bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of new treatment strategies for mCRC: Effect of online education on clinician knowledge and confidence.
Authors: Fisher Geoff Roy , Koekkoek Sanneke , Vandenbroucque Juliette , Taieb Julien 
Published: January 2021

67 Background: This study determined whether online continuing medical education could improve the knowledge and confidence of cliniciansin the application of the latest strategies for the treatment of mCRC. Methods: A 30-minute online video panel discussion was launched for physicians outside the USA in March 2020. Data was collected to May 2020. Educational effect assessed with repeated-pairs pre-/post-activity, where individual participants served as their own control. 3 multiple-choice, knowledge questions and 1 self-efficacy, 5-point Likert scale confidence question were analyzed. Chi-squared test assessed pre- to post-activity change (5% significance level, P < .05). Magnitude of change in total number of correct responses overall, and for each question, were determined with Cramer’s V ( < .06 = Modest, 0.06-0.15 = Noticeable, .16-.26 = Considerable, > .26 = Extensive). Results: 108 oncologists (oncs) and 33 gastroenterologists (gastros) completed pre- and post-activity questions. A positive educational effect was observed for oncs (noticeable effect, V = .123, P < .01); average % correct increased from 71 to 81%. For gastros, there was a noticeable effect (V = .06) but P was not significant; correct responses increased from 49 to 56%. Clinicians with 3/3 answers correct increased post-activity (37 to 54% for oncs, 18 to 24%, for gastros). For oncs, improvements in % of correct responses post-activity were seen for questions on tailoring treatment to primary tumour location, outcome of the CRICKET trial on cetuximab re-challenge, and outcome of the BEACON trial in BRAF mutated mCRC (11%, 21%, and 13% relative changes, respectively). Relative changes of 25%, 18% and -17%, respectively, were observed for gastros. % of clinicians mostly or very confident with selecting optimal treatment strategy across the continuum of care improved post-activity, increasing from 33 to 58% for oncs and from 27 to 36% for gastros. Conclusions: This on-demand, online video panel discussion resulted in a positive education effect. However, the sample size for gastros was small and the post-activity change was not significant. Knowledge gaps remained post-activity, indicating the need for further education to support optimisation of the treatment of mCRC.
Initial experience of patients treated in a real-world clinical setting with bevacizumab-awwb: The first FDA-approved biosimilar to bevacizumab.
Authors: Jin Ran , Accortt Neil A , Sandschafer Darcie , Lawrence Tatiana , Loaiza-Bonilla Arturo 
Published: January 2021

81 Background: Bevacizumab-awwb is the first anti-cancer biosimilar and the first biosimilar to bevacizumab approved by the FDA. It was launched in the United States on July 19, 2019. Bevacizumab-awwb approval was based on a phase 3 study in a pre-determined sensitive population of non-squamous non-small cell lung cancer (NSCLC) patients. This study investigated initial use of bevacizumab-awwb, across its approved indications for advanced cancer management, in real-world US community and academic oncology practices. Methods: This retrospective observational study described demographic and clinical characteristics of patients who received bevacizumab-awwb using structured patient-level data from the nationwide de-identified Oncology Services Comprehensive Electronic Records (OSCER), a Flatiron Health EHR-derived database. The database is longitudinal, demographically and geographically diverse, and includes more than 2.2 million US cancer patients from >280 cancer clinics. This analysis included adult patients who received ≥1 bevacizumab-awwb infusion between July 30, 2019 and April 30, 2020 and focused on describing initial biosimilar uptake in cancer patient populations beyond NSCLC. Results: First use of bevacizumab-awwb was in mCRC and occurred within 10 days of product launch. All bevacizumab-awwb approved cancer indications were represented among 2,422 patients treated with bevacizumab-awwb. Initial use of bevacizumab-awwb across indications: mCRC (68%), NSCLC (14%), brain cancer (11%), cervical cancer (5%), metastatic renal cell carcinoma (1%). Among 1657 mCRC patients treated with bevacizumab-awwb, 55% were male with a median age of 65 years (y). Most patients were white (60%), with ECOG scores of 0/1 (84%), and median body weight was 78 kg. Among mCRC patients, 59% had received the reference product before receiving the biosimilar. Among patients with other tumor types, 42-50% had prior bevacizumab exposure. Among mCRC patients with prior exposure to bevacizumab, 67% received bevacizumab-awwb within 28 days of last infusion of reference product (Table). Demographic and clinical characteristics were comparable between patients with and without prior bevacizumab use. Conclusions: Early evidence suggests physicians are comfortable initiating or transitioning patients to the first FDA-approved biosimilar to bevacizumab, with little evidence that demographic characteristics differ between patients with and without previous treatment with bevacizumab. Future analyses will determine whether these patterns persist across all indications. [Table: see text]
Development of a cure model for the estimation of long-term outcomes in patients with microsatellite instability(MSI)-high metastatic colorectal cancer (mCRC) receiving immune-checkpoint inhibitors (ICIs).
