Editorial Support Research Articles

Preface

2024 4th International Conference on Fluid and Chemical Engineering (ICFCE 2024) has been successfully held on July 26-27, 2024, in Wuhan China as a virtual event. Organized by Hubei Zhongke Institute of Geology and Environment Technology, ICFCE 2024 intends to invite worldwide famous scientists, experts, scholars, and researchers for academic presentations. ICFCE 2024 proceeding is a collection of outstanding submissions in the field of biofluid mechanics, chemically reacting fluids and combustion, computational fluid dynamics (CFD), experimental fluid mechanics, flow through porous media, fluid–solid interactions (FSI), geophysical fluid dynamics, granular/suspension flows, heat and mass transfer, hydrodynamics, physical, theoretical and computational chemistry, chemical engineering fundamentals, chemical reaction engineering, chemical engineering equipment design and process design, thermodynamics, catalysis & reaction engineering, particulate systems, crystallization, etc. Around 65 articles were selected from 146 submissions after peer-review, and authors and guests participated in ICFCE 2024 with keynote speeches, oral presentations and posters, promoting the communication among researchers and experts from institutes and universities, including University of Sharjah, The University of Manchester, Harbin Engineering University, China University of Petroleum (East China), Shanghai Maritime University, Jiangxi University of Science and Technology, Nagoya University, Marine Design & Research Institute of China, Tianjin Transportation Technical College, Okayama University, etc. Cordial gratitude is delivered to Technical Program Committee of ICFCE 2024 for the professional work on guarantying the high standard of conference as well as the proceedings. We believe the proceedings will enhance the exchange of ideas and state-of-art knowledge on Fluid and Chemical Engineering. Finally, we thank all the staff members at IOP Publishing for their valuable editorial support. Professor Omid Mahian Xian Jiaotong University, China Associate Professor Sébastien Déon University of Bourgogne-Franche-Comté, France List of Technical Committee is available in the pdf

Understanding author choices in the current conservation publishing landscape.

Conservation literature addresses a broad spectrum of interdisciplinary questions and benefits. Conservation science benefits most when a diverse range of authors are represented, particularly those from countries where much conservation work is focused. In other disciplines, it is well known that barriers and biases exist in the academic publishing sphere, which can affect research dissemination and an author's career development. We used a discrete choice experiment to determine how 7 journal attributes affect authors' choices of where to publish in conservation. We targeted authors directly by contacting authors published in 18 target journals and indirectly via communication channels for conservation organizations. We only included respondents who had previously published in a conservation-related journal. We used a multinomial logit model and a latent class model to investigate preferences for all respondents and distinct subpopulations. We identified 3 demographic groups across 1038 respondents (older authors from predominantly middle-income countries, younger authors from predominantly middle-income countries, and younger authors from high-income countries) who had published in conservation journals. Each group exhibited different publishing preferences. Only 2 attributes showed a consistent response across groups: cost to publish negatively affected journal choice, including authors in high-income countries, and authors had a consistent preference for double-blind review. Authors from middle-income countries were willing to pay more for society-owned journals, unlike authors from high-income countries. Journals with a broad geographical scope that were open access and that had relatively high impact factors were preferred by 2 of the 3 demographic groups. However, journal scope and open access were more important in dictating journal choice than impact factor. Overall, different demographics had different preferences for journals and were limited in their selection based on attributes such as open access policy. However, the scarcity of respondents from low-income countries (2% of respondents) highlights the pervasive barriers to representation in conservation research. We recommend journals offer double-blind review, reduce or remove open access fees, investigate options for free editorial support, and better acknowledge the value of local-scale single-species studies. Academic societies in particular must reflect on how their journals support conservation and conservation professionals.

Co‐creative gift systems within digital platforms

AbstractThis study explores co‐creative gift systems within digital platforms. We define co‐creative gift systems as systems where consumers actively engage in content creation and co‐creation, disseminating original artistic digital gifts (i.e., content such as novels, videos, music) on digital platforms and engaging in collaborative exchanges that shape the work in progress. Using a qualitative methodology, including netnography and guided introspections, we analyze 3 years of netnographic data on Wattpad, a platform for developing and publishing written fiction. Our findings reveal the building of varying relational ties within the gift system, from casual interactions to deep connections that foster communities of practice and fandoms, and fluid role transitions between givers and recipients. These interactions and transitions impact the development of the digital gift through editorial support, narrative co‐creation, and independent reviews. This study contributes to the literature on gift giving by emphasizing the role of co‐creative gift systems in enhancing digital community interactions and content co‐creation. Future research directions are suggested to further explore co‐creative gift systems across various digital platforms and their implications for consumer research and digital content production.

The Appropriation of Fixed Capital: A Metaphor?

