bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nivolumab (nivo) in sorafenib (sor)-naive and -experienced pts with advanced hepatocellular carcinoma (HCC): CheckMate 040 study.
Authors: Crocenzi Todd S. , El-Khoueiry Anthony B. , Yau Thomas Cheung , Melero Ignacio , Sangro Bruno , Kudo Masatoshi , Hsu Chiun , Trojan Jorg , Kim Tae-You , Choo Su-Pin , Meyer Tim , Kang Yoon-Koo , Yeo Winnie , Chopra Akhil , Baakili Adyb , Dela Cruz Christine Marie , Lang Lixin , Neely Jaclyn , Welling Theodore 
Published: September 2018

4013 Background: Many pts with advanced HCC progress on SOC therapy. Nivo is a fully human anti–PD-1 IgG4 mAb that demonstrated durable responses (20% ORR with a median DOR of 9.9 mo; 9-mo OS rate was 74%) in pts with advanced HCC in the dose-expansion (EXP) phase of the CheckMate 040 study (NCT01658878; Melero et al. 2017). Here we present survival and durability of response data in both sor-naive and -experienced pts with advanced HCC in CheckMate 040. Methods: Pts naive to or previously treated with sor received nivo in phase 1/2 dose-escalation (ESC; 0.1–10 mg/kg) and -EXP (3 mg/kg) cohorts Q2W regardless of PD-L1 status. Primary endpoints were safety/tolerability (ESC) and ORR (EXP; ORR by investigator [INV] and blinded independent central review [BICR]) using RECIST v1.1. Secondary endpoints included DOR, DCR, and OS. Biomarkers were assessed using pre-treatment tumor samples. Results: Overall, pts (N=262) had a median follow-up of 12.9 mo, and 98% had Child-Pugh scores 5–6. In sor-naive pts (n=80), the ORR (INV) was 23%, with 44% of responses (8/18) ongoing (Table). The DCR was 63%; 40% of pts had stable disease ≥6 mo. In sor-experienced pts (n=182; 91% progressed on sor), the ORRs (INV) were 16%–19%. Overall, responses occurred regardless of etiology or tumor cell PD-L1 expression. Nivo had a manageable safety profile consistent with that reported in other tumor types. Updated data with additional 4 mo of follow-up will be presented. Conclusions: Nivo demonstrated durable responses with long-term survival and favorable safety in both sor-naive and -experienced pts with advanced HCC. Clinical trial information: NCT01658878. [Table: see text]
Results of interim analysis of the multicenter randomized phase III SENORITA trial of laparoscopic sentinel node oriented, stomach-preserving surgery versus laparoscopic standard gastrectomy with lymph node dissection in early gastric cancer.
Authors: Ryu Keun Won , Kim Young Woo , Min Jae Seok , Yoon Hong Man , An Ji Yeong , Eom Bang Wool , Hur Hoon , Lee Young-Joon , Cho Gyu Seok , Park Youngkyu , Jung Mi Ran , Park Ji-Ho , Hyung Woo Jin , Jeong Sang-Ho , Nam Byung-Ho 
Published: September 2018

4028 Background: The benefits and hazards of laparoscopic sentinel node oriented stomach-preserving surgery, compared to those of laparoscopic standard gastrectomy with lymph node dissection in early gastric cancer (EGC), are unknown. The SENORITA trial investigated the clinical impact of laparoscopic sentinel node oriented stomach-preserving surgery in EGC. Methods: Other than those with absolute indication for endoscopic resection, eligible patients had EGC confined to the mucosa and submucosa, with diameter ≤ 3cm, regardless of histology on preoperative evaluation. Patients were randomized for laparoscopic standard gastrectomy or laparoscopic stomach-preserving surgery. Patients were stratified based on depth (mucosa vs. submucosa) and size (≤ 2cm vs. 2 < ≤ 3cm) of the EGC and by participating institution. The primary endpoint was 3-year disease-free survival (3yDFS). The expected 3yDFS was 97% and non-inferior margin was 5%. 