Authors: Pietrantonio Filippo , Infante Gabriele , Lonardi Sara , Corti Francesca , Intini Rossana , Salati Massimiliano , Fenocchio Elisabetta , Belli Carmen , Cremolini Chiara , Fucà Giovanni , Prete Alessandra Anna , Quarà Virginia , Manca Paolo , Spallanzani Andrea , Morano Federica , Di Bartolomeo Maria , Curigliano Giuseppe , De Braud Filippo G. , Zagonel Vittorina , Miceli Rosalba 
Published: January 2021

87 Background: Anti-PD-(L)1-based therapy yielded unprecedented efficacy in patients with MSI-high mCRC. A relevant proportion of subjects may achieve long-term disease control when receiving ICIs, particularly anti-PD-1 plus anti-CTLA-4 combo. However, some patients still experience treatment refractoriness or short-term clinical benefit. Methods: We analyzed data of 163 patients with MSI-high mCRC treated with anti-PD-1 +/- anti-CTLA-4 agents. The endpoint was progression-free survival (PFS); multivariable analyses were performed using a cure model (Othus et al, CCR 2012), which allows to test which factors, including ICI type, could identify patients achieving long-term disease control. To account for biases consistent with non-random ICI assignment, we estimated a propensity score (covariates: ECOG PS, age, sex, primary tumor location, its resection, adjuvant treatment, synchronous presentation of mets, mucinous histotype, RAS/BRAF status, n. prior treatment lines, previous chemo, n. metastatic sites, presence of peritoneal, lung, liver, bone, brain, nodal mets), and then in the cure model we applied an inverse-probability-of-treatment-weight (IPTW) based on propensity score. A beforehand variable selection was operated using a random survival forest (RSF) model (RSF covariates: all the propensity score covariates plus ICI line and ICI type, platelets count (PLT), NLR, LDH), where we introduced a weight system in order to adjust variable selection net of ICI type. Results: RFS selected 5 variables: ICI type, ECOG PS, NLR, PLT and N. prior lines, the combination of which allowed to estimate the cure probability: the higher the probability the greater the chance of achieving long-term disease control. The Table shows the odds ratio estimates, defining the chance of being “cured” according to the values of the selected variables. ICI type was significantly associated with long-term disease control: patients treated with anti CTLA-4-combo achieved the highest chance of being cured, 3.41 times greater than the chance of patients treated with anti PD-1 mono. The median cure probability was as higher as 70.1% (IQR: 51.9-81.0%) with CTLA-4-combo vs 34.8% (IQR: 18.4-51.9%) with anti-PD-1 mono; the probability within treatment groups was varying according to ECOG PS, NLR, PLT and n. prior lines. Conclusions: Based on 5 variables including the ICI treatment type, a nomogram was built in order to estimate the cure probability in patients with MSI-high mCRC and potentially assist clinicians in their clinical practice. [Table: see text]
Implementation of hepatic artery infusion (HAI) chemotherapy for unresectable colorectal liver metastases (CRLM): The University of Miami experience.