In the debate on the impact of digital technology on society, considering that digital technologies have profoundly changed the way we learn and communicate, and especially the “mode of production”, and remembering that this transformation takes place in an era of capitalist economic hegemony – the hypothesis often arises that the producer is transformed by the use of this machine. There is speculation that the user incorporates the instrumentality of the digital machine. Furthermore, when one recognizes that capitalist production develops its process of value creation by using cognitive labour power (and that this form of value production becomes more and more prominent) the technological incorporation of the cognitive cooperation of workers, seems to become ever more central to capitalist exploitation. Consequently, in the Marxist debate, people have started talking of an “appropriation of fixed capital” by the digitized worker and by the cognitive producer. This article asks: Are these simply metaphors? It discusses the relationship of living labour and digital machines. It stresses that digital machines do not determine society and human fate but can be appropriated by social struggles for the commons. It grounds the analysis of the digital in Karl Marx’s works on technology and fixed capital. It concludes that autonomous spheres of digital self-valorisation can be established through social struggles that aim at advancing social co-operation and the commons. Acknowledgement: This article was translated from Italian to English by Michele Ledda with editorial support by Christian Fuchs, David Chandler, and Sara Raimondi. The paper is based on a talk that Antonio Negri gave at the 7th ICTs and Society Conference “Digital Objects, Digital Subjects: An Interdisciplinary Symposium on Activism, Research & Critique in the Age of Big Data Capitalism” on May 20, 2017, at the University of Westminster in London. The video of this talk is available here: https://www.youtube.com/watch?v=htm5xwAl-kE The video of the commenting and Q&A session that followed can be watched here: https://www.youtube.com/watch?v=-smmdOz9gIU The manuscript of Negri’s talk was published as part of a conference volume. It is reprinted based on a Creative Commons licence. Acknowledgement: Negri, Antonio. 2019. The Appropriation of Fixed Capital: A Metaphor? In Digital Objects, Digital Subjects: Interdisciplinary Perspectives on Capitalism, Labour and Politics in the Age of Big Data, edited by David Chandler and Christian Fuchs, 205-214. London: University of Westminster Press. DOI: https://doi.org/10.16997/book29.r. License: CC-BY-NC-ND 4.0. The original article was published in Italian in the journal EuroNomade and translated into English with permission: https://www.euronomade.info/appropriazione-di-capitale-fisso-una-metafora/

Acknowledgments

The CEC and ICMC Boards wish to thank our supporters and sponsors who have contributed to the 2023 CEC/ICMC Conference. CONFERENCE SPONSORS AND ADVERTISERS • Aerospace Fabrication and Materials • Cryofab, Inc • Cryogenic US LLC • Cryomech, Inc • Danaher Cryogenics LTD • FAMU-FSU College of Engineering • GenH2 • ICEoxford • National High Magnetic Field Laboratory • Scientific Instruments • Sumitomo (SHI) Cryogenics of America, Inc. • Texas Center for Superconductivity at the University of Houston EXHIBITORS • Ability Engineering Technology, Inc. • Aerospace Fabrication and Materials • Air Liquide Advanced Technologies • attocube systems Inc. • Barber-Nichols • Celadon Systems Inc. • Cryofab, Inc. • Cryomagnetics, Inc. • Cryomech, Inc. • CryoTechnics • CryoWorks • Cryoworld BV • Danaher Cryogenics LTD • FABRUM • FormFactor Inc. • Fujikura Ltd. • Honeywell • Hyper Tech • ICEoxford • Iris Technologies • Lake Shore Cryotronics • Lihan Cryogenics Co., Ltd. • Linde Kryotechnik AG • Omegaflex • Ratheon Technologies Research Center • Scientific Instruments • Stöhr Armaturen GmbH & Co.KG • Sumitomo (SHI) Cryogenics of America, Inc. • Sunpower, Inc. • Vacree Technologies Co., Ltd. • WSU HYPER Lab Producing the Open Access IOP Conference Series: Materials Science and Engineering (MSE) requires the dedicated effort of many individuals. The quality of the publication relies on the dedication of those who took time from their busy schedules to review and edit papers. The Boards wish to specifically acknowledge the efforts of Centennial Conferences for their editorial support, and the chief technical editors, John Weisend (CEC) and Balu Balachandran (ICMC). Their contributions to ensure a quality publication in a timely manner are greatly appreciated. The chief technical editors are indebted to the individual technical sub-editors for their time spent with reviewers and authors to get the final manuscripts ready for publication. The Boards also wish to thank all students and post-doctoral researchers from a number of universities for their service with the initial format checking of the papers submitted for peer review.CEC/ICMC 2023 was managed by Paula Pair and Centennial Conferences. Recognizing this is a tremendous team effort, the Boards would especially acknowledge, in addition to Paula, all her staff – Annett Cady, Andrea and Paul Crangle, Brion Jacobs, Andrew Kahl, Carrie Lian, Katherine Neilson, Alicia Orcutt, Sydney Pair, and Christina Tomhave – for the fantastic job they did wonderfully.We also would like to recognize the effort and dedication of the attendees in preparing their presentations and papers, and showing the professionalism and enthusiasm that makes the CEC/ICMC such a great Conference time after time.

