bluuebunny/crossref_metadata_2025_split huggingface dataset:
An intersectional investigation of race and sex on receipt of adjuvant chemotherapy in stage III colon cancer.
Authors: Dhahri Amina , Carballido Estrella M. , Felder Seth , Dineen Sean Patrick , Powers Benjamin D 
Published: February 2020

86 Background: Race and sex disparities exist for receipt of adjuvant chemotherapy (AC) for stage III colon cancer. However, most studies have not used an intersectional approach, which assesses the cumulative effects of different identities (e.g., Black women) instead of treating each as distinct, independent variables. Using this approach, we assessed the summative impact of these identities on receipt of AC for stage III colon cancer. Methods: The National Cancer Database was queried from 2004 to 2015 for patients who underwent surgery for stage III colon cancer and were healthy enough for AC. Receipt of AC was assessed chi-squared and multivariable logistic regression analyses. Results: 92,696 patients were identified. White patients had higher rates of care at community cancer centers. Black patients had higher rates of treatment at academic cancer programs (p < 0.001). Overall 83.5% received AC. Black males and females had higher rates of AC (86.5% and 86.2%, respectively) compared to White males and females (85.3% and 80.5%), respectively (p < 0.001). In adjusted analysis, Black males had the lowest odds of AC (OR 0.73), followed by Black females (OR 0.89) and White females (OR 0.91). When evaluated by age < 65 years and adjusting for potential confounders, Black men remained the least likely group to receive AC (OR 0.70). Black females had similar odds of receipt of AC (OR 0.99) and White females had increased odds (OR 1.22) relative to White males. Conclusions: Despite higher rates of treatment at academic centers, Black males and females had lower odds of receipt of AC after adjusting for confounders. Younger Black males persisted with the lowest odds of AC, although younger Black females had odds similar to younger White males. Additional research is necessary to identify drivers of these disparities and interventions to ameliorate them. [Table: see text]
How to improve toxicity evaluation in clinical trials? Testing new metrics from irinotecan or oxaliplatin-based treatments in metastatic colorectal cancer (mCRC): A pooled analysis from 2,349 patients in ARCAD database.
Authors: Tournigand Christophe , Lopes Guilherme , Olswold Curtis L. , Adams Richard , Zalcberg John Raymond , Van Cutsem Eric , Saltz Leonard B. , Goldberg Richard M. , Hurwitz Herbert , Bokemeyer Carsten , Fuchs Charles S. , Chibaudel Benoist , Grothey Axel , De Gramont Aimery , Shi Qian 
Published: February 2020

89 Background: Monitoring of adverse events (AE) is crucial in clinical trials. Maximum grade per patient (pt) is commonly used but better metrics are needed to aid describing and comparing AE profiles. Methods: We developed and evaluated 2 longitudinal AE summary metrics. 1) Onset time of max grade refers to whether a pt has max grade within pre-specified timeframes for an AE, e.g. onset can be defined as “early” (max grade before the 6th cy) or “late” (≥ 6th cy). 2) Adverse effect load (AEL) is a longitudinal score of worst grade possible excluding death over the entire treatment for an AE. Higher AEL means worst overall experience of AE. We applied these metrics to real trial data. Pts were from 6 mCRC trials included in ARCAD database and received Irinotecan-based (n = 1,119) or Oxaliplatin-based (n = 1,230) treatments that did not include biologicals. AEs were diarrhea, nausea/vomiting, neutropenia/leukopenia, and neuropathy. We used linear model to AEL and logistic model to the other metrics, adjusting for age, sex, and number of metastases. Results: For nausea/vomiting, pts in Oxali-based chemo showed a higher AEL compared to patients in Iri-based (mean (M) [standard deviation (SD)] = 0.04 [0.06] vs. 0.02 [0.04]; p < 0.001) even though less pts had gr ≥ 3 (10.4% vs. 16.2%, resp.; p < 0.001), suggesting a lower-grade but persistent nausea/vomiting for Oxali-based. Among pts with diarrhea max gr 2, pts in Iri-based had higher AEL than with Oxali-based (M [SD] = 0.11 [0.11] vs. 0.08 [0.09]; p = 0.008), indicating more persistent diarrhea for Iri-based trts even among pts with same max grade. For neutropenia/leukopenia, pts in Oxali-based trts experienced higher AEL (M [SD] = 0.09 [0.13] vs. 0.05 [0.11], p < 0.001), and more pts in Oxali-based trts had gr ≥ 3 (70.1% vs. 64.4%; p = 0.002), suggesting that pts in Oxali-based trts experienced worst overall and max grade neutropenia/leukopenia compared to pts in Iri-based. Conclusions: To improve toxicity assessment in clinical trials, AEL and onset time of max grade are new measures that describe the evolution of adverse events over time. Further validation is warranted.