Authors: Pimentel Agustin , Kronenfeld Joshua , Dudeja Vikas , Merchant Nipun B. , Gallegos Lauren Nicole , Kelly Kristin , McGhee Vivian , Naveda Alissette , Ng-Chen Hoyan , Lockhart A. Craig , Hosein Peter Joel , Ezenwajiaku Nkiruka , Ardalan Bach , Datta Jashodeep 
Published: January 2021

96 Background: In patients with unresectable liver-confined CRLM, regional chemotherapy via HAI in combination with modern systemic chemotherapy (CT) can achieve hepatic disease control and expand surgical resectability. We describe patient selection and early outcomes following implementation of a HAI program at our tertiary referral academic center. Methods: We analyzed demographics, previous systemic treatment, primary tumor location, molecular profiling, extent of hepatic/extrahepatic disease, perioperative HAI outcomes (toxicity, conversion to resection/ablation, radiographic response), and overall survival (OS) in CRLM patients selected for HAI treatment (01/2018—06/2020) after multidisciplinary review. Results: Of 35 patients with unresectable CRLM (primary: colon, n = 24; rectum, n = 11) selected for HAI, 57% were heavily pre-treated (with at least 2 lines of pre-HAI systemic chemotherapy), 71% had a Fong clinical risk score ≥3, 86% presented with synchronous disease, 80% had bilobar metastasis, and 86% had > 5 tumors. All tumors were microsatellite stable, with 20% harboring KRAS/NRAS mutations and none had class I/II BRAF mutations. HAI was initiated at a median 14 (IQR 3, 64) months after CRLM diagnosis, and administered for a median of 7 (range 2, 16) cycles; 91% of patients (31/34) received concurrent HAI and systemic chemotherapy. Although most (69%) patients experienced some degree of hepatic toxicity during HAI therapy resulting in FUDR dose reduction and steroid administration, biliary sclerosis requiring intervention was observed in only 3 (9%) of patients. The overall perioperative morbidity was 17%, and there were no surgical-related 90-day mortalities following HAI pump placement. Excluding patients who initiated HAI treatment within the last 3 months of the study period (n = 3), 13 of 32 patients (41%) were rendered disease-free in the liver following complete resection and/or ablation in combination with HAI/systemic chemotherapy; in the remaining 19 patients (59%), hepatic progression-free survival was 7.3 months (IQR 4, 12). At a median follow-up of 11.2 months, post-HAI median OS for the overall cohort was 12.3 (IQR 7, 20) months. Patients undergoing complete resection/ablation demonstrated improved survival compared with those with progressive disease (median 20 vs 12 months, respectively). Conclusions: Implementation of a HAI program for multimodality liver-directed management of unresectable CRLM is feasible and is associated with meaningful clinical outcomes unlikely to be achieved with systemic therapy alone in heavily pre-treated patients.
Phase II study of pembrolizumab after chemoradiotherapy (CRT) as adjuvant therapy for locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients at high risk of recurrence following preoperative CRT plus surgery.
Authors: Hsu Chih-Hung , Guo Jhe-Cyuan , Huang Ta-Chen , Kuo Hung-Yang , Lin Chia-Chi , Hsu Feng-Ming , Cheng Jason C. , Huang Pei-Ming , Lee Jang-Ming 
Published: January 2021

TPS259 Background: LA-ESCC is a potentially curable disease, for which preoperative CRT followed by esophagectomy is a standard-of-care. Previous studies have identified that close/involved margin and lymph node metastasis with extranodal invasion (ENI) in post-CRT surgical specimens are associated with increased risk of recurrence. In CheckMate-577 trial, adjuvant nivolumab significantly improved disease-free survival (DFS) in patients with esophageal cancer treated with preoperative CRT and surgery; in another trial (the “PACIFIC” trial), adjuvant durvalumab has significantly improved overall survival (OS) in stage III non-small cell lung cancer treated with definitive CRT. We hypothesize that adding pembrolizumab to CRT as an adjuvant therapy would improve the outcomes of LA-ESCC patients who are treated with preoperative CRT plus esophagectomy and with high-risk of recurrence. Methods: This single institution single-arm phase II study include patients with histologically confirmed LA-ESCC (AJCC 7th staging system:cT3-4aN0M0 or T1-4aN1-3M0) harboring at least one risk factor (closed/involved margin, ENI, or ypN2-3) in post-CRT surgical specimens. Patients with adenocarcinoma of esophagus or gastroesophageal junction or synchronously diagnosed with a squamous cell carcinoma of aero-digestive way other than ESCC are excluded. Patients enrolled will receive adjuvant weekly cisplatin–CRT (cisplatin, 30mg/m2 for 2 cycles every week; radiotherapy, 180-200 cGy/fraction for 10-13 times) followed by pembrolizumab (200 mg, every 3 weeks, for 18 cycles). The primary endpoint of this study is 1-year relapse-free survival (RFS) rate; and the key secondary endpoints include RFS, 3-year RFS rate, OS, 3-yr OS rate, toxicity and safety. The study, registered with clinical trial ID of NCT03322267, started patient enrollment in Aug 2018. As of Aug of 2020, 11 of 46 planned patients have been enrolled. Clinical trial information: NCT03322267.