Acknowledgments

The CEC and ICMC Boards wish to thank our supporters and sponsors who have contributed to the 2023 CEC/ICMC Conference. CONFERENCE SPONSORS AND ADVERTISERS • Aerospace Fabrication and Materials • Cryofab, Inc • Cryogenic US LLC • Cryomech, Inc • Danaher Cryogenics LTD • FAMU-FSU College of Engineering • GenH2 • ICEoxford • National High Magnetic Field Laboratory • Scientific Instruments • Sumitomo (SHI) Cryogenics of America, Inc. • Texas Center for Superconductivity at the University of Houston EXHIBITORS • Ability Engineering Technology, Inc. • Aerospace Fabrication and Materials • Air Liquide Advanced Technologies • attocube systems Inc. • Barber-Nichols • Celadon Systems Inc. • Cryofab, Inc. • Cryomagnetics, Inc. • Cryomech, Inc. • CryoTechnics • CryoWorks • Cryoworld BV • Danaher Cryogenics LTD • FABRUM • FormFactor Inc. • Fujikura Ltd. • Honeywell • Hyper Tech • ICEoxford • Iris Technologies • Lake Shore Cryotronics • Lihan Cryogenics Co., Ltd. • Linde Kryotechnik AG • Omegaflex • Ratheon Technologies Research Center • Scientific Instruments • Stöhr Armaturen GmbH & Co.KG • Sumitomo (SHI) Cryogenics of America, Inc. • Sunpower, Inc. • Vacree Technologies Co., Ltd. • WSU HYPER Lab Producing the Open Access IOP Conference Series: Materials Science and Engineering (MSE) requires the dedicated effort of many individuals. The quality of the publication relies on the dedication of those who took time from their busy schedules to review and edit papers. The Boards wish to specifically acknowledge the efforts of Centennial Conferences for their editorial support, and the chief technical editors, John Weisend (CEC) and Balu Balachandran (ICMC). Their contributions to ensure a quality publication in a timely manner are greatly appreciated. The chief technical editors are indebted to the individual technical sub-editors for their time spent with reviewers and authors to get the final manuscripts ready for publication. The Boards also wish to thank all students and post-doctoral researchers from a number of universities for their service with the initial format checking of the papers submitted for peer review.CEC/ICMC 2023 was managed by Paula Pair and Centennial Conferences. Recognizing this is a tremendous team effort, the Boards would especially acknowledge, in addition to Paula, all her staff – Annett Cady, Andrea and Paul Crangle, Brion Jacobs, Andrew Kahl, Carrie Lian, Katherine Neilson, Alicia Orcutt, Sydney Pair, and Christina Tomhave – for the fantastic job they did wonderfully.We also would like to recognize the effort and dedication of the attendees in preparing their presentations and papers, and showing the professionalism and enthusiasm that makes the CEC/ICMC such a great Conference time after time.

New phase 1 SURPASS trial cohort: Early-line ADP-A2M4CD8 T-cell receptor T-cell therapy plus pembrolizumab in urothelial carcinoma.

TPS708 Background: ADP-A2M4CD8 T-cell receptor (TCR) T-cell therapy consists of autologous CD4+ and CD8+ T-cells genetically modified to target melanoma-associated antigen A4 (MAGE-A4) in patients (pts) with advanced cancers who are human leukocyte antigen A*02 eligible. In the late-line setting, ADP-A2M4CD8 monotherapy has demonstrated an acceptable benefit-to-risk profile and clinical responses across multiple tumor types in the ongoing Phase 1 SURPASS trial (NCT04044859). As of November 23, 2022, there were encouraging signs of antitumor activity in the 7 pts with advanced urothelial carcinoma (UC) treated in SURPASS, with best overall responses of 1 complete response, 3 partial responses, and 3 stable disease, giving an overall response rate of 57.1% and a disease control rate of 100% (Aggen DH. et al., Poster 517, ASCO-GU 2023; San Francisco, CA, USA). Furthermore, inhibiting immunosuppressive pathways may enhance antitumor activity. Thus, a new SURPASS cohort consisting of early-line ADP-A2M4CD8 TCR T-cell therapy combined with pembrolizumab in participants with UC has been opened. Methods: A dedicated UC cohort will enroll ≤15 pts with unresectable locally advanced or metastatic UC who have received first-line cisplatin-based standard-of-care (SOC) chemotherapy and are either currently receiving second-line SOC pembrolizumab or have received avelumab maintenance therapy and no second-line therapy. Key eligibility criteria include >30% of tumor cells expressing MAGE-A4 (≥2+ by immunohistochemistry); positivity for HLA-A*02:01, 02:02, 02:03, or 02:06 alleles; measurable disease per RECIST v1.1 prior to lymphodepletion; and ECOG performance status of 0 or 1. T-cells are collected by leukapheresis, transduced with a lentiviral vector expressing the MAGE-A4-specific TCR and an additional CD8α co-receptor designed to increase functionality of CD4+ T-cells, and expanded ex vivo. Pts receive lymphodepletion chemotherapy consisting of cyclophosphamide 600 mg/m2/day for 3 days and fludarabine 30 mg/m2/day for 4 days followed by ADP-A2M4CD8 infusion (1x109 to 10x109 transduced T-cells) and subsequent pembrolizumab 400 mg (administered every six weeks for ≤2 years, until unacceptable toxicity or disease progression). Primary and secondary endpoints include evaluation of adverse events (AEs), serious AEs, AEs of special interest, and overall response rate per RECIST v1.1 by investigator review, respectively. Trial registration number: NCT04044859. Editorial acknowledgement:This study is sponsored by Adaptimmune (Philadelphia, PA, USA). Writing and editorial support was from Excel Scientific Solutions (Fairfield, CT, USA); funding was provided by Adaptimmune. Clinical trial information: NCT04044859 .

No additional risk of congenital anomalies after first-trimester dydrogesterone use: a systematic review and meta-analysis.

No additional risk of congenital anomalies after first-trimester dydrogesterone use: a systematic review and meta-analysis.

Pathways for Diagnosing and Treating CKD-Associated Pruritus: A Narrative Review.