DPYD gene polymorphisms in patients with gastrointestinal tumors receiving chemotherapy with 5-fluorouracil.
Authors: Kit Oleg Ivanovich , Vladimirova Liubov Yu , Timoshkina Natalya N. , Storozhakova Anna E. , Petrusenko Natalia A. , Gvaldin Dmitry Yu. , Kabanov Sergey N. , Ryadinskaya Ludmila A. , Tikhanovskaya Natalia M. , Popova Irina L. , Abramova Natalia A. , Samaneva Natalia Yu. , Teplyakova Maria A. , Lyanova Aza A. , Novoselova Kristina A. , Kalabanova Elena Aleksandrovna , Svetitskaya Yana V. , Trifanov Vladimir , Kolesnikov Evgeniy N. 
Published: February 2020

90 Background: Complete or partial deficiency of the DPD enzyme due to genetic polymorphisms of the DPYD gene causes acute toxicity of fluoropyrimidines, which are widely used in combination chemotherapy regimens for various malignant neoplasms. The purpose of the study: to identify polymorphisms of the DPYD gene significant for 5-fluorouracil-induced toxicity. Methods: Venous blood samples from Caucasian patients were used to identify alleles of *2А rs3918290, 5* rs1801159, *13 rs55886062 and rs67376798 DPYD by RT-PCR and direct sequencing. Inclusion criteria were: verified diagnosis of gastrointestinal tumors, age>18 years old, fluoropyrimidine-containing regimes of treatment. Results: 104 pts were included, 54% were female. Mean age-61 years. Colorectal cancer was found in 80.7% pts, non-colorectal in 19.3% pts. Hematological and non-hematological toxicity Gd.3-4 was found in 24% pts. Allele * 5rs18011595, which causes enzyme deficiency was found in 28% of patients, (frequency was 0.281) which is significantly higher than the population frequency of the allele charactering for Caucasoid population (p <0.05). Meanwhile genotyping did not reveal the *2A, *13 alleles and rs67376798 alleles in the DPYD gene. Conclusions: *5rs1801159 allele was found as the main DPYD polymorphism associated with fluoropyrimidine toxicity in Caucasian pts with gastrointestinal tumors.
Neoadjuvant mFOLFOXIRI chemotherapy-improved survival benefit comparing with CRT in locally advanced rectal cancer: A propensity score matched analysis from two prospective trials.