A phase Ib/II, multicenter, open-label, dose-escalation, and dose-expansion study evaluating trastuzumab deruxtecan (T-DXd, DS-8201) monotherapy and combinations in patients with HER2-overexpressing gastric cancer (DESTINY-Gastric03).
Authors: Janjigian Yelena Y. , Viglianti Natasha , Liu Feng , Mendoza-Naranjo Ariadna , Croydon Liz 
Published: January 2021

TPS261 Background: For patients (pts) with HER2-overexpressing metastatic gastric cancer, trastuzumab + chemotherapy is a standard first-line option but provides only a modest overall survival (OS) benefit vs chemotherapy. T-DXd is an antibody-drug conjugate consisting of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and a membrane-permeable topoisomerase I inhibitor payload. Results from a phase 1 trial showed promising antitumor activity (confirmed objective response rate [ORR], 43.2%) in pts with heavily pretreated HER2+ metastatic gastric cancer who received T-DXd (5.4 or 6.4 mg/kg; Shitara K, et al. Lancet Oncol. 2019;20:827-836). Here we describe the phase 1b/2 DESTINY-Gastric03 trial (NCT04379596) evaluating T-DXd monotherapy and combinations in pts with HER2-overexpressing gastric cancer. Methods: This is an open-label, multicenter, 2-part, phase 1b/2 study in pts with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization positive) locally advanced, unresectable or metastatic gastric or gastroesophageal junction cancer. In part 1 (dose escalation), pts who had received prior trastuzumab-containing therapy will be assigned to 1 of 5 arms: (1) T-DXd + 5-fluorouracil (5-FU); (2) T-DXd + capecitabine (C); (3) T-DXd + durvalumab; (4) T-DXd + 5-FU or C + oxaliplatin (Ox); or (5) T-DXd + 5-FU or C + durvalumab. In part 2 (dose expansion), pts with no prior treatment for metastatic disease will be randomized across 4 arms: (1) T-DXd; (2) trastuzumab + 5-FU or C + Ox or cisplatin; (3) T-DXd + 5-FU or C ± Ox; or (4) T-DXd + 5-FU or C + durvalumab. In part 2, pts will be stratified by HER2 status. Primary endpoints are safety, determination of recommended phase 2 doses (part 1), and investigator-assessed confirmed ORR per RECIST v1.1 (part 2). Secondary endpoints include confirmed ORR (part 1), disease control rate, duration of response, progression-free survival (all per investigator), OS, safety (part 2), pharmacokinetics, and immunogenicity. Clinical trial information: NCT04379596.
Margetuximab (M) combined with anti-PD-1 (retifanlimab) or anti-PD-1/LAG-3 (tebotelimab) +/- chemotherapy (CTX) in first-line therapy of advanced/metastatic HER2+ gastroesophageal junction (GEJ) or gastric cancer (GC).
