrual in Oct 2017. Clinical trial information: Eudra CT 2017-001264-38. This work was supported by Ministry of Health, Project No: 15 P03-17-29389A and projects LO1413, DRO and LM15089 BBMRI-CZ. Clinical trial information: 2017-001264-38.
Phase II trial of conversion surgery after apatinib in combination with S-1/oxaliplatin (SOX) for patients with unresectable gastric cancer (Ahead-BG301 trial).
Authors: Chen Lin , Zhang Kecheng , Wei Bo , Guo Xin , Xi Hongqing , Li Jiyang , Cui Jianxin , Gao Yunhe , Liang Wenquan , Lu Yixun 
Published: January 2019

TPS203 Background: Recent study has showed that selected patients with unresectable gastric cancer could benefit from surgical resection after achieving response following induction chemotherapy. We speculated that apatinib, an inhibitor of VEGFR-2, in combination with chemotherapy could increase response rate and resection rate following systemic therapy. This trial is designed to investigate the efficacy and safety of conversion surgery after apatinib plus S-1/oxaliplatin (SOX) for patients with unresectable gastric cancer (NCT03007446). Methods: This is a prospective, single-arm and open-label Phase II clinical trial. The primary outcome is resection rate after induction chemotherapy for patients with unresectable gastric cancer. The secondary outcomes include objective response rate and overall survival. Main eligibility criteria include patients with at least single non-curative factor confirmed by CT, MRI, PET-CT or staging laparoscopy: unresectable diseases with locally advanced gastric cancer (T4b); hepatic metastasis (H1; less than five lesions, total diameter ≤ 8 cm); peritoneal metastasis (CY1, P1). An estimated enrollment of 20 patients was planned. After receiving two cycles of apatinib (500 mg, oral, qd) plus SOX (S-1: 40mg bid, d1-14 q3W; oxaliplatin: 130 mg/m2, d1 q3W), patients will be subject to multidisciplinary team evaluation for surgery. First patients were enrolled in Dec 2016. Data analysis was planned in Nov 2018. Clinical trial information: NCT03007446.
Phase Ib trial of pembrolizumab and XL888 in patients with advanced gastrointestinal malignancies.
Authors: Akce Mehmet , Alese Olatunji B. , Shaib Walid Labib , Wu Christina Sing-Ying , Lesinski Gregory B , El-Rayes Bassel F. 
Published: January 2019

TPS526 Background: Heat shock protein 90 (HSP90) has a central role in modulating tumor microenvironment, inflammatory signaling pathways (NF-κB, HIF-1α and Jak-STAT), tumor antigen presentation and expression, PD-L1 expression and macrophage migration inhibitory factor (MIF) as well as cytokine production. Inhibitors of HSP90 have been shown in preclinical studies and in patient samples to exert anti-tumor effects and modulate signaling pathways. XL888 is a selective inhibitor of HSP90. Based on this preclinical rationale, we have developed a phase Ib/II trial to determine the recommended phase II dose, evaluate the safety, toxicity profile, preliminary antitumor activity, and immunogenicity of the XL888 and Pembrolizumab combination in previously treated patients with advanced gastrointestinal tumors. Methods: The phase Ib trial design is standard 3+3. XL888 is administered orally (PO) in three dose levels of 45 (DL1), 90 (DL2), 60 (only if DLT on DL2) mg twice weekly with pembrolizumab at 200 mg IV on day 1, in 21-day cycles. Eligible patients must have stage IV or locally advanced unresectable gastrointestinal adenocarcinomas who have failed at least one prior therapy (patients with colorectal adenocarcinoma must have previously received oxaliplatin, irinotecan, and fluoropyrimidine), age ≥18 years, ECOG PS 0-1, no prior anti PD-1 or anti-PD-L1 agent. After recommended phase II dose is established, an expansion phase will enroll 16 patients with pancreatic adenocarcinoma (Arm A) and 16 patients with colorectal adenocarcinoma (Arm B). Primary endpoint response rate. In the expansion phase patients will receive initial cycle (3 weeks) treatment with either pembrolizumab or pembrolizumab plus XL888 and then starting cycle 2 all patients receive the combination. Blood will be collected pre-treatment, post 1st and 2nd cycle. Eight patients in each arm will undergo pre and post treatment tumor biopsies. This design will enable us to evaluate the effects of pembrolizumab alone versus the combination. This study was activated in June 2017 and to date 4 patients were enrolled in dose escalation phase. The dose expansion phase is expected to start accrual in December 2017. Clinical trial information: NCT03095781.