bluuebunny/crossref_metadata_2025_split huggingface dataset:
FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab for patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction as second-line therapy: Interim safety and efficacy results from the phase II RAMIRIS Study (AIO-STO-0415) of the German Gastric Group at AIO.
Authors: Lorenzen Sylvie , Thuss-Patience Peter C. , Pauligk Claudia , Goekkurt Eray , Ettrich Thomas Jens , Lordick Florian , Stahl Michael , Reichardt Peter , Soekler Martin , Pink Daniel , Probst Stephan , Algül Hana , Hinke Axel , Goetze Thorsten Oliver , Al-Batran Salah-Eddin 
Published: May 2019

4023 Background: Ramucirumab as monotherapy and in combination with paclitaxel is a proven second-line option for advanced gastroesophageal adenocarcinoma (GEA). More and more patients (pts) are pretreated with docetaxel in the perioperative or first-line setting. For those pts, the benefit of a combination of ramucirumab and paclitaxel is unclear, and physicians would choose an irinotecan-based regimen as second line treatment. This provides a rationale for the evaluation of FOLFIRI + ramucirumab. Methods: This is a multicenter, randomized, investigator initiated, phase II trial, planned to include 111 pts with advanced GEA to receive 2:1 either FOLFIRI plus ramucirumab every two weeks (Arm A) or paclitaxel (days 1, 8, 15 of a 28-day cycle) plus ramucirumab every two weeks (Arm B). Primary endpoint is 6-months OS rate. This abstract displays interim results of safety and overall objective response (ORR) in docetaxel pre-treated group from up to 65 randomized pts. The results were needed to decide on conducting a subsequent phase III study. Results: 58 (A, 36; B, 22) pts were included in the safety analysis and 50 pts with tumor assessment in the response analysis. Main ≥ grade 3 adverse events were respectively in arms A/B: neutropenia (20%/22%), fatigue (6%/0%), diarrhea (8%/3%), and related SAEs (14% v 23%). Twenty-nine of 50 pts (58%) were pre-treated with docetaxel. In these pts, ORR was 30% in Arm A (5/17) and 8% (1/12) in Arm B. Disease control rate (DCR) was 65% and 50% for Arm A and B respectively. Conclusions: The interim safety analysis of the RAMIRIS trial has demonstrated feasibility of the combination of FOLFIRI and ramucirumab. Docetaxel pre-treated pts had higher ORR and DCR when ramucirumab is combined with FOLFIRI, instead of paclitaxel. EudraCT: 2015-005171-24. Clinical trial information: NCT03081143.
Treatment patterns and outcomes in Chinese gastric cancer by HER2 status: A non-interventional registry study (EVIDENCE).
Authors: Qin Shukui , Ji Jiafu , Xu Rui-hua , Wang Wei , Tang Yong , Bi Feng , Li Jin , Wang Kang , Xu Jianming , Fan Qingxia , Su Wuyun , Shen Lin 
Published: May 2019

4025 Background: Gastric cancer (GC) is the second leading cause of cancer-related deaths in China. Trastuzumab (TRA) has been used to treat HER2+ metastatic gastric cancer (mGC) in China since 2012. However, real-world data on effectiveness and safety in Chinese patients are limited. Methods: This prospective, multicenter (85 hospitals), real-world noninterventional registry study evaluated the effectiveness and safety of TRA in five cohorts of Chinese GC patients with different HER2 statuses from April 2013 to June 2018. Effectiveness analysis was conducted in three cohorts: Cohort I (HER2+ mGC with TRA), Cohort II (HER2+ mGC untreated with TRA) and Cohort IV (HER2− mGC untreated with TRA). Safety outcomes of TRA-related adverse events (AEs) were analyzed in Cohort I. Results: Cohorts I, II and IV included 709 patients (174, 113 and 422, respectively; mean age 57.8 years; 72% male); 64.9% of patients were ECOG 0–1, 93.7% had a primary GC tumor and 42.3% were at stage T4. Progressive disease was the cause of death in 32.8%, 27.4% and 29.9% in Cohorts I, II and