Authors: Catenacci Daniel V.T. , Rosales Minori Koshiji , Chung Hyun Cheol , Yoon Harry H. , Shen Lin , Moehler Markus H. , Kang Yoon-Koo 
Published: January 2021

TPS264 Background: Trastuzumab (T), a monoclonal antibody (mAb) targeting HER2, is standard of care 1st-line therapy for advanced HER2+ GEJ/GC patients. M, an investigational Fc-engineered anti-HER2 mAb, targets the same HER2 epitope but with higher affinity for both 158V (high binding) and 158F (low binding) alleles of activating Fc receptor CD16A. Data suggest margetuximab coordinately enhances both innate and adaptive immunity, including antigen-specific T-cell responses to HER2. PD-1 and LAG-3 are T-cell checkpoint molecules that suppress T-cell function. Retifanlimab (also known as MGA012 or INCMGA00012) is a humanized, hinge-stabilized, IgG4 Κ anti-PD-1 mAb blocking binding of PD-L1 or PD-L2 to PD-1. Tebotelimab (also known as MGD013) is a humanized Fc-bearing bispecific tetravalent DART® protein that binds to both PD-1 and LAG-3, inhibiting their respective ligand binding. We previously reported that a CTX-free regimen of M+PD-1 blockade was well tolerated in GEJ/GC patients, and induced a 44% objective response rate (ORR) in a double-positive biomarker population. This was 2- to 3-fold greater than in historical controls with checkpoint inhibitors alone. This registration-directed trial assesses efficacy, safety, and tolerability of M+checkpoint inhibition ± CTX in metastatic/locally advanced, treatment-naïve, HER2+ GEJ/GC patients. Methods: This is a 2-cohort, adaptive open-label phase 2/3 study (NCT04082364). The first single arm, CTX-free cohort A, evaluates M+retifanlimab in HER2+ (immunohistochemistry [IHC] 3+) and PD-L1+ (excluding microsatellite instability high) patients. After 40 patients are evaluated for response/safety, additional patients will be enrolled if the threshold for continuation is met. In randomized cohort B, HER2+ (IHC 3+ or 2+/fluorescent in situ hybridization+) patients are enrolled irrespective of PD-L1 status. Part 1 of cohort B randomizes patients to 1 of 4 arms (50 patients each): control arm (T+CTX) or 1 of 3 experimental arms (M+CTX; M+CTX+retifanlimab; M+CTX+tebotelimab). CTX is investigator’s choice XELOX or mFOLFOX-6. Part 2 of cohort B consists of control (T+CTX) vs 1 experimental arm (M+CTX) + either retifanlimab or tebotelimab, depending on results from part 1; with 250 patients each. The primary efficacy endpoint for cohort A (both parts) is ORR per RECIST 1.1; for cohort B part 2 it is overall survival. Clinical trial information: NCT04082364.
Trial in progress: A feasibility study of multi-platform profiling using biospecimens from patients with resected biliary tract cancer.
Authors: Diehl Adam , Harris William Proctor , King Gentry Teng 
Published: January 2021

TPS359 Background: Biliary tract cancers (BTC) are rare malignancies with a high recurrence rate after resection of localized disease. FDA-approved systemic therapies for advanced disease are limited to combination chemotherapy and FGFR inhibitors for FGFR2-altered BTC. The tools of personalized medicine may guide management and expand treatment options for this disease. In multiple tumor types, circulating tumor DNA (ctDNA) has shown significant predictive power for recurrence after resection, but its utility has not yet been established in BTC. Organoid drug sensitivity screening may also inform and expand treatment options, particularly for patients without targetable mutations on next generation sequencing (NGS). Prospective concordance between organoid drug sensitivity and in vivo clinical responses to a given drug is needed to establish the value of this testing in BTC. We designed a clinical trial to determine the feasibility and physician-assessed utility of multi-platform profiling of resected BTC. Methods: This is an observational, non-randomized feasibility study to assess the ability to obtain NGS, ctDNA monitoring, and organoid drug sensitivity screening on patients with resected localized BTC. Secondary endpoints include physician-adjudicated utility of the profiling results for patient management, prospective concordance of organoid drug sensitivity with in vivo drug activity, and value of ctDNA in prediction of recurrence or response to therapy. Key eligibility criteria include a biopsy or clinical presentation consistent with BTC (excluding mixed HCC-cholangiocarcinoma), surgical candidacy for resection of measurable disease, and no prior targeted or investigational therapies. ctDNA is collected pre- and post-operatively, during adjuvant chemotherapy, during surveillance for up to 5 years and during systemic therapy for recurrent disease. Physician surveys are conducted before and after receipt of profiling results and then at time points where a change in management would be considered. Enrollment began in July 2020 with 5 of a planned 20 patients enrolled at the time of submission. Clinical trial information: NCT04561453.