Authors: Zhang Jianwei , Li Jianxia , Xie Xiaoyu , Cai Yue , Hu Huabin , Wu Zehua , Ling Jiayu , Deng Yanhong 
Published: February 2020

98 Background: Neoadjuvant chemoradiotherapy (CRT) is the standard of treatment for locally advanced rectal cancer, but it delays administration of systemic chemotherapy, leading to high incidence of distant metastases. To enhance systemic chemotherapy and avoid the damage of radiation, neoadjuvant chemotherapy with mFOLFOXIRI had been investigated. However, no randomized comparison assessing the efficacy of mFOLFOXIRI versus CRT in LARC. Methods: 145 LARC patients received CRT as neoadjuvant treatment in the phase III FOWARC study (NCT01211210) and 103 patients received mFOLFOXIRI alone preoperatively in a phase II study (NCT02217020). A propensity score-adjusted method was adopted to provide an estimation of the benefit from the enhancive chemotherapy regimen as neoadjuvant treatment in terms of survival and activity parameters. Results: In the original cohort, patients in the mFOLFOXIRI group were younger with the median age of 48 versus 56 years old in the CRT group. More patients with tumor length over 5 cm and cT3 or N2 disease in the mFOLFOXIRI group ( P< 0.05). After propensity score adjusted matching, 73 patients were comparable in each groups. The pCR rate was 23.3% in thd mFOLFOXIRI group versus 13.7% in the CRT group, respectively (P = 0.14). The proportion of ypStage 0-I was 45.2% versus 39.7%, respectively (P = 0.5). The local recurrence rate was comparable between the two groups (5.5% vs. 4.1%, P= 0.70). But mFOLFOXIRI decrease the incidence of distant metastasis (8.2% vs. 27.4%, P= 0.002). And the 3 year disease free survival was 86.8% in the mFOLFOXIRI group versus 75.8% in the CRT group, respectively ( P= 0.049). Lower incidence of anastomotic fistula was shown in mFOLFOXIRI alone group than that of CRT group (5.5% vs. 17.8%, P = 0.02). Grade 3/4 neutropenia was more commen in mFOLFOXIRI group (39.7% vs. 8.2%, P < 0.001). Conclusions: Comparing with CRT, preoperative mFOLFOXIRI decreased the incidence of distant metastasis and improved 3 year DFS, and led to less toxicity and fewer postoperative complications. The phase III randomized study comparing FOLFOXIRI with CRT is still ongoing. Clinical trial information: NCT01211210 and NCT02217020.
A randomized phase III study of mFOLFOX6/bevacizumab combination chemotherapy with or without atezolizumab or atezolizumab monotherapy in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) metastatic colorectal cancer (mCRC): Colorectal Cancer Metastatic dMMR Immuno-Therapy (COMMIT) study (NRG-GI004/SWOG-S1610).
Authors: Rocha Lima Caio Max Sao Pedro , Yothers Greg , Jacobs Samuel A. , Sanoff Hanna Kelly , Cohen Deirdre Jill , Guthrie Katherine A , Henry Norah Lynn , Ganz Patricia A. , Kopetz Scott , Lucas Peter C. , Blanke Charles David , Wolmark Norman , Hochster Howard S. , George Thomas J. , Overman Michael J. 
Published: February 2020

TPS260 Background: Deficient DNA mismatch repair (dMMR) colorectal cancer (CRC) is highly immunogenic. Preclinical data showed synergistic interactions among FOLFOX, anti-VEGF, and programmed cell death-1 (PD-1) pathway blockade. Prior phase I study of mFOLFOX6/ bevacizumab (bev) + atezolizumab (atezo) was well tolerated and enhanced intratumoral infiltration of CD8+ T cells. We hypothesize that the dMMR subset of CRC may be effectively targeted with combination of PD-1 pathway blockade and mFOLFOX6/bev. Methods: This is a prospective randomized phase III open-label trial. Pts (N=347) with mCRC dMMR will be randomized to three trial arms (1:1:1): mFOLFOX6/bev; atezo monotherapy; or mFOLFOX6/bev + atezo. Stratification factors include BRAFV600E status, metastatic site, and prior adjuvant CRC therapy. Primary endpoint is progression-free survival (PFS) assessed by study investigator of mFOLFOX6/bev/atezo and atezo monotherapy compared to mFOLFOX6/bev. Secondary endpoints include OS, objective response rate, safety profile, disease control rate, duration of response, and PFS by retrospective central review. Health-related quality of life is an exploratory objective. Archived tumor tissue and blood samples will be collected for correlative studies. Key inclusion criteria are: mCRC without prior chemotherapy for advanced disease; dMMR tumor determined by local CLIA-certified IHC assay (MLH1/MSH2/MSH6/PMS2); availability of archived tumor tissue for central confirmation of dMMR status; and measurable disease per RECIST. Activated 11-7-17. As of 9-11-19, enrollment continues with 44/347 pts enrolled. Clinical trial: NCT02997228. Support:U10CA180868, -180822, -180888, -180819, UG1CA189867, U24CA196067; Genentech, Inc. Clinical trial information: NCT02997228.
