bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Gastroplegia Patch on treating postoperative gastroplegia: A multicenter, double-blind, randomized controlled trial.
Authors: Zhou Tian , Zhou Qin , Wang Yanbin , Ye Yingjiang , Tian Yantao , Hu Kaiwen 
Published: September 2018

10110 Background: Postoperative gastroplegia is common in digestive cancer patients and there were no effective treatments. Gastroplegia Patch is an external-used Chinese Herbal Medicine recipe. It has been applied clinically for more than ten years, which showed good effect. We conducted this study to verify its safety and efficacy on the symptoms of postoperative gastroplegia. Methods: This clinical trial was designed as a multi-center, double-blind, superior effect, randomized controlled trial. It has been registered in ISRCTN (No.18291857) before initiation and was monitored by the third party. Patient inclusion criteria: 1. Gastroenterological cancer patient who was diagnosed as post-surgery gastroplegia, could not eat and need tube feeding (parenteral nutrition or with Jejunum nutrient canal); 2. The local identification of abdomen is cold pattern, which means this kind of patient prefers heat to cold, likes hot food and hates cold ones. Eligible participants were randomized into two arms, placebo arm and Patch arm, respectively. Beside the basic treatments (nutrition support, gastrointestinal decompression, promoting gastric dynamics medicine), placebo or Gastroplegia Patch was applied in control group or Patch group, respectively. Placebos or the patches were allocated at two acupuncture points ( Zhongwan and Shenque). The intervention course was 14 days or reached primary endpoint. The primary endpoint was able to eat without tube feeding. Results: All the 120 eligible participants (60 per arm) were recruited from four AAA hospitals in Beijing, China. Analysis was conducted based on intent-to-treat strategy. After the intervention, 68.33% of the participants in the Patch group were able to eat without tube feeding, which significantly higher than that of 41.67% in the control group (p = 0.003). It took 8 days on average in the Patch group to show effect, which significantly faster than that of 10 days in the control group (p = 0.017). The incidences of adverse events were compatible between the two arms (p = 0.244). Conclusions: Gastroplegia Patch is safe and effective in treating postoperative gastroplegia in gastroenterological cancer patients with cold syndrome. Clinical trial information: 18291857.
Safety and efficacy of alternating treatment with EP2006, a filgrastim biosimilar, and reference filgrastim for the prevention of severe neutropenia, in patients with breast cancer receiving myelosuppressive chemotherapy.
Authors: Krendyukov Andriy , Harbeck Nadia , Gascon Pedro , Gattu Sreekanth , Li Yuhan , Blackwell Kimberly L. 
Published: September 2018

10116 Background: In 2015, filgrastim EP2006 (Zarxio) became the first biosimilar approved by the FDA for commercial use in the US. This phase III randomized, double-blind registration study in patients with breast cancer receiving (neo)adjuvant myelosuppressive chemotherapy (TAC) compares US-licensed filgrastim, Neupogen (reference), with two groups who received alternating treatment with reference and biosimilar every other treatment cycle. Methods: A total of 218 patients receiving 5µg/kg/day filgrastim over 6 chemotherapy cycles were randomized 1:1:1:1 into 4 arms. Two arms received only 1 product, biosimilar or reference (unswitched), and 2 arms (switched) received alternating treatments every other cycle (biosimilar then reference or vice versa over cycles 1─6). Since the switch occurred from Cycle 2 onwards, this analysis compared pooled switched groups to the unswitched reference group for efficacy during Cycles 2─6. Safety was also assessed. Non-inferiority in febrile neutropenia (FN) rates between groups for Cycles 2─6 was shown if 95% confidence intervals (CIs) were within a pre-defined margin of -15%. Results: A total of107 patients switched treatment, and 51 patients received reference in all cycles. Baseline characteristics were similar between groups. Incidence of FN was 3.4% (switched) vs. 0% (reference) (95% CI: -9.65; 4.96), which is within the predefined non-inferiority margins. Infections occurred in 9.3% (switched) vs. 9.9% (reference). Hospitalization due to FN was low with 1 patient in Cycle 6 (switched). TEAEs related to filgrastim were reported in 42.1% (switched) vs. 39.2% (reference) (all cycles). Musculoskeletal/connective tissue disorders related to filgrastim occurred in 35.5% (switched) vs. 39.2% (reference) (all cycles), including bone pain (30.8% vs. 33.3%). No anti-drug antibodies were identified. Conclusions: There was no evidence of clinically meaningful differences when patients with breast cancer were switched from reference to biosimilar filgrastim, or from biosimilar to reference filgrastim. Clinical trial information: NCT01519700.