Chronic kidney disease (CKD)-associated pruritus is a common, persistent, and distressing itch experienced by patients across the CKD spectrum. Although the disorder is associated with adverse outcomes and poor health-related quality of life, it remains underdiagnosed and undertreated. The purpose of this narrative review is to offer health care providers guidance on how to effectively identify, assess, and treat patients with CKD-associated pruritus, with the goal of reducing symptom burden and improving patient-important outcomes, such as quality of life (QoL). A panel of nephrologists and researchers from across Canada and the United States was assembled to develop this narrative review based on the best available data, current treatment guidelines, and their clinical experiences. A panel of nephrologists who actively care for patients with pruritus receiving dialysis from across Canada was assembled. Two researchers from the United States were also included based on their expertise in the diagnosis and management of CKD-associated pruritus. Throughout Spring 2023, the panel met to discuss key topics in the identification, assessment, and management of CKD-associated pruritus. Panel members subsequently developed summaries of the pertinent information based on the best available data, current treatment guidelines, and added information on their own clinical experiences. In all cases, approval of the article was sought and achieved through discussion. This narrative review provides pragmatic guidance addressing: (1) methods for screening CKD-associated pruritus, (2) assessing severity, (3) management of CKD-associated pruritus, and (4) suggested areas for future research. The panel developed a 3-pillar framework for proactive assessment and severity scoring in CKD-aP: systematic screening for CKD-associated pruritus (pillar 1), assessment of pruritus intensity (pillar 2), and understanding the impact of CKD-associated pruritus on the patient's QoL (pillar 3). Management of CKD-associated pruritus can include ensuring optimization of dialysis adequacy, achieving mineral metabolism targets (ie, calcium, phosphate, and parathyroid hormone). However, treatment of CKD-associated pruritus usually requires additional interventions. Patients, regardless of CKD-associated pruritus severity, should be counseled on adequate skin hydration and other non-pharmacological strategies to reduce pruritus. Antihistamines should be avoided in favor of evidence-based treatments, such as difelikefalin and gabapentin. A formal systematic review (SR) of the literature was not undertaken, although published SRs were reviewed. The possibility for bias based on the experts' own clinical experiences may have occurred. Key takeaways are based on the current available evidence, of which head-to-head clinical trials are lacking. This work was funded by an arm's length grant from Otsuka Canada Pharmaceutical Inc. (the importer and distributer of difelikefalin in Canada). LiV Medical Education Agency Inc. provided logistical and editorial support.

Appreciation of Editorial Board, Reviewers, Authors and Support Staff

Appreciation of Editorial Board, Reviewers, Authors and Support Staff

TABLET: Relative bioavailability and bioequivalence study of niraparib tablets and capsules in patients with advanced solid tumors.

e17603 Background: Niraparib is a poly (ADP-ribose) polymerase inhibitor, approved as a maintenance treatment (tx) for patients (pts) with advanced ovarian cancer and under investigation in solid tumors, available in 100 mg capsules (starting dose: 200 or 300 mg/day). Compared with capsules, tablets have improved stability in hot and humid conditions. This study assessed the relative bioavailability (BA; Stage 1 [S1]) and bioequivalence (BE; Stage 2 [S2]) between niraparib tablets and capsules. Methods: This was a US, open-label, multicenter, single-cohort, randomized-sequence study with an optional extension phase. Eligible pts were ≥18 years, had histologically/cytologically confirmed advanced solid tumors (metastatic or local), disease progression despite standard therapy (if available), and ECOG performance scores of 0–2. Pts were dosed 1x300 mg tablet or 3x100 mg capsules then crossed over to the other tx after full washout. Pharmacokinetic (PK) parameters were assessed up to 168 hours post-niraparib dose; safety was assessed throughout and for 30 days after last dose (90 days for serious adverse events). A comparison of the log-transformed PK parameters (maximum observed plasma concentration [Cmax], area under the plasma concentration–time curve from time 0 to time of the last quantifiable concentration [AUC0–t] and from time 0 extrapolated to infinity [AUC0–∞]) was carried out to evaluate the formulations using a linear mixed-effects model with fixed effects for sequence, period, and tx and random effect for pt nested within sequence. Results: Pts in both stages completed study drug and washout/PK periods and had sufficient PK samples to estimate PK parameters in both periods. In S1 (n=29), a comparable BA performance of both formulations was demonstrated; the 90% confidence intervals (CI) of the geometric least square means (LSM) for Cmax, AUC0–t, and AUC0–∞ for tablet/capsule were within prespecified 0.80–1.25 limits (intra-pt variability: 12.4–21.9%). An initial 7-day washout period between PK assessments was extended to 14 days in S2 due to significant carryover reported in 6 pts in S1. In S2 (n=108), niraparib PK characteristics were similar following dosing with tablet or capsule (Table); LSM ratios of the key parameters were close to unity and 90% CI for the ratio of Cmax, AUC0–t, and AUC0–∞ were within prespecified 0.80–1.25 limits required to demonstrate BE. No new safety signals were reported. Conclusions: Both niraparib formulations were bioequivalent and can be used interchangeably. Editorial support was provided by Fishawack Health, funded by GSK. Clinical trial information: NCT03329001 . [Table: see text]

Real-world overall survival in second-line maintenance niraparib monotherapy vs active surveillance in BRCA wild-type patients with recurrent ovarian cancer.