NSABP FC-10: Phase IB study of pembrolizumab in combination with premetrexed + oaliplatin in patients (pts) with chemo-refractory metastatic colorectal cancer (mCRC).
Authors: Lee James J. , Yothers Greg , George Thomas J. , Krauss John C. , Maalouf Bassam Nabih , Parekh Hiral D. , Krishnamurthy Anuradha , Vehec Kelly R. , Wolmark Norman , Allegra Carmen Joseph , Jacobs Samuel A. 
Published: February 2020

TPS262 Background: The majority of mCRC pts are microsatellite stable (MSS), have poor intratumoral CD8+ T cell infiltration, and no clinical response to immunotherapy checkpoint inhibitors. Preclinical studies suggest that chemotherapy may synergize with anti-PD-1. In non-small cell lung cancer (NSCLC), the combination of pembrolizumab (PemB), pemetrexed (PemT), + carboplatin demonstrated synergistic activity. This study will combine PemB with PemT, then that combination + oxaliplatin (Ox). The rationale for addition of Ox to PemT is that enhanced immunogenic cell death may induce CD8+ T cell infiltration into CRC tumors and model the mechanism of cytotoxicity seen in NSCLC. Thus, the combination of PemB+ PemT + Ox may induce synergistic antitumor immune activity. Methods: This multi-center phase Ib trial is actively enrolling pts with incurable mCRC with prior treatment for mCRC including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, and if RAS wild-type, anti-EGFR therapy. Measurable disease by imaging (RECIST 1.1) is required. Standard ineligibility includes active infections, systemic steroid use, or other conditions contraindicating immunotherapy. Cohort 1 will receive PemB + PemT; Cohort 2 will receive PemB + PemT + dose-escalated Ox. Imaging will be performed every 6 wks. The primary aim of Cohort 1: to evaluate for safety and efficacy using doses of PemB and PemT that have been studied in NSCLC. The primary aim of Cohort 2: to evaluate the safety, tolerability, and efficacy of PemB in combination with PemT + Ox. The RP2D of the 3-drug combination will be at the MTD taking into account toxicity profiles of study therapy agents. Secondary aims: to evaluate the clinical benefit rate of the doublet and triplet combinations in pts with chemo-refractory MSS mCRC and to estimate progression-free survival and overall survival in pts with MSS mCRC treated with these combinations. The cohorts will be analyzed separately with descriptive intent only. Maximum enrollment is 33 pts. Support: Merck; Lilly; NSABP Foundation, Inc. Clinical trial information: NCT03626922.
MONARCC: A randomized phase II study of panitumumab monotherapy and panitumumab (pan) plus 5 Fluorouracil (FU) as first-line therapy for RAS and BRAF wild type metastatic colorectal cancer (mCRC): An AGITG clinical trial.
Authors: Tebbutt Niall C. , Steer Christopher B. , Sjoquist Katrin Marie , Chantrill Lorraine A. , Karapetis Christos Stelios , Nott Louise M. , Espinoza David , Oostendorp Martinus , Yip Sonia , Cuff Jeff , Burge Matthew E. 