Frequency and factors predictive of aberrant drug behavior in patients presenting to outpatient supportive care center at a comprehensive cancer center.
Authors: Yennu Sriram , Edwards Tonya , Arthur Joseph Anthony , Williams Janet L. , Lu Zhanni , Reddy Suresh , Bruera Eduardo 
Published: September 2018

10118 Background: Opioid misuse is a growing crisis in cancer patients. Cancer patients at risk of aberrant drug behaviors (ADB) are frequently underdiagnosed in routine cancer care. The aim of this study was to determine the frequency and factors associated with ADB using the “Screener and Opioid Assessment for Patients tool” (SOAPP-14) in cancer patients seen at the outpatient supportive care center. We also examined the screening performance of Cut Down, Annoyed, Guilty, and Eye Opener (CAGE-AID) as compared to The SOAPP-14 as a gold standard. Methods: In this retrospective study, 1108 consecutive patients referred to supportive care clinic were reviewed. Patients were eligible if they were ≥18 yrs, have a diagnosis of cancer, and were on opioids for pain for atleast a week. Patients’ demographics, the Edmonton Symptom Assessment Scale (ESAS), SOAPP-14, and CAGE-AID scores were analyzed. ADB+ was defined as SOAPP-14 score ≥7. Descriptive statistics, spearman correlation coefficient, multivariate, and ROC analysis were performed. Results: 703/1108 consults were eligible. A total of 153/703 (22%) were ADB +ve. SOAPP-14 scores were positively correlated with CAGE-AID r = .38, p < 0.001; male gender r = 0.11, p = 0.003; ESAS pain r = 0.11, p = 0.005; ESAS depression r = 0.22, p < 0.001; ESAS anxiety r = 0.22, p < 0.001, and ESAS financial distress r = 0.23, p < 0.001. Multivariate analysis indicated that the odds ratio for ADB +ve was 6.18 in patients with CAGE-AID+ (p < 0.001), 1.8 for male gender (p = 0.007), 1.1/pt. for ESAS anxiety (p = 0.044), and 1.1/pt. for ESAS financial distress (p = 0.007). A CAGE-AID score of 1/4 has a sensitivity of 47%, specificity of 89% positive predictive value 63.6% and negative predictive value 69.2%. Conclusions: Our study suggests that 22% of cancer patients on opioids presenting to supportive care center are at risk of aberrant drug behavior (ADB). Male patients with anxiety, financial distress, and prior alcoholism/illicit drug use are significant predictors of ADB’s. A cut off score of ≥1 out 4 on CAGE-AID questionnaire allows better screening of ADB in outpatient advanced cancer patients. Further research to effectively manage these patients is needed.
Radiation for bone metastases: Reconsidering the optimal timing.