5592 Background: The Phase 3NOVA trial assessed niraparib versus placebo as a maintenance treatment (tx) for patients (pts) with recurrent ovarian cancer (OC) who were platinum-sensitive after ≥2 regimens; progression-free survival was the primary endpoint and overall survival (OS) was a secondary endpoint (NCT01847274). The aim of this real-world study was to compare OS in a breast cancer gene wild-type ( BRCAwt) population of pts with recurrent OC and who received second-line maintenance (2Lm) niraparib monotherapy or were under active surveillance (AS). Methods: This study used the US nationwide Flatiron Health de-identified electronic health record (EHR)-derived database. Pts diagnosed with epithelial OC between 1Jan2011–31May2021 who completed 2L therapy between 1Jan2017–2Mar2022 were eligible for inclusion. Pts were BRCAwt, had an ECOG PS score 0–1, epithelial histology, and platinum-sensitive disease with ≥6 months between end of first-line tx and start of 2L tx. Pts were assigned to 2Lm niraparib or AS cohorts based on their management following 2L non-maintenance therapy (≤120 days). Follow-up was measured from the index date (end of 2L non-maintenance therapy) until end of study (31May2022), last activity, or death, whichever came first. A target trial emulation cloned inverse probability of censoring weighting (IPCW) methodology was selected a priori to minimize bias. IPCW median OS and hazard ratios (HR) for 2Lm versus AS were estimated with Kaplan-Meier curves and Cox regression models. Results: Overall, 266 BRCAwt pts were included and received niraparib 2Lm (N=123) or were under AS (N=143). Across 2Lm and AS cohorts, prior to cloning and IPCW, 23.6% and 34.3% of pts were aged ≥75 years, and 26.0% and 16.8% had an EHR value for race as other than White, respectively. The majority of pts were from community practice (80.5% and 90.2%, respectively), had serous OC (79.7% and 81.1%) and had Stage III disease (53.7% and 60.8%). Homologous recombination deficiency status was unknown for 92.7% and 86.0% of pts in 2Lm and AS cohorts, respectively. Median follow-up for 2Lm and AS cohorts was 16.8 (Quartile [Q] 1, Q3: 10.4, 28.7) and 10.2 (Q1, Q3: 4.1, 23.7) months, respectively. IPCW median OS was 28.1 (95% confidence interval [CI]: 22.5, 43.2) and 21.5 (95% CI: 14.7, 27.0) months (HR: 0.63 [95% CI: 0.45, 0.88]) for niraparib 2Lm and AS cohorts, respectively and survival rates at 24 months were 58.2% (95% CI: 47.5, 67.6) and 46.1% (95% CI: 33.6, 57.7). Conclusions: This analysis provides real-world data on OS among pts with OC receiving niraparib 2Lm or under AS in the 2L setting following chemotherapy. Funding: GSK study (219306). Editorial support was provided by Fishawack Health, funded by GSK.

LBA02-09 EMBARK: A Phase 3 Randomized Study of Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in High-risk Biochemically Recurrent Prostate Cancer

LBA02-09 EMBARK: A Phase 3 Randomized Study of Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in High-risk Biochemically Recurrent Prostate Cancer

Media Capture and Journalism as Emotional Labor: How Do Media Professionals Manage Bureaucratic Violence in the Kurdistan Region of Iraq?

ABSTRACT This paper focuses on the (in)direct tools of governmental bureaucracy used to control journalistic work in the Kurdistan Region of Iraq (KRI). It calls for understanding media capture not only through structural-level consequences, but also through the methods used to create an environment of instability and unsafety. To make sense of these processes, and how they are experienced and negotiated by journalists, this paper combines scholarship on the emotional labor of journalism with scholarship on processes of media capture in deeply restrictive environments. The mixed-methods approach aims first to uncover structural conditions of media capture in the KRI through a document analysis of 21 public reports published by the Kurdistan Journalists’ Syndicate (KJS) and the Metro Center for Journalists’ Rights and Advocacy (MC) between 2014 and 2020. Second, it aims to reveal how journalists and editors-in-chief from diverse media organizations manage and negotiate these chronic conditions of precarity and instability, through 15 semi-structured in-depth interviews. The results show multiple strategies that have been developed by journalists and editors to mitigate or acclimate direct and indirect bureaucratic violence (e.g., editorial support, socialization skills and networks, understanding of unspoken and unwritten rules, etc.)

Abstract GS2-01: GS2-01 Trastuzumab deruxtecan vs physician’s choice in patients with HER2+ unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine: primary results of the randomized, phase 3 study DESTINY-Breast02