580 patients and 24 events were needed to show non-inferiority with 80% power. One interim analysis was planned after 12 events (50%) occurred. Using the O’Brien-Fleming error spending function, the two-sided nominal significance level for the interim analysis would be 0.0054. Results: From March 2013 to May 2016 462 patients were randomized; analysis was performed in 421 after a dropout of 41 patients. Laparoscopic stomach-preserving surgery was possible in 75.6% by study protocol. Interim analysis was conducted based on 12 events (median follow-up: 15.89 months). The 3yDFS in the laparoscopic standard gastrectomy arm was 96%; the 3yDFS in the laparoscopic stomach-preserving surgery arm was 93%, (99.46% CI: -3.18%, 9.18%). The postoperative complication rates were 15.0% and 12.9%, respectively (p = 0.542). Conclusions: In this interim analysis, laparoscopic sentinel node oriented stomach-preserving surgery did not show non-inferiority for 3yDFS. The follow-up time was not mature enough to evaluate non-inferiority. Further follow-up will elucidate the role of laparoscopic sentinel node oriented stomach-preserving surgery. Clinical trial information: NCT01804998.
Exclusive chemoradiotherapy with or without dose escalation in locally advanced esophageal carcinoma: The CONCORDE study (PRODIGE 26).
Authors: Crehange Gilles , Bertaut Aurelie , Peiffert Didier , Le Prise Elisabeth , Etienne Pierre-Luc , Rio Emmanuel , Pereira Renata , Noel Georges , Benezery Karen , Bonnetain Franck , Seitz Jean Francois 
Published: September 2018

4037 Background: In esophageal cancer (EC), 20 to 45% of patients suffer from local failure after 50Gy concomitant chemoradiation (cCRT). Improvements in staging together with target definitions led us to test dose escalation in the modern era of new technologies. Methods: Patients were randomly assigned cCRT to 40Gy elective nodal irradiation with either a 10Gy boost (Arm A) or 26Gy boost (Arm B) combined with FOLFOX-4. The primary endpoint of this phase II was acute toxicity according to the NCIC-CTCAE (version 4.0). Quality of life according to the EORTC QLQ-C30 and OG25 was a secondary endpoint. All analyses were performed in intent-to-treat. Results: 160 patients were randomized between Jun 2011 and Feb 2016: 81 patients in arm A and 79 patients in arm B. The mean age at diagnosis was 61.9 (7.9) years and 62.1 (7.8) years, respectively. Seventy patients in each arm had squamous cell carcinoma (86.4% in arm A and 88.6% in arm B) and 59 patients (72.8%) and 58 patients (73.4%) had stage III disease in arms A and B, respectively. IMRT was performed in 57 (70.4%) and 55 (69.6%) patients in arms A and B. The rates of grade ≥3 (G3+) non-hematological toxicity were not significantly different between arms A and B (76.5% vs 86.0%, p = 0.12). The rates of G3+ hematological toxicity were not significantly different between arms A and B (82.7% vs 88.6%, p = 0.29). The rates of G3+ non-hematological toxicity were not significantly different between patients treated with 3DRT (83.3%) and IMRT (81.3%) (p = 0.77). The mean global health scores at baseline and 3 months were 63.9 (sd = 21.4) vs 69.6 (sd = 23.1) in arm A (p = 0.10) and 65.27 (sd = 19.54) vs 58.8 (sd = 19.9) in arm B (p = 0.16). The presence of dysphagia was neither significantly different between arm A (89.23%) and arm B (86.21%) (p = 0.61) at baseline nor at 3 months (77.78% vs 86.84%, p = 0.29). Odynophagia was present at baseline in 78.46% in arm A and 75.86% in arm B (p = 0.73) while the rates observed at 3 months were 68.18% and 73.68%, respectively (p = 0.59). Conclusions: Dose escalated cCRT in patients with EC is feasible with no increased acute toxicity and no deterioration of QOL. A phase III trial is on-going to conclusively address the issue of local control with cCRT. Clinical trial information: NCT01348217.