Authors: Yang Joanna C. , Hsu Brittany , Wu Abraham Jing-Ching , Kohutek Zachary , Yang T. Jonathan 
Published: September 2018

10122 Background: Bone metastases impair function and decrease quality of life due to acute or chronic pain. The standard approach for patients with multiple bone metastases is systemic therapy and palliative radiation therapy (RT) when the metastases become symptomatic. This study aims to understand the characteristics and outcomes for inpatients admitted for painful bone metastases. Methods: An inpatient radiation oncology consult registry was created in 2015 to evaluate patterns of care for patients receiving RT in the inpatient setting. Of the 1151 consults requested between 7/2015 and 6/2016, 28% (n = 323) were for evaluation of symptomatic bone metastases in patients who were hospitalized for acute or chronic pain. Among this cohort, 64% (n = 208) went on to receive RT for 225 bone metastases. Sixty percent of RT courses were initiated while the patient was hospitalized. Clinical characteristics correlated with overall survival (OS) were evaluated through Cox regression analysis. Results: The median follow up for the 208 patients who received RT was 4 months (0.1-9 months). Patient median age was 61 (10-92 years), and the median KPS was 70 (20-90). The most common sites treated were spine (50%), joints such as hip and shoulder (11%), long bones including femur and humerus (11%), and pelvis (10%). Sixty-one percent (n = 138) of the treated metastases were diagnosed ≥4 months prior to RT. The median survival after receiving palliative RT was 4 months (0-19 months). Among the 141 patients who had died at the time of analysis, 92 (65%) died within 2 months, and 128 (91%) within 6 months. Eighteen patients (9%) discontinued RT to transition to hospice care. OS after RT is significantly correlated with KPS (p < 0.0001) at the time of consult but not with patient age or site of treated disease. Conclusions: In this select group of inpatients who were evaluated for palliation of symptomatic bone metastases, we found a short OS after RT. The majority of metastases were present for ≥4 months prior to RT. This study suggests that earlier RT for high-risk metastases should be considered to prevent development of symptomatic disease that requires hospitalization. Risk factors for development of painful bone metastases are being studied prospectively at our institution.
Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA (ctDNA) in metastatic breast cancer.
Authors: Fribbens Charlotte Victoria , Garcia-Murillas Isaac , Beaney Matthew , Hrebien Sarah , Howarth Karen , Epstein Michael , Rosenfeld Nitzan , Ring Alistair E. , Johnston Stephen R. D. , Turner Nicholas C. 
Published: September 2018

1015 Background: Selection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have a high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to first line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer. Methods: Seventy-one patients on first line AI therapy for metastatic breast cancer were enrolled in a prospective study to collect plasma samples for ctDNA analysis every three months on therapy, and at disease progression. All plasma samples were analysed with ESR1 multiplex digital PCR assays, and samples at disease progression were analysed by InVision (enhanced tagged-amplicon sequencing). Mutations were tracked back through samples prior to disease progression to study the evolution of mutations on therapy. Results: Of the 34 patients who progressed on first line AI, 53% (18/34) had ESR1 mutations detectable at progression. Sequencing of progression plasma ctDNA identified polyclonal RAS mutations in 10.7% (3/28) progressing patients (2 polyclonal KRAS, 1 monoclonal HRAS), all of whom also had ESR1 mutations, and a patient with an activating p.R248C FGFR3 mutation. ESR1 mutations were subclonal in 78.6% (11/14) patients, with all RAS mutations being rare subclones. In serial tracking prior to progression, ESR1 mutations were detectable in plasma with a median of 5.3 months (95% CI 2.9-NA) prior to clinical progression. Conclusions: ESR1 mutations are found at high frequency in patients progressing on AI, but are frequently sub-clonal and may not be the sole driver of AI resistance in these patients. Poly-clonal KRAS mutations are identified as a novel mechanism of resistance to AI, associated with detection of ESR1 mutations.
Efficacy of trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (MBC) previously treated with pertuzumab (P).
Authors: Urruticoechea Ander , Im Seock-Ah , Munoz Montserrat , Baselga Jose , Yardley Denise A. , Heeson Sarah , Jones Sarah , Knott Adam , Douthwaite Hannah , Badovinac Crnjevic Tanja , Swain Sandra M. 