IV, respectively. Respective mean duration of follow-up was 422.5, 287.5 and 277.5 days. Median overall survival (OS) was 22.3, 17.2 and 17.4 months, respectively. After excluding patients who had surgery, the respective median OS was 19.9, 15.3, and 12.6 months. For the first-line treatment, the median OS in Cohort I was 22.1 months, and the median progression free survival (PFS) was 8.2, 6.9 and 6.2 months in Cohorts I, II and IV, respectively. Response rates (RR) for first-line treatment in Cohorts I, II and IV were 51.7%, 18.4% and 32.8%, respectively. After propensity score matching, OS, PFS and RR were all significantly better in Cohort I versus II (all P<0.05). The most common regimen, TRA+XELOX (capecitabine+oxaliplatin), was estimated to have the longest median OS at 34.6 months. Grade ≥3 AEs were reported in 33.9% (59/174) of patients in Cohort I; anemia was the most common AE (12.1%). Conclusions: TRA improved OS and PFS in Chinese HER2+ mGC patients compared with chemotherapy alone and was well tolerated and effective when combined with a range of other therapies in a real-world setting. Clinical trial information: NCT01839500.
A phase II trial of preoperative chemoradiotherapy and pembrolizumab for locally advanced esophageal squamous cell carcinoma (ESCC).
Authors: Hong Min Hee , Kim HyeRyun , Park Seong Yong , Kim Dae Joon , Lee Chang Geol , Cho Jaeho , Kim Jong Hoon , Kim Hyeong Ryul , Kim Yong-Hee , Park Sook Ryun , Cho Byoung Chul 
Published: May 2019

4027 Background: Even though preoperative chemoradiotherapy (CRT) showed survival improvement in patients with resectable ESCC in a randomized trial over upfront surgery, ESCC still has a dismal prognosis. With the potential benefit of combining PD-1 blockade to CRT, we conducted a phase II trial which assessed the efficacy, feasibility, and safety of the combination of preoperative CRT and pembrolizumab (PEM) in ESCC. Methods: Patients (pts) with histologically confirmed ESCC (clinical stage Ib to III according to the American Joint Committee on Cancer 7th staging system) were enrolled. Pts received concurrent neoadjuvant chemotherapy (weekly paclitaxel and carboplatin), radiotherapy (44.1 Gy in 21 fractions), and PEM (every 3 week, 200 mg) during 5 weeks followed by surgery. After surgery, pts were treated with PEM during 2 years or until progression, unacceptable toxicity, death, or pts’ refusal, which came first. The primary endpoint was pathologic complete response (pCR) rate in the primary tumor and secondary endpoints were overall survival (OS), disease-free survival (DFS), the incidence of adverse events, and etc. Results: In a total of 28 enrolled pts (median age 60), 26 pts received esophagectomy. Two pts did not undergo surgery due to death (hematemesis) and consent withdrawal. There were two in-hospital mortality cases after surgery, which were resulted from acute lung injury. The pCR in primary tumor was achieved in 46.1% of pts who underwent resection (95% CI: 28.8 – 64.6). With a median follow-up of 11.7 months, median OS was not reached. Six-month and 12-month OS rates were 89.3% and 82.1%, respectively. There was a trend toward better DFS in the pCR group (n = 12) compared with the non-pCR group (n = 14) (HR = 0.33, p = 0.1). Most common treatment-related adverse events were neutropenia (50.0%) and liver enzyme elevation (30.8%) in the neoadjuvant and adjuvant period, respectively. Conclusions: The addition of PEM to preoperative CRT in ESCC demonstrated promising efficacy with acceptable toxicity. Based on the results, further investigation is warranted in a phase III clinical trial. The exploratory endpoints including biomarkers analyses are ongoing. Clinical trial information: NCT02844075.
Clinicopathological features of Epstein–Barr virus associated gastric carcinoma with submucosal invasion.