The Nationwide Cancer Genome Screening Project in Japan SCRUM-Japan, GI-screen: Efficient identification of cancer genome alterations in advanced gastric cancer.
Authors: Kadowaki Shigenori , Shitara Kohei , Yuki Satoshi , Hironaka Shuichi , Kato Takeshi , Hara Hiroki , Kajiwara Takeshi , Izawa Naoki , Iwasa Satoru , Moriwaki Toshikazu , Naruge Daisuke , Esaki Taito , Saeki Hiroshi , Kudo Toshihiro , Cho Haruhiko , Tamura Takao , Ebi Hiromichi , Nomura Shogo , Ohtsu Atsushi , Yoshino Takayuki 
Published: September 2018

4041 Background: We have conducted the Nationwide Cancer Genome Screening Project in Japan since April 2015 using Next Generation Sequencing in advanced non-colorectal gastrointestinal (GI) cancer (aNon-CRC), called as the SCRUM-Japan GI-SCREEN. Methods: This study is ongoing with 20 major cancer centers. Patients with aNon-CRC, who plan to or receive chemotherapy were eligible. DNA and RNA were extracted from FFPE tumor samples and were analyzed by the Oncomine Cancer Research Panel (OCP) which allows to detect gene mutation, copy number variant (CNV) and fusions across 143 genes in a CLIA certified CAP accredited laboratory. The detected genomic variant data were classified according to whether genetic drivers of cancer including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase. In this presentation, we show the results of advanced gastric cancer (aGC) cohort. Results: As of October 31st in 2016, a total of 565 aGC samples were analyzed. The sequence with the OCP was successfully performed in 425 (75.2%). Out of 475 patients except for the 90 patients in which precise data is not collected, the proportion of histology type is followed; intestinal type 44.6%, diffuse type 54.5%, other 0.6%, unknown 0.2%. Out of 406 samples of which results were available, the frequently detected mutations were TP53 (47.8%), PIK3CA (8.6%), KRAS (5.4%), SMAD4 (4.9%), TET2 (4.4%), APC (3.9%), ERBB2 (3.7%) and CNVs were ERBB2 (10.8%), CCNE1 (9.4%), KRAS (3.7%), ZNF217 (3.2%), FGFR2 (2.7%), and MET (2.5%). FGFR3-TACC3 fusion, WIPF2- ERBB2 fusion and EGFR vIII were detected in 2, 1, and 2 cases, respectively. Conclusions: This nationwide screening system is efficient to detect rare gene alterations in aGC. This novel knowledge provides an intriguing background to investigate new target approaches and represents a progress toward more precision medicine. Clinical trial information: UMIN000016344.
Is surgical resection beneficial in recurrent or metastatic gastric cancer?
Authors: Choi Yong Won , Ann Mi Sun , Lee Hyun Woo , Kang Seok Yun , Choi Jin-Hyuk 
Published: September 2018

4043 Background: Although chemotherapy is currently established as a standard treatment in recurrent or metastatic gastric cancer, the role of palliative surgical resection is still controversial. We investigated the survival benefit of surgical resection in patients (pts) with recurrent or metastatic gastric cancer who received systemic chemotherapy. Methods: A retrospective review was conducted on 698 pts who received palliative chemotherapy for recurrent (n = 307) or primary metastatic (n = 391) gastric cancer. Overall survival (OS) of pts who underwent surgical resection followed by chemotherapy was compared to that of pts who received chemotherapy alone. Results: Among 140 pts (primary metastatic: 97, recurrent: 43) with surgical resection, gastrectomy, metastasectomy, and gastrectomy with metastasectomy were performed in 83 (primary metastatic: 81), 44, and 13 pts, respectively. Higher surgical resection rate was observed in pts with young age ( < 70) (p = 0.010), ECOG PS 0 or 1 (p = 0.010), primary metastatic (p < 0.0001), absence of liver metastasis (p = 0.002), and signet ring cell histology (p = 0.002). The median OS of pts who underwent surgical resection before chemotherapy was significantly longer than that of pts who received chemotherapy alone (19 vs. 9 months, p <0.0001). The OS benefit of surgical resection was consistent across subgroups in terms of baseline characteristics including age, ECOG PS, disease status (primary metastatic vs. recurrent), peritoneal metastasis, and first-line chemotherapy regimen (single vs. combination). In multivariate analysis, surgical resection was independently associated with favorable OS (hazard ratio = 0.41, p < 0.0001) along with ≥second-line chemotherapy (p < 0.0001), whereas ECOG PS 2 or 3 (p = 0.013), signet ring cell histology (p < 0.0001), and peritoneal metastasis (p = 0.046) were independent prognostic factors of poor OS. Conclusions: The present study suggests that judicious use of surgical resection before chemotherapy in recurrent or metastatic gastric cancer pts may result in favorable outcome, although large scale phase III trials are essential to establish this treatment approach as a standard practice.
Nomogram for lymph node metastasis prediction with early gastric cancer patients: To decide additional gastrectomy after endoscopic dissection.
Authors: Kim Su Mi , Min Byung-Hoon , An Ji Yeong , Choi Min-Gew , Ryu Keun Won , Kim Young Woo , Jung Sin-Ho , Sohn Tae Sung , Bae Jae-Moon , Kim Sung , Kim Jae J. , Lee Jun Ho 
Published: September 2018

4045 Background: Accurate prediction of metastatic lymph node is critical to avoid unnecessary gastrectomy and improve quality of life for patients with early gastric cancer. The aim of this study was to develop and validate a nomogram for prediction of lymph node metastasis in early gastric cancer patients. Methods: We reviewed the clinicopathological data of 10595 patients who underwent curative resection for early gastric cancer from 2001 to 2015 at Samsung Medical Center. This model was externally validated by 2100 patients who underwent curative resection for gastric cancer in National Cancer Center. Multivariate analysis using the Cox proportional hazard regression model was performed to develop the nomogram, and discrimination and calibration were evaluated by external validation. Overall survival, disease free survival, and recurrence free survival were compared between gastrectomy groups of 6641 patients and endoscopic dissection group of 999 patients who was performed the treatment in Samsung Medical Center for early gastric cancer by risk on nomogram to demonstrate the efficacy of nomogram. Results: Multivariate analyses revealed that age, tumor size, lymphatic invasion, depth of invasion, and histologic differentiation were significant prognostic factors for lymph node metastasis. The nomogram had good discrimination with a concordance index of 0.845 [95% confidence interval 0.832-0.858], supported by an external validation point of 0.813[95% confidence interval 0.786-0.84]. In low risk on nomogram, endoscopic dissection group had similar overall survival (P = 0.319), disease free survival (P = 0.469) and recurrence free survival (P = 0.091) compared to gastrectomy group. Conclusions: We developed and validated a nomogram predicting lymph node metastasis for early gastric cancer based on a large database. This personalized nomogram is useful to avoid unnecessary gastrectomy after endoscopic dissection resulting in improved quality of life for early gastric cancer patients.
A phase II study (KSCC/HGCSG/CCOG/PerSeUS1501B) of trastuzumab plus S-1 and oxaliplatin for HER2-positive advanced gastric cancer.