Published: September 2018

1023 Background: T-DM1 was approved for pts with HER2+ MBC previously treated with trastuzumab (H) and a taxane based on the phase III EMILIA study. P in combination with H + docetaxel (T) later became the first-line standard of care for HER2+ MBC, but there are limited data on T-DM1 efficacy in pts who previously received P. We present exploratory efficacy results from pts treated with T-DM1 any time after P from 2 phase III studies: CLEOPATRA and PHEREXA. Methods: CLEOPATRA (NCT00567190) and PHEREXA (NCT01026142) are randomized, 2-arm trials evaluating P-based regimens for HER2+ MBC. CLEOPATRA studies H + T + P vs HT + placebo in pts with no prior anti-HER2 treatment (tx) or chemotherapy for MBC, while PHEREXA studies H + capecitabine (C) +/− P in pts who progressed during/after previous H tx for MBC. We assessed overall survival (OS) in an exploratory analysis of pts who either received or did not receive T-DM1 at any time after discontinuing study-assigned tx in CLEOPATRA or PHEREXA. Results: Of 408 pts who received HTP in CLEOPATRA and 228 pts who received HCP in PHEREXA, 32 and 43 pts received subsequent T-DM1, respectively (Table). Median duration of T-DM1 tx was 7.1 mo (range 0−44) and 4.2 mo (range 0−22), respectively, and median time from discontinuation of P to start of T-DM1 was 3.5 mo (range 1−47) and 10.6 mo (range 1−28). Conclusions: Although data are limited in these exploratory analyses, our results provide additional evidence of T-DM1 clinical activity in pts with HER2+ MBC who progressed on prior P + H, a finding with real-world implications. Clinical trial information: NCT00567190, NCT01026142. [Table: see text]
Eribulin in combination with pertuzumab plus trastuzumab for HER2-positive advanced or recurrent breast cancer (JBCRG-M03).
Authors: Narui Kazutaka , Yamashita Toshinari , Kitada Masahiro , Kawaguchi Hidetoshi , Hattori Masaya , Yoshinami Tetsuhiro , Matsunami Nobuki , Yanagihara Kazuhiro , Kawasoe Teru , Nagashima Takeshi , Bando Hiroko , Yano Hiroshi , Hasegawa Yoshie , Nakamura Rikiya , Kashiwaba Masahiro , Masuda Norikazu , Morita Satoshi , Ohno Shinji , Toi Masakazu ,   Japan Breast Cancer Research Group (JBCRG)
Published: September 2018

1025 Background: Pertuzumab (P) provided overall and progression-free survival (PFS) benefits in HER2-positive metastatic breast cancer (MBC) in the CLEOPATRA study as a first-line therapy. However, long-term administration of intravenous docetaxel at a dose of 75 mg/m2 every 3 weeks in MBC patients is difficult. Eribulin (E) is a well-tolerated cytotoxic agent. We report the efficacy and safety of E in combination with trastuzumab (T) plus P as first- and second-line therapy for metastatic or advanced BC in a multicenter, open-label phase II study (UMIN000012232). Methods: HER2-positive advanced or recurrent BC patients with no or a single prior therapy as advanced or recurrent chemotherapy were enrolled. All patients were administered T and taxane as adjuvant or first-line chemotherapy. Treatment consisted of E 1.4 mg/m2 on days 1 and 8 of a 21-day cycle and T (8 mg/kg loading dose > 6 mg/kg) plus P (840 mg loading dose > 420 mg) once every 3 weeks, all given intravenously. The primary end point was PFS. Results: From November 2013 to April 2016, 50 patients were enrolled. Forty-nine patients were eligible for safety analysis; full analysis set (FAS) includes 46 patients. The median patient age was 56 years (range 23–70), and 8 (16%) and 41 (84%) patients were treated in first- and second-line settings, respectively. Twenty-eight patients out of 49 patients (57%) continued the protocol therapy at the end of 8 cycles and median PFS was not yet reached. The response rate by RECIST ver.1.1 was 56.5% in FAS. The relative dose intensity of E, T, and P were 93.3% (range 77.0%–100%), 100% (range 96.0%–100%) and 100% (range 89.7%–100%), respectively in FAS. The grade 3/4 adverse effects (AE) were neutropenia in 5 patients (10.2%) including 2 patients (4.1%) with febrile neutropenia, hypertension in 3 patients (6.1%), and other AEs in only one patient. Average of the ejection fraction did not decrease significantly. Symptomatic left ventricular systolic dysfunction was not observed. Conclusions: E in combination with T plus P was well-tolerated and could be an alternative to docetaxel-based combination therapy for HER2-positive MBC. Clinical trial information: 000012232.