Authors: Osumi Hiroki , Kawachi Hiroshi , Yoshio Toshiyuki , Ida Satoshi , Horiuchi Yusuke , Ishiyama Akiyoshi , Hirasawa Toshiaki , Tsuchida Tomohiro , Yamamoto Noriko , Yamaguchi Kensei , Nunobe Souya , Takeuchi Kengo , Fujisaki Junko 
Published: May 2019

4029 Background: The incidence of lymph node metastasis (LNM) in pathological T1b (pT1b) gastric cancer (GC) is around 20% and the majority of them have no LNM. The Cancer Genome Atlas Research Network proposed the concept of molecular phenotype classifying GC into 4 phenotypes including Epstein-Barr virus-CIMP (EBV). EBV positive gastric cancer (EBVGC) is associated with a low prevalence of LNM; however, EBV status is not considered in the present indication of endoscopic resection (ER). We aimed to clarify the implication of EBV status for ER of pT1b GC. Methods: Consecutive cases of pT1b GCs treated with curative surgery between 2005 and 2014 were retrospectively analyzed. Tissue microarray was made and EBV-encoded RNA in situ hybridization was performed for evaluation of EBV status. Clinicopathological factors and LNM status were compared between EBVGC and non-EBVGC groups. Results: Among the 1221 pT1b GCs that underwent gastrectomy with regional lymph node dissection, 898 pT1bGCs were eligible in this study. EBVGC accounted for 7.9% (71 of 898) cases. Compared to non-EBVGC, EBVGC was more frequent in males (p = 0.0055), the upper third region (p < 0.0001), showed elevated growth features (p = 0.0059), and was associated with a lower frequency of accompanying ulceration (p = 0.002), greater depth of submucosal invasion (p = 0.017), and lower frequency of lymphatic invasion (p < 0.0001). Frequency of LNM was significantly lower in EBVGC than in non-EBVGC (4.2% vs. 21.9%, p < 0.0001). In EBVGC, tumors without lymphovascular invasion showed significantly lower frequency of LNM than those with lymphovascular invasion (0 of 50, 0%; vs 3 of 21, 14.3%; p = 0.023). Histologically, 84.5% (60 of 71) of EBVGC included carcinomas with lymphoid stroma and/or lace pattern components. Conclusions: pT1b EBVGC is a convincing candidate for ER, regardless of risk factors other than lymphovascular invasion.
A phase Ib study of IMU-131 HER2/neu peptide vaccine plus chemotherapy in patients with HER2/neu overexpressing metastatic or advanced adenocarcinoma of the stomach or gastroesophageal junction.
Authors: Chao Yee , Yau Thomas , Maglakelidze Marina , Bulat Iurie , Tanasanvimon Suebpong , Charoentum Chaiyut , Arpornwirat Wichit , Maneechavakajorn Jedzada , Dechaphunkul Arunee , Ungtrakul Teerapat , Yen Chia-Jui , Bai Li-Yuan , Chou Wen-Chi , Wiedermann Ursula , Good Anthony J , Ede Nick , Chong Leslie Mi Ok 
Published: May 2019

4030 Background: Gastric cancer is the 5th most common cancer and the 3rd leading cause of cancer deaths. HER2/neu is overexpressed in 15% - 25% of patients with gastric cancer. Monoclonal antibodies against HER2/neu are effective but alternatives are needed due to cost and global availability. IMU-131 is a B-cell peptide vaccine composed of a fusion of 3 epitopes from the extracellular domain of HER2/neu conjugated to CRM197 with the adjuvant Montanide. Polyclonal antibodies against IMU-131 peptides elicit antitumor activity in vitro and a phase I study demonstrated safety and immunogenicity in Her-2 +/++ breast cancer patients. Methods: IMU-131 was given to patients with HER2/neu overexpressing gastric or gastroesophageal junction (GEJ) adenocarcinoma in an international open-label Phase 1b dose escalation trial performed in 14 Asian and Eastern European sites assessing safety, tolerability, and immunogenicity. Each patient received IMU-131 on Days 0, 14, and 35, accompanied by cisplatin and 5-fluorouracil