Authors: Shinozaki Katsunori , Yuki Satoshi , Kashiwada Tomomi , Kusumoto Tetsuya , Iwatsuki Masaaki , Satake Hironaga , Kobayashi Kazuma , Esaki Taito , Nakashima Yuichiro , Kubo Nobuhide , Tokunaga Shoji , Shimose Takayuki , Makiyama Akitaka , Saeki Hiroshi , Oki Eiji , Baba Hideo , Maehara Yoshihiko 
Published: September 2018

4059 Background: A combination of S-1 and cisplatin (SP) has been the standard regimen for advanced gastric cancer (AGC) in East Asia. The combination of S-1 and oxaliplatin (SOX100) was demonstrated to be non-inferior to SP in the randomized phase III study. The ToGA study demonstrated that trastuzumab (T-mab) combination therapies with cisplatin and fluoropyrimidines improved the overall survival of patients with HER2-positive AGC. This multicenter study is the first phase II trial to assess the efficacy and safety of T-mab in combination with S-1 and oxaliplatin (HER-SOX130) in HER2-positive AGC. Methods: Patients with HER2-positive AGC or recurrent gastric cancer defined to be IHC 3+ or IHC 2+/FISH positive received 80 mg/m2 S-1 per day orally on days 1–14, 130 mg/m2 oxaliplatin intravenously on day 1, and T-mab (8-mg/kg loading dose and 6 mg/kg thereafter) intravenously on day 1 of a 21-day cycle until one of the criteria for withdrawal of the study treatment occurred. The primary end-point was the response rate (RR). Adverse events were recorded based on the NCI-CTCAE Vers.4.0. The threshold response rate was defined as 50%, and the expected rate was set at 70%, with an 80% power and a 1-sided alpha value of 0.05. The calculated sample size was 37 patients. Results: For this study, 42 patients (median age, 66 years) were enrolled from June 2015 to May 2016. Three patients were excluded owing to ineligibility. Efficacy and safety analyses were conducted in the full analysis set of 39 patients. The proportion of patients with IHC 3+ was 87%. The confirmed RR assessed by the independent review committee was 82.1(32/39) % (95% confidence interval [CI]: 67.3–91.0), and the disease control rate was 87.2(34/39) % (95% CI: 73.3–94.4). The incidence rates of grade 3 or 4 adverse events were as follows: neutropenia, 12.8%; thrombocytopenia, 17.9%; anemia, 10.3%; sensory neuropathy, 5.1%; anorexia, 17.9%; diarrhea, 7.7%; and teary eyes, 2.6%. Conclusions: HER-SOX130 demonstrated encouraging efficacy with a favorable safety profile. The survival benefit of this regimen needs to be validated by conducting further follow-up of patients. Clinical trial information: 000017552.
Safety and activity of the pan-fibroblast growth factor receptor (FGFR) inhibitor erdafitinib in phase 1 study patients (Pts) with molecularly selected advanced cholangiocarcinoma (CCA).
Authors: Soria Jean-Charles , Strickler John H. , Govindan Ramaswamy , Chai Seungjean , Chan Nancy , Quiroga-Garcia Vanesa , Bahleda Rastislav , Hierro Cinta , Zhong Bob , Gonzalez Martha , Santiago-Walker Ademi E. , Parekh Trilok V. , Luo Feng Roger , Sullivan-Chang Loretta , Xie Hong , Tabernero Josep 
Published: September 2018

4074 Background: Erdafitinib (JNJ-42756493) is a potent, oral pan-FGFR tyrosine kinase inhibitor that demonstrated encouraging preliminary clinical activity and manageable adverse events (AEs) in its first-in-human phase 1 study in advanced solid tumors (NCT01703481). Here we report results from pts with CCA from this study. Methods: This 4-part study enrolled pts age ≥ 18 years (y) with advanced solid tumors. Dose escalation (part 1) followed a 3+3 design, with pts receiving ascending doses of erdafitinib continuously or intermittently (7 days on/7 days off). Subsequent parts required FGFR gene alterations in the tumor, including activating mutations and translocations or other FGFR-activating aberrations. Part 2 was a pharmacodynamics cohort. Parts 3 and 4 were dose-expansion cohorts for recommended phase 2 doses of 9 mg once daily (QD) and 10 mg intermittently, respectively. Results: Eleven pts with FGFR-aberrant CCA were treated at 9 mg QD (n = 1) or 10 mg intermittent (n = 10). Median age was 60 y; 7 of 11 pts were female (64%). 73% of pts had ECOG performance status 1. All had prior systemic therapy. Median treatment duration with erdafitinib was 5.3 months (mo). Systemic erdafitinib exposure, per Cmax and AUC, in CCA pts was similar to other indications. The most common AEs were stomatitis (82%), hyperphosphatemia (64%), dry mouth (55%), dysgeusia (45%), dry skin (45%), and asthenia (45%), mostly grade 1/2 severity. No drug-related grade ≥3 AEs were reported in > 1 pt except grade 3 stomatitis (n = 2; 18%). The objective response rate, all confirmed partial responses (PRs) per RECIST 1.1, was 27.3% (3/11; 95% CI 6, 61); an additional 27.3% (3/11) had stable disease as their best response. Overall disease control rate was 55%. All 3 PRs were at the 10 mg intermittent dosage, and the median duration of response was 12.9 mo. With a median follow-up of 5.1 mo, median progression-free survival was 5.1 mo (95% CI 1.6, 16.4). As of the cutoff date, 2 pts continue on study treatment. Conclusions: Erdafitinib showed encouraging clinical activity and minimal toxicity in pts with advanced CCA and FGFR alterations. These results warrant further study. Clinical trial information: NCT01703481.
Pharmacokinetic/pharmacodynamic (PK/PD) profile of AG-120 in patients with IDH1-mutant cholangiocarcinoma from a phase 1 study of advanced solid tumors.
Authors: Fan Bin , Goyal Lipika , Lowery Maeve Aine , Pandya Shuchi Sumant , Manyak Erika , Le Kha , Jiang Liewen , Auer Julia , Dai David 
Published: September 2018

4082 Background: Somatic mutations in isocitrate dehydrogenase 1 (IDH1) produce the oncometabolite D-2-hydroxyglutarate (2-HG). AG-120 is a first-in-class selective inhibitor of mutant IDH1 (mIDH1) under evaluation in an ongoing phase 1 study in patients with mIDH1 advanced solid tumors, including cholangiocarcinoma (CC) (NCT02073994). Objectives for this abstract were to 1) characterize the PK profile of AG-120 and the relationship between AG-120 exposure and 2-HG suppression, and 2) evaluate the influence of intrinsic patient factors on AG-120 clearance, in patients with mIDH1 CC. Methods: AG-120 was administered orally once daily (QD) or twice daily (BID) in continuous 28-day cycles. As of Dec 5, 2016, 60 of 73 patients enrolled with mIDH1 CC had PK/PD samples available for analysis at 100 mg BID, 300 mg QD, 400 mg QD, 500 mg QD, 800 mg QD, and 1200 mg QD in dose escalation (n = 24) and 500 mg QD (n = 36) in dose expansion. Blood (n = 60) and fresh tumor biopsy samples (n = 14) were collected to assess AG-120 and 2-HG using qualified liquid chromatography-tandem mass spectrometry methods. Results: Following both single and multiple doses, AG-120 plasma exposure increased less than dose proportionally from 100 to 1200 mg. Mean terminal half-life was 38.4–85.8 h, supporting a QD dosing regimen. Following multiple doses, steady state was reached within 15 days, with approximately 2-fold accumulation in plasma AG-120 exposure. No patient-specific factors were identified as clinically significant covariates affecting AG-120 plasma clearance. After multiple doses, plasma 2-HG levels were reduced (up to 98.4% inhibition, achieving levels similar to those in healthy volunteers) and tumor biopsy 2-HG levels were also substantially reduced (by up to 99.9%) at all dose levels tested. The 500 mg QD dose resulted in the largest magnitude of 2-HG inhibition vs. other dose levels. Conclusions: AG-120 demonstrated a long half-life in patients with mIDH1 CC and robustly inhibited 2-HG in plasma and tumor samples. These PK/PD data, along with emerging safety and clinical activity data, support the selection of 500 mg QD for future clinical investigation. Clinical trial information: NCT02073994.