Palbociclib (PAL) + letrozole (L) as first-line (1L) therapy (tx) in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC): Efficacy and safety across patient (pt) subgroups.
Authors: Finn Richard S. , Dieras Veronique , Rugo Hope S. , Joy Anil A. , Moulder Stacy L. , Walshe Janice Maria , Mukai Hirofumi , Shparyk Yaroslav V. , Park In Hae , Mori Ave , Lu Dongrui (Ray) , Gauthier Eric Roland , Gelmon Karen A. 
Published: September 2018

1039 Background: Hormone tx (HT) is the primary 1L tx for ER+ ABC. In the PALOMA-2 study (NCT01740427), PAL+L as 1L ABC tx prolonged progression-free survival (PFS; hazard ratio [HR] 0.58; P<.001) (Finn et al, NEJM. 2016). Methods: Postmenopausal pts with ER+/HER2– ABC and no prior systemic treatment in the advanced setting were randomized 2:1 to PAL (125 mg/d oral [3 wk on, 1 wk off]) + L (2.5 mg QD) or placebo (P) + L. Key endpoints were investigator-assessed PFS and safety. Results: 666pts (444, PAL+L; 222, P+L) were enrolled. Pts were similarly distributed between arms for visceral (48%) and nonvisceral (52%) disease and prior HT (56%) and no prior HT (44%); more pts had disease-free interval (DFI) >12 mo (40%) than ≤12 mo (22%). Median PFS (mPFS) was improved in all subgroups by adding PAL to L (Table). Adverse events were consistent across subgroups, as described for the full study population. Conclusions: PAL+L improved mPFS vs P+L with manageable toxicity across all subgroups including those with visceral disease. PAL+L provides a 1L option that should be considered for all pts with ER+/HER2- ABC. Sponsor: Pfizer Clinical trial information: NCT01740427. [Table: see text]
Preliminary results of a phase I/IIa study of BMS-986156 (glucocorticoid-induced tumor necrosis factor receptor–related gene [GITR] agonist), alone and in combination with nivolumab in pts with advanced solid tumors.
Authors: Siu Lillian L. , Steeghs Neeltje , Meniawy Tarek , Joerger Markus , Spratlin Jennifer L. , Rottey Sylvie , Nagrial Adnan , Cooper Adam , Meier Roland , Guan Xiaowei , Phillips Penny , Bajaj Gaurav , Gokemeijer Jochem , Korman Alan J. , Aung Kyaw Lwin , Carlino Matteo S. 
Published: September 2018

104 Background: BMS-986156 is a fully human IgG1 agonist mAb that binds GITR and promotes T effector cell activation and possible reduction/inactivation of T regulatory cells. Preclinical data show enhanced antitumor T-cell activity with anti-GITR + anti–programmed death-1 (PD-1). Here we describe preliminary dose escalation data from a phase I/IIa study of BMS-986156 ± nivolumab (anti–PD-1 mAb) in pts with advanced solid tumors (NCT02598960). Methods: During dose escalation, pts received BMS-986156 (10–800 mg) or BMS-986156 (30–800 mg) + nivolumab (240 mg) every 2 weeks. Objectives included safety (primary), immunogenicity, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. Results: As of Dec 12, 2016, 66 pts were treated with BMS-986156 (n = 29) or BMS-986156 + nivolumab (n = 37).No dose-limiting toxicities (DLTs) were reported during dose escalation. The most common treatment-related adverse events reported with BMS-986156/BMS-986156 + nivolumab included pyrexia (21%/30%), chills (10%/16%), and fatigue (14%/14%); events were G1/2 in all pts except for 4 pts (6%) treated with the combination (G3 lipase [n = 1], G3 lung infection [n = 1], G3 fatigue [n = 1], and G3 aspartate aminotransferase with G4 creatine phosphokinase [n = 1; leading to discontinuation of treatment]). Preliminary data indicate that the incidence of immunogenicity to BMS-986156 was low when BMS-986156 ± nivolumab was administered. Preliminary data also indicate that BMS-986156 ± nivolumab exhibits linear PK with dose proportionality after a single dose, and BMS-986156 ± nivolumab is biologically active in PD analyses in peripheral blood. Initial antitumor activity has been observed in several pts treated with the combination; these data will be reported. Conclusions: This is the first report of clinical data with an anti-GITR mAb ± a PD-1 inhibitor.BMS-986156 ± nivolumab was well tolerated, with no DLTs and low immunogenicity. Antitumor activity was observed with BMS-986156 + nivolumab at doses predicted to be biologically active. Further evaluation of this combination in pts with advanced solid tumors is ongoing. Clinical trial information: NCT02598960.