Published: February 2020

TPS271 Background: Pan added to combination chemotherapy is established first-line therapy for RAS and BRAF wild type mCRC. Elderly patients are not well represented in clinical trials and may be more suited to treatment protocols with lower toxicity risks; FU plus bevacizumab (bev) is commonly used. Treatment related efficacy, toxicity, impact on quality of life and other outcomes of pan based regimens in an elderly population have not been well studied. Methods: A prospective non-comparative randomized phase 2 study. Australian Clinical Trials Registry Number: ACTRN 12618000233224. Main inclusion criteria include: Untreated patients aged 70 years or older; RAS and BRAF wild type; ECOG performance 0-2. Randomisation 1:1, stratified by primary tumour side, performance status, number of metastatic sites; to pan 6mg/kg 2 weekly or panitumumab plus FU 400 mg/m² bolus; leucovorin 200mg/m²; FU 2400mg/m² 48 hour infusion 2 weekly. Primary endpoint is 6-month progression-free survival (PFS). Sample size is 80 patients based on expected 6-month PFS rate of 73% with FU and bev. Using the method of Metha-Cain, if 24 or more patients are progression free at 6 months, the one sided 95% confidence interval includes 73% and we declare similar activity. Secondary endpoints include overall survival; toxicity and overall treatment utility, a composite measure of treatment benefit based on radiology, clinical progress, toxicity and patient reflection of the impact of treatment on their daily lives. Patients undergo a comprehensive health assessment at baseline and limited health assessment at 4 months. Physical activity trackers are worn for 2 weeks at treatment commencement and again at week 16. Tumour tissue and blood samples (at baseline, cycle 3 day 1 and at 24 weeks) will be collected for translational research. First site opened in June 2018. Twelve patients have been recruited to date from 9 sites in Australasia. Eighteen sites were open as at September 2019. Clinical trial information: 12618000233224.
Circulating tumor DNA-based decision for adjuvant treatment in colon cancer stage II evaluation: (CIRCULATE-trial) AIO-KRK-0217.
Authors: Folprecht Gunnar , Reinacher-Schick Anke , Tannapfel Andrea , Weitz Juergen , Kossler Thibaud , Weiss Lukas , Aust Daniela Ellen , von Bubnoff Nikolas , Kramer Michael , Thiede Christian 
Published: February 2020

TPS273 Background: The benefit of adjuvant chemotherapy in stage II colon cancer is unclear, and clear clinical or molecular marker are not available for decision making. Recently, postoperative circulating tumour (ct)DNA has been demonstrated to be prognostic in colorectal cancer and other tumours. Methods: For the CIRCULATE trial we enrol patients (pts) with colon cancer stage II in Germany (AIO), Austria (ABCSG) and Switzerland (SAKK). Microsatellite stable pts are screened after resection of the primary by analysing the tumour block with panel sequencing and measuring patient specific mutations in the postoperative plasma sample. MSI-H pts are excluded from the trial. ctDNA positive (ctDNApos) pts are randomised (2:1) to receive adjuvant capecitabine based chemotherapy or no chemotherapy. Oxaliplatin can be added according to investigator’s choice. ctDNA negative (ctDNAneg) pts are randomised (1:4) to be followed-up within the study or to receive standard follow-up outside the trial. Pts in the follow-up group and their investigators are blinded for the ctDNA result. The primary aim is to compare the disease free survival (DFS) in ctDNApos pts randomised to chemotherapy or to follow-up. Secondary aims are to compare the overall survival (OS) in ctDNApos pts with or without chemo, to compare the DFS and OS in ctDNApos vs. ctDNAneg follow-up pts, to describe the DFS and OS in ctDNAneg pts, to describe the location of recurrences/metastases according ctDNA status, the ctDNA clearance rate and time to ctDNA negativity during adjuvant chemotherapy, further translational endpoints, and safety. To demonstrate a treatment effect in the ctDNA group with a hazard ratio of 0.617 (3 year DFS rate of 42.5 % vs. 25 %), 231 ctDNApos will be randomised (approx. 2310 pts in total) from 2019 – 2022. Clinical trial information: NCT04089631.
Tislelizumab plus chemotherapy as first-line treatment for unresectable, locally advanced recurrent/metastatic esophageal squamous cell carcinoma.
Authors: Yoon Harry H. , Kato Ken , Hubner Richard , Raymond Eric , Tao Aiyang , Liu Sumei , Qazi Ibrahim , Xu Jian-Ming 
Published: February 2020

TPS462 Background: Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer, particularly in Asian countries. Inhibition of the PD-1/PD-L1 axis has demonstrated antitumor activity in patients with advanced unresectable or metastatic ESCC. Tislelizumab, an investigational humanized IgG4 monoclonal antibody with high affinity and binding specificity for PD-1, was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Results from early phase clinical studies suggest tislelizumab, as a single agent or in combination with chemotherapy, was generally well tolerated and had antitumor activity in patients with solid tumors, including ESCC. Methods: This global, phase 3, randomized, placebo-controlled, double-blind study (NCT03783442) is designed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment of unresectable, locally advanced recurrent or metastatic ESCC. Adult patients with histologically confirmed unresectable ESCC, or locally advanced recurrent/metastatic disease with a ≥6 month treatment-free interval, are eligible; palliative radiation administered > 4 weeks from study initiation is allowed. Patients who received prior anti-PD-(L)1, anti-PD-L2, or first-line therapy are ineligible. Patients (n≈480) will be randomized 1:1 to receive tislelizumab 200 mg IV every 3 weeks (Q3W) plus investigator-chosen chemotherapy (ICC) or placebo plus ICC. ICC options include: platinum (plat; cisplatin 60-80 mg/m2 or oxaliplatin 130 mg/m2 IV Q3W) + 5-FU 750-800 mg/m2 by continuous IV infusion over 24 hours for 5d Q3W; or plat + capecitabine 1000 mg/m2 orally BID for 14d Q3W; or plat + paclitaxel 175 mg/m2 IV Q3W. Progression-free and overall survival are primary endpoints; secondary endpoints include objective response rate, duration of response, and health-related quality of life. Safety will be assessed by monitoring adverse events, physical examinations, vital signs, and electrocardiograms. This study is actively enrolling. Clinical trial information: NCT03783442.
A phase II study of futibatinib (TAS-120) in patients (pts) with advanced (adv) solid tumors harboring fibroblast growth factor receptor (FGFR) genomic aberrations.
Authors: Hollebecque Antoine , Doi Toshihiko , Saavedra Omar , Takahashi Osamu , He Helen , Benhadji Karim A. , Shitara Kohei 
Published: February 2020

TPS470 Background: FGFR genomic aberrations are known to drive oncogenesis in multiple tumor types via FGFR signaling pathway dysregulation. Futibatinib is an oral, highly selective, irreversible FGFR1–4 inhibitor that has shown potent antiproliferative activity against FGFR-deregulated tumors of diverse tissue origins in preclinical studies. In a phase 1 dose-escalation/expansion study, futibatinib showed promising antitumor activity and tolerability in previously treated pts with tumors harboring FGFR aberrations. This phase 2 study was designed to evaluate the efficacy and safety of futibatinib in pts with tumors harboring FGFR aberrations. The study will enroll pts in multiple cohorts based on diagnosis and FGFR aberration status; cohorts enrolling pts with adv solid tumors are reported here. Methods: In this global, open-label, phase 2 study, pts (≥18 years; Eastern Cooperative Oncology Group performance status of 0 or 1) will be enrolled in cohort A (~60 pts with metastatic/locally adv solid tumors, except primary brain tumors or intrahepatic cholangiocarcinoma, harboring FGFR1–4 rearrangements and with disease progression after standard treatment) or cohort B (~35 pts with metastatic/locally adv gastric tumors harboring FGFR2 amplifications and with ≥2 prior therapies). Key exclusion criteria are clinically significant alterations in calcium–phosphorus homeostasis, ectopic mineralization/calcification, and prior FGFR inhibitor treatment. Pts will receive 20 mg futibatinib once daily in a continuous 28-day cycle until disease progression, unacceptable toxicity, or other discontinuation criteria are met. The primary endpoint is objective response rate (ORR) per independent central review. Secondary endpoints include ORR per investigator, disease control rate, duration of response, progression-free survival, overall survival, and safety. The anticipated start date is in April 2020.