or capecitabine every 21 days. Results: 14 patients were enrolled with advanced stage IIIb or IV with 10 HER2 overexpressing tumors (7 x HER2+++, 3 x HER2++ FISH positive) and 4 HER2++ expressing tumors. Mean age was 57 yo (range of 21 - 79) with ECOG scores of 0 or 1 in 7 patients each. There were 9 Asian and 5 Caucasian patients with 5 females and 9 males. Dose levels were 0.1, 0.3 and 0.5 mg with 3, 6, and 5 patients receiving those dose levels each. 11 patients received all 3 doses with 3 patients who received only 2 doses due to disease progression and 2 patients received a dose on day 182. Of the 14 patients dosed 11 were evaluable for tumor progression at day 56 and later. Of those patients, the best response was 1 CR, 4 PR,5 SD and 1 PD. In the 0.1 mg dose group the best response was 1 CR and 2 SD, with 2 PR, 2 SD and 1 PD in the 0.3 mg group and 2 PR and 1 SD in the 0.5 mg group. In patients with HER2 overexpression there was 1 CR, 4 PR, 2 SD and 1 PD, and in patients with HER2++ expression there was 3 SD. There were no SAEs related to IMU-131 and 1 patient had a mild injection site reaction. Conclusions: IMU-131 is a promising B-Cell vaccine against HER2. Further work in a controlled phase 2 trial is ongoing. Clinical trial information: NCT02795988.
Camrelizumab combined with capecitabine and oxaliplatin followed by camrelizumab and apatinib as first-line therapy for advanced or metastatic gastric or gastroesophageal junction cancer: Updated results from a multicenter, open label phase II trial.
Authors: Shen Lin , Peng Zhi , Zhang Yan-Qiao , Wei Jia , Wang Feng , Ying Jieer , Deng Yanhong , Gu Kangsheng , Cheng Ying , Yuan Xianglin , Xiao Juxiang , Wang Linna , Zou Jianjun 
Published: May 2019

4031 Background: Capecitabine plus oxaliplatin (CAPOX) is one of the standard first-line treatments for advanced or metastatic gastric cancer. Camrelizumab (SHR-1210, an anti–PD-1 antibody) shows promising anti-tumor activity in patients (pts) with advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer. Camrelizumab combined with CAPOX for untreated G/GEJ cancer was assessed as a part of an ongoing multicenter, open-label phase 2 trial (cohort 1), and encouraging preliminary results were reported. Here, we present the updated safety and efficacy data. Methods: In this cohort, systemic treatment naïve pts with HER2– advanced or metastatic G/GEJ adenocarcinoma were given camrelizumab 200 mg on Day 1, capecitabine 1000 mg/m2 bid on Days 1–14 and oxaliplatin 130 mg/m2 on Day 1 of each 21-day-cycle for 4 to 6 cycles followed by camrelizumab 200 mg every 3 weeks plus apatinib 375 mg qd until disease progression or intolerable toxicity. The primary endpoint was objective response rate. Results: At data cutoff (Jan 20, 2019), 43 of the 48 enrolled pts were evaluable. Partial response was observed in 28 pts (65%), and 19 (44%) were confirmed. Stable disease in 14 pts and progressive disease in 10 pts were reported. Median estimates for duration of response and progression-free survival were not reached. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 9 pts (21%), included neutropenia, diarrhea, rash and elevated ALT, whereas none of the TRAEs was fatal. Ten pts without progression after 4–6 cycles of camrelizumab and CAPOX combination therapy all received camrelizumab plus apatinib as sequential therapy, and no new safety signals were observed. Conclusions: The updated results confirmed that camrelizumab plus CAPOX followed by camrelizumab plus apatinib was well tolerated with noteworthy responses as first-line therapy in advanced or metastatic G/GEJ cancer pts. Expansion of this cohort in a phase 3 study are under way. Clinical trial information: NCT03472365.
Trifluridine/tipiracil (FTD/TPI) in patients (pts) with metastatic gastroesophageal junction cancer (mGEJC): Subgroup analysis from TAGS.
Authors: Mansoor Wasat , Arkenau Hendrik-Tobias , ALSINA MARIA , Shitara Kohei , Tejani Mohamedtaki Abdulaziz , Thuss-Patience Peter C. , Cuffe Sinead , Dvorkin Mikhail , Park David , Ando Takayuki , Van Den Eynde Marc , Beretta Giordano D. , Zaniboni Alberto , Doi Toshihiko , Tabernero Josep , Ilson David H. , Makris Lukas , McGuigan Sandra , Van Cutsem Eric 
Published: May 2019

4038 Background: The incidence of GEJC is increasing in North America and Europe, especially among white men. Many pts present with metastatic disease or relapse locally or systemically after resection of early-stage disease. The global phase 3 study TAGS (NCT02500043) demonstrated the efficacy and safety of FTD/TPI in previously treated pts with metastatic gastric cancer (mGC)/mGEJC. Here we report results in the mGEJC subgroup from TAGS. Methods: Pts with mGC/mGEJC treated with ≥2 prior chemotherapy regimens were randomized (2:1) to receive FTD/TPI (35 mg/m2 BID on days 1–5 and 8–12 of each 28-day cycle) or placebo, plus best supportive care. A preplanned efficacy and safety analysis was performed in pts with mGEJC. Results: Of 507 randomized pts, 145 (29%) had GEJC as the sole primary disease site (FTD/TPI, 98/337; placebo, 47/170). Of pts with mGEJC, 85% were male and 83% were white (overall population, 73% and 70%). Baseline characteristics were generally balanced for pts with mGEJC across treatment groups, except for fewer pts having prior gastrectomy (40% vs 55%) and more pts having received ≥3 prior regimens (74% vs 66%) in the FTD/TPI group than in the placebo group. FTD/TPI had an efficacy benefit in pts with mGEJC, and the FTD/TPI safety profile was similar in this subgroup and the overall population (table). Conclusions: FTD/TPI showed a manageable safety profile and efficacy benefit in pts with mGEJC in the TAGS trial, despite heavier pretreatment of the FTD/TPI than the placebo group. Clinical trial information: NCT02500043. [Table: see text]
Homologous recombination deficiency as prognostic marker in metastatic gastric cancer.
Authors: Sousa Nuno , Faustino Catia , Aguas Lucia Maria Nunes , Freire João , Coutinho Camila , Faustino Ilda , Capela Andreia , Costa Telma , Costa Andreia Sofia Alves , Coelho Sara , Pereira Filipa , Abreu Sofia Coelho , Rolo Ana Sofia , Albergaria Andre , Lima Jorge , Wen Xiaogang , Mesquita Carina , Dias Claudia Camila , Azevedo Luis Filipe , Carneiro Fatima 
Published: May 2019

4040 Background: Gastric cancer is the 5th cancer diagnosis and 3rd cause of cancer death worldwide. Metastatic gastric cancer (mGC) has a median survival of 11 months. mGC is an heterogeneous disease and different biologic characteristics may justify differential therapeutic opportunities. Tumors with homologous recombination (HR) deficiency may benefit with treatment with PARP inhibitors or immune checkpoint inhibitors. The purpose of this study was to evaluate the prevalence and prognostic impact of altered expression of HR proteins as surrogates for homologous recombination deficiency (HRD) in mGC. Methods: Multicenter retrospective cohort of mGC treated with platinum-based chemotherapy. HRD defined as absence of at least one of the following proteins: ATM, ATR, CHK2, RAD51, RAD52, BRCA1, BRCA2, MRE11 by immunohistochemistry. Survival time calculated as the difference between first cycle of platinum-based chemotherapy and death or last observation. Association between HRD and survival examined with log-rank test. Results: 440 patients included, of which 70% male, with mean age of 58 years (SD: 11). 75% of patients had mGC at diagnosis, 43% had 2 or more organs involved and 63% were registered as ECOG 0 or 1 at the start of first line chemotherapy. The most common histologic subtype was tubular adenocarcinoma (44%) followed by diffuse carcinoma (32%). HRD was noted in 196 (45%) cases (95%CI: 40%-49%). The most commonly altered proteins were ATM (21%) and BRCA2 (18%). In HRD tumors, 99 (51%) had altered expression of only one HR protein; 47 (24%) had altered expression of two HR proteins; the remaining cases had altered expression of 3 or more proteins. After a median follow up of 11 months, median survival for the cohort was 11 months (95% CI 9-12). HRD was associated with an improved survival, HR = 0.61 (95%CI: 0.48-0.78, p < 0.001), that remained significant after adjustment for sex, age, performance status and disease status (HR = 0.63; 95%CI: 0.48-0.82; p < 0.001). Conclusions: HRD phenotype was present in 45% of mGC cases and is associated with improved prognosis for mGC treated with platinum-based first line chemotherapy.
Analysis of symptoms and functional HRQoL scales in TAGS, a phase III trial of trifluridine/tipiracil (FTD/TPI) in metastatic gastric cancer (mGC).
Authors: Alsina Maria , Tabernero Josep , Shitara Kohei , Doi Toshihiko , Dvorkin Mikhail , Mansoor Wasat , Arkenau Hendrik-Tobias , Prokharau Aliaksandr , Ghidini Michele , Faustino Catia , Gorbunova Vera , Zhavrid Edvard , Nishikawa Kazuhiro , Ando Takayuki , Yalcin Suayib , Van Cutsem Eric , Skanji Donia , Leger Catherine , Sabater Javier , Ilson David H. 
Published: May 2019

4043 Background: The phase 3, randomized, double-blind, placebo-controlled study (TAGS) evaluated the efficacy and safety of FTD/TPI (35 mg/m² given orally twice a day on days 1–5 and 8–12 of a 28-day cycle) in mGC patients who had previously received≥2 prior regimens for advanced disease and demonstrated a clinically relevant and statistically significant benefit in OS and PFS with a predictable and manageable safety profile. HRQoL data and association between QoL and time to ECOG status deterioration (2 or more) are reported here. Methods: HRQoL was evaluated using EORTC QLQ-C30 and the gastric-specific module (QLQ-STO22) questionnaires at baseline and at every 4 weeks thereafter until treatment discontinuation. Prespecified key HRQoL were changes from baseline and time to deterioration. Changes ≥10 points were deemed clinically relevant. A time-dependent Cox-regression analysis was performed to evaluate the association of 10-point Global Health Status deterioration with worsening ECOG status. Results: Of 507 patients randomized, 332/337 (98.5%) of FTD/TPI and 164/170 (96.5%) of placebo had baseline QoL data. Overall compliance was 84% for both questionnaires. Demographic and disease were generally balanced between the two groups; QoL scores were also similar between groups. HRQoL was largely maintained during treatment in both arms for most items; mean changes from baseline remained under the 10-point threshold. Clinically relevant changes from baseline were observed only for pain relief at cycle 2 (favouring FTD/TPI); and improved role functioning at cycle 3 (favouring placebo). In a sensitivity analysis including death or progression as an event, FTD/TPI was associated with a positive trend suggesting a reduced risk of QoL deterioration across all scales compared to placebo (HRs ranged from 0.57 to 0.74. A 10-point Global Health Status deterioration was associated with a worsening ECOG status (HR, 95% CI, 1.5, 1.2 to 1.86). Conclusions: During the treatment period, HRQoL remained stable for most functional and symptom scales in both arms, suggesting that HRQoL is largely maintained with FTD/TPI. Treatment with FTD/TPI was associated with a positive trend toward a lower risk of QoL deterioration than placebo across all scales. Changes in QoL were informative for patients ‘expected ECOG status. Clinical trial information: NCT02500043.