Abstract In DESTINY-Breast01 (NCT03248492) and DESTINY-Breast03 (NCT03529110), trastuzumab deruxtecan (T-DXd) demonstrated unprecedented activity in patients (pts) with HER2+ (immunohistochemistry 3+; immunohistochemistry 2+/in situ hybridization+) advanced metastatic breast cancer (mBC), leading to regulatory approvals in several countries for HER2+ unresectable/mBC after a prior anti–HER2-based regimen. DESTINY-Breast02 (NCT03523585) is a phase 3 trial of T-DXd vs treatment of physician’s choice (TPC) in patients with centrally confirmed HER2+ mBC previously treated with trastuzumab emtansine (T-DM1). It acts as a confirmatory study for the pivotal phase 2 DESTINY-Breast01 trial. Here we report the primary results of DESTINY-Breast02. Methods: Pts with HER2+ mBC were randomized 2:1 to receive T-DXd or TPC (trastuzumab + capecitabine or lapatinib + capecitabine) and stratified by hormone receptor (HR) status (HR+/HR-), prior pertuzumab treatment, and history of visceral disease. The primary endpoint of this time-driven primary analysis was progression-free survival (PFS) as determined by blinded independent central review (BICR). The powered secondary endpoint was overall survival (OS). Other secondary endpoints included confirmed objective response rate (ORR) by BICR, duration of response (DoR) by BICR, PFS by investigator assessment, safety, and others. Results: 608 pts were randomized to receive T-DXd (n = 406) or TPC (n = 202). Pts receiving T-DXd and TPC had a median age of 54.2 years (range, 22.4-88.5 years) and 54.7 years (range, 24.7-86.5 years), respectively, with a median of 2 (range, 0-10 and range,1-8) prior lines of systemic therapy (excluding hormone therapy) in the metastatic setting. Median treatment duration was 11.3 mo in the T-DXd arm and ~4.5 mo in the TPC arm. Efficacy and safety results are shown in the table below. T-DXd significantly improved PFS (HR, 0.36; 95% CI, 0.28-0.45; P <0.000001) and OS (HR, 0.66; 95% CI, 0.50-0.86; P = 0.0021) compared with TPC. Confirmed ORR was 69.7% (14% complete response) with T-DXd and 29.2% (5.0% complete response) with TPC. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 52.7% and 44.1% of pts receiving T-DXd and TPC, respectively. Adjudicated drug-related interstitial lung disease (ILD) occurred in 10.4% of pts with T-DXd vs 0.5% of pts with TPC. In pts receiving T-DXd, most ILD cases (88.1%) were grade 1/2 and grade 5 ILD was reported in 2 (0.5%) pts. Conclusions: Results from DESTINY-Breast02 confirmed the clinical benefit and superiority of T-DXd over conventional chemotherapy-based regimens in pts with HER2+ mBC previously treated with T-DM1, as evidenced by significant and clinically meaningful improvements in PFS and OS. These data, together with earlier reported results from the DESTINY-Breast03 study of T-DXd vs T-DM1 solidify T-DXd as an optimal treatment option in pts with progressive HER2+ mBC across broad settings. Editorial Acknowledgment Under guidance of the authors, assistance in medical writing and editorial support was provided by Caylin Bosch, PhD, of ApotheCom, and was funded by Daiichi Sankyo. Funding This study was funded by Daiichi Sankyo and AstraZeneca. Table. Summary of Efficacy and Safety Results for T-DXd and TPC in Patients With HER2+ mBC Previously Treated With T-DM1 Citation Format: Ian Krop, Yeon H. Park, Sung-Bae Kim, Giuliano Borges, Sercan Aksoy, Joaquin Gavila Gregori, Rebecca Roylance, Elgene Lim, Rinat Yerushalmi, Flora Zagouri, Francois P. Duhoux, Tanja Fehm, Toshimi Takano, Anton Egorov, Iris Wu, Jillian Cathcart, Changan Chu, Fabrice Andre. GS2-01 Trastuzumab deruxtecan vs physician’s choice in patients with HER2+ unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine: primary results of the randomized, phase 3 study DESTINY-Breast02 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS2-01.

Abstract HER2-13: HER2-13 Proficiency assessment of HER2-low breast cancer scoring with the Ventana PATHWAY 4B5 and Dako HercepTest HER2 assays and the impact of pathologist training

Abstract Background: Based on the results of the DESTINY-Breast04 study, the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd) and the Ventana PATHWAY 4B5 companion diagnostic were recently approved by the US Food and Drug Administrated for the treatment and identification of patients with HER2-low (IHC2+/ISH- or IHC1+) (Modi et al. N Engl J Med 2022). The efficacy of T-DXd in HER2-low mBC highlights the need to distinguish lower ranges of HER2 IHC expression, which has been reported to be more challenging than scoring high HER2 expression (Fernandez et al. JAMA Oncol 2022). Here we report on current real-world HER2-low interpretation proficiency and the impact of training for participating pathologists in HER2-low scoring. Methods: Pathologists from laboratories across the US, EU, Japan, Australia, and Brazil were invited to use a digital pathology platform (Pathotrainer) to interpret HER2 digital images using ASCO/CAP 2018 scoring criteria. Two whole-slide imaging sample sets of representative study cases were compiled for Ventana PATHWAY 4B5 or Dako HercepTest (HcT) stained tumors. Another sample set (n = 25) was developed for a 4 hour virtual training session based on the ASCO/CAP 2018 guideline with some practical considerations. A steering committee (SC) of 8 pathology experts was formed to guide the study. Pathologists’ score was compared with a reference score as determined by independent review of 3 experts in HER2 pathology. Paired study cases (n = 14) considered challenging due to difficult-to-interpret staining patterns were reevaluated by the SC members. Concordance and efficacy of training were measured by Cohen’s weighted kappa (κ) coefficient, overall rater agreement (ORA), and receiver operating characteristic curve statistics. The primary endpoint was real-world concordance and ORA. The secondary endpoints were post-training concordance and ORA and correct identification of HER2 IHC 0 and HER2-low. Results: Pre-training baseline or real-world scores were taken by 77 pathologists in 14 countries (n = 49 for 4B5, n = 28 for HcT) and 74 pathologists completed post-training scores (n = 48 for 4B5, n = 26 for HcT). HER2 scoring proficiency of pathologists was high for both assays when assessed on ASCO/CAP binary HER2-negative and -positive status, irrespective of training (4B5: κ = 0.96, ORA =98.9.%; HcT: κ = 0.84, ORA = 94.3%) Concordance per ORA for the new 3-tier classification (HER2 IHC 0 vs HER2-low [IHC 2+/ISH- or IHC 1+] vs HER2-positive [IHC 3+ or IHC 2+/ISH+]) was greater than 80% for both assays at baseline and after training (see Table). In a subgroup analysis assessing training effect for 4B5 assay, concordance rates for HER2 IHC 0 were 74.6% at baseline and 89.2% after training (P < 0.001), and for HER2-low, NPA was 80.6% before and 91.1% after training (P < 0.001); there were no statistically significant changes after training for HcT (data not shown). Conclusions: Results from this real-world global study demonstrate that overall score concordance with a new category of HER2-low was above the 80% ORA benchmark for both 4B5 and HcT and is higher than previously reported (Fernandez et al. JAMA Oncol 2022). These data demonstrate pathologists’ ability to achieve an acceptable level of accuracy for identifying HER2 IHC 0 and HER2-low patients even after short-term training; however, additional training techniques and experience are needed to further improve accuracy. Acknowledgment Judy Yu, a former AstraZeneca employee, provided expertise and technical insights to support the study. Editorial Acknowledgment Under guidance of the authors, assistance in medical writing and editorial support was provided by Toinette Labuschagné, MSc, of ApotheCom, and was funded by Daiichi Sankyo. Funding This study was funded by Daiichi Sankyo and AstraZeneca. Table. Summary of Pathologist Concordance and Interobserver Variability Citation Format: Josef Rüschoff, Alexander Penner, Ian O. Ellis, M. Elizabeth H. Hammond, Annette Lebeau, Robert Y. Osamura, Frédérique Penault-Llorca, Federico Rojo, Neil Atkey, Andreas H. Scheel, Corrado D´Arrigo, Hans-Ulrich Schildhaus, Akira Moh, Chirag Desai, Giuseppe Viale. HER2-13 Proficiency assessment of HER2-low breast cancer scoring with the Ventana PATHWAY 4B5 and Dako HercepTest HER2 assays and the impact of pathologist training [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr HER2-13.