Evaluation of tumor and circulating cell free (cf) DNA mutations in women with hormone refractory metastatic breast cancer (MBC) enrolled in a phase I study of Z-endoxifen (MC093C).
Authors: Goetz Matthew P. , Suman Vera J. , Reid Joel M. , Northfelt Donald W. , Burhow Sarah A , Safgren Stephanie L. , McGovern Renee M. , Dockter Travis J. , Haddad Tufia C. , Erlichman Charles , Adjei Alex A. , Visscher Daniel W. , Kipp Benjamin , Hawse John , Doroshow James H. , Collins Jerry M. , Streicher Howard , Ames Matthew M. , Ingle James N. , Liu Minetta C. 
Published: September 2018

1043 Background: In estrogen receptor (ER) positive MBC, mutations (e.g. ESR1), identified from tumor biopsies or cfDNA, confer resistance. The concordance between mutations observed in tumor and cfDNA and the implications for response to Z-endoxifen, a potent anti-estrogen, are unknown. Methods: We previously conducted a phase I trial of Z-endoxifen in endocrine refractory, ER positive MBC. Seven dose levels were considered ranging from 20 to 160 mg/day followed by expansion cohorts (EC) of 40, 80, and 100 mg/day. Pretreatment blood samples (all pts) and fresh tumor biopsies (EC) were collected prospectively. Tumor and cfDNA were evaluated by targeted NGS. Results: 41 pts (38 evaluable) were enrolled. Prior endocrine therapy included aromatase inhibitors (37/38, 97%), fulvestrant (22/38, 58%) and tamoxifen (26/38, 68%). Substantial endoxifen exposure without DLTs at doses above 80 mg/day led to a halt in dose escalation and opening of the EC. Overall clinical benefit (stable > 6 months [7 pts.] or partial response by RECIST criteria [3 pts.]) rate was 26.3% (95%CI: 13.4-43.1%). cfDNA was obtained from 36 pts and mutations were identified in 13 (36%) including ESR1 [ Y537N or D538G] (5), PIK3CA [ H1047R or E542K] (8), TP53 [ K132R, R248Q, R267Q, or H179Y] (4), AKT ( Q79K) (1), and KRAS ( G12D) (1). In 5 pts with cf ESR1 mutations, 4 had additional cfDNA mutations including PIK3CA (3), and TP53 (1). PFS was shorter in pts with cfDNA mutations relative to those without (median: 61 vs.132 days; log-rank p = 0.021). Discordance was observed between tumor and cfDNA mutations where 3/7 PIK3CA tumor mutations were detected by cfDNA, 1/2 TP53 tumor mutations were detected by cfDNA, and 0/1 AKT tumor mutations were detected by cfDNA. Conversely, 2 pts had cfDNA mutations (either ESR1, TP53 or AKT) undetected in tumor. Conclusions: The absence of cfDNA mutations in patients with endocrine resistant, MBC treated with Z-Endoxifen was associated with significantly longer PFS. Given the discordance between tumor and cfDNA sequence data, future studies must determine which approach maximizes prognosis and prediction of benefit for estrogen-targeted therapy. Clinical trial information: NCT01327781.