Abstract GS2-02: GS2-02 Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated survival results of the randomized, phase 3 study DESTINY-Breast03

Abstract Background: Trastuzumab deruxtecan (T-DXd) is approved in the United States and European Union for use in patients (pts) with HER2+ unresectable/metastatic breast cancer (mBC) after ≥1 prior anti–HER2 regimen(s). Approval was based on the randomized, multicenter, open-label, phase 3 DESTINY-Breast03 study (NCT03529110), in which T-DXd demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with trastuzumab emtansine (T-DM1). At the primary interim analysis (data cutoff May 21, 2021), the risk of disease progression or death was reduced by 72% with T-DXd (P < 0.001; Cortes et al. N Engl J Med 2022). Overall survival (OS) data were immature for both treatment groups; although the prespecified cutoff for significance was not reached (NR), a trend toward benefit with T-DXd was observed. With further follow-up, we report results from the prespecified OS analysis of DESTINY-Breast03 (data cutoff July 25, 2022), including updated efficacy and safety. Methods: Pts with HER2+ mBC previously treated with trastuzumab and a taxane in either the metastatic setting or (neo)adjuvant setting with progression within 6 mo of therapy, who could have received pertuzumab, were randomly assigned 1:1 to receive T-DXd 5.4 mg/kg every 3 weeks (Q3W) or T-DM1 3.6 mg/kg Q3W until disease progression. The primary endpoint was PFS by blinded independent central review (BICR). The key secondary endpoint was OS (80% powered at 2-sided significance level of 5%); other secondary endpoints included objective response rate (ORR), duration of response (DoR), PFS based on investigator assessment, and safety. Results: 524 pts received either T-DXd (n = 261) or T-DM1 (n = 263). As of the updated data cutoff, median duration of study follow-up was 28.4 mo (range, 0.0-46.9 mo) for T-DXd and 26.5 mo (range, 0.0-45.0 mo) for T-DM1. Median treatment duration was 18.2 mo (range, 0.7-44.0 mo) for T DXd and 6.9 mo (range, 0.7-39.3 mo) for T-DM1. The risk of death was reduced by 36% (HR, 0.64; P = 0.0037) with T-DXd; median OS (mOS) was NR (95% CI, 40.5 mo-not evaluable [NE]), with 72 (27.6%) OS events, for T-DXd vs NR (95% CI, 34.0 mo-NE), with 97 (36.9%) OS events, for T-DM1. Landmark 12-mo OS rate was 94.1% (95% CI, 90.4-96.4) for T-DXd vs 86.0% (95% CI, 81.1-89.8) for T-DM1; 24-mo OS rate was 77.4% (95% CI, 71.7-82.1) for T-DXd vs 69.9% (95% CI, 63.7-75.2) for T-DM1. The P value for OS crossed the prespecified boundary (P = 0.013) and was statistically significant. mPFS by BICR was 28.8 mo (95% CI, 22.4-37.9 mo) with T-DXd, compared with 6.8 mo (95% CI, 5.6-8.2 mo) with T-DM1; HR, 0.33; nominal P < 0.000001. Key efficacy and safety results are shown in the table. Grade ≥3 treatment-emergent adverse events were experienced by 56.4% of T-DXd-treated pts and 51.7% of T DM1-treated pts. Drug-related interstitial lung disease/pneumonitis, as evaluated by an independent adjudication committee, was experienced by 39 pts (15.2%) in the T-DXd arm and 8 pts (3.1%) in the T DM1 arm; no adjudicated drug-related grade 4 or 5 events were observed in pts who received T-DXd. Conclusions: Updated results confirm the superiority of T-DXd compared with T-DM1 for pts with HER2+ mBC previously treated with an anti-HER2 therapy, with highly clinically meaningful and statistically significant benefit in OS and PFS and a manageable safety profile with longer treatment duration. Editorial Acknowledgment Under the guidance of authors, assistance in medical writing and editorial support was provided by Laura Halvorson, PhD, and Rachel Hood, PhD, of ApotheCom, and was funded by Daiichi Sankyo. Funding This study was funded by Daiichi Sankyo and AstraZeneca. Table. Summary of Efficacy Results for T-DXd and T-DM1 Citation Format: Sara Hurvitz, Roberto Hegg, Wei-Pang Chung, Seock-Ah Im, William Jacot, Vinod Ganju, Joanne Win Yang Chiu, Binghe Xu, Erika Hamilton, Srinivasan Madhusudan, Hiroji Iwata, Sevilay Altintas, Jan-Willem Henning, Giuseppe Curigliano, José Manuel Pérez-García, Anton Egorov, Yali Liu, Jillian Cathcart, Shahid Ashfaque, Javier Cortés. GS2-02 Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated survival results of the randomized, phase 3 study DESTINY-Breast03 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS2-02.

Abstract P1-11-01: Trastuzumab deruxtecan vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: Subgroup analyses from DESTINY-Breast04

Abstract Background: DESTINY-Breast04 demonstrated that the HER2 targeting antibody–drug conjugate trastuzumab deruxtecan (T-DXd) significantly prolonged progression-free survival (PFS) and overall survival (OS) vs treatment of physician’s choice (TPC) in patients (pts) with HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization negative) metastatic breast cancer (mBC) in pts in the hormone receptor−positive (HR+) cohort and all pts (HR+ and HR-; median PFS, 9.9 vs 5.1 months [mo], hazard ratio: 0.50; median OS, 23.4 vs 16.8 mo, hazard ratio: 0.64; both P < 0.0001; Modi et al. N Engl J Med 2022). Objective response rate (ORR) with T-DXd was ≥50% across cohorts. These subgroup analyses examine pt history and disease characteristics that may correlate with response to therapy. Methods: N = 557 pts with centrally confirmed HER2-low mBC were randomized 2:1 to T-DXd or TPC. Randomization was stratified by HER2 status (IHC 1+ vs 2+), 1 vs 2 prior lines of chemotherapy, and HR+ (with vs without prior treatment with cyclin-dependent kinase 4/6 inhibitor [CDK4/6i]) vs HR−. With the exception of the PFS and OS analyses by prior CDK4/6i use, all other described efficacy analyses were assessed post-hoc. Results: Benefit of T-DXd vs TPC was consistent in pts with or without prior CDK4/6i use (Table 1). Pts with high disease burden (ie, ≥3 metastatic sites) also benefited from T-DXd vs TPC (Table 2). There was a small subgroup (n = 22) among all pts (HR+ [n = 18] and HR− disease [n = 4]) with rapid progression prior to enrollment (disease progression within 6 mo of concluding a prior course of chemotherapy in early breast cancer). T-DXd showed responses in 7/14 (50%) pts in this subgroup vs 0/8 with TPC; this subgroup also had prolonged median PFS with T-DXd vs TPC (Table 3). Efficacy data for HER2 IHC 1+ vs 2+ and prior chemotherapy subgroups will be presented. Median OS was not reached for many subgroups (insufficient events in each group [data not shown]); however, subgroups in general showed OS benefit consistent with the primary analysis. With T-DXd, rates of interstitial lung disease/pneumonitis were similar in pts with/without prior CDK4/6i use. Conclusions: T-DXd treatment for HER2-low mBC in the phase 3 study DESTINY-Breast04 showed consistent efficacy independent of disease burden, prior CDK4/6i treatment, or rapid progression status. ILD is an important identified risk and requires proactive monitoring and management. These data continue to support the use of T-DXd as the new standard of care across subgroups of pts with HER2-low mBC. Editorial Acknowledgment Under guidance of the authors, assistance in medical writing and editorial support was provided by Eileen McIver, PhD, and Soniya Patel, PhD, of ApotheCom, and was funded by Daiichi Sankyo. Funding This study was funded by Daiichi Sankyo and AstraZeneca. Table 1. Efficacy by Prior CDK4/6i Treatment in Pts With HER2-Low Breast Cancer, HR+ Cohort. Table 2. Efficacy by Disease Burdena in Pts With HER2-Low Breast Cancer, ITT. Table 3. Efficacy by Rapid Progressor Statusa in Pts With HER2-Low Breast Cancer, ITT. Citation Format: Nadia Harbeck, Shanu Modi, William Jacot, Toshinari Yamashita, Joo Hyuk Sohn, Maria Vidal, Junji Tsurutani, Naoto T. Ueno, Aleix Prat, Naoki Niikura, Binghe Xu, Hope Rugo, Konstantinos Papazisis, Javier Cortés, Ian Krop, Dhiraj Gambhire, Lotus Yung, Yibin Wang, Jasmeet Singh, David Cameron. Trastuzumab deruxtecan vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: Subgroup analyses from DESTINY-Breast04 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-01.

Budget impact of introducing once-every-6-months paliperidone palmitate in US health care plans.

BACKGROUND: In the United States, most patients with schizophrenia have Medicaid coverage. Antipsychotic treatments are the cornerstone of schizophrenia management; most patients are treated with daily oral antipsychotics but struggle with medication adherence. Evidence suggests that medication adherence is inversely correlated with dosing frequency. Once-monthly paliperidone palmitate (PP) has been demonstrated to improve adherence compared with oral antipsychotics; transitioning to once-every-3-months PP (PP3M) further improved adherence. In 2021, once-every-6-months PP (PP6M) was approved by the US Food and Drug Administration to provide even longer between-dose intervals. Public health stakeholders who aim to improve medication adherence are interested in understanding how introducing PP6M to the formulary will impact the budget. OBJECTIVE: To evaluate the budget impact of introducing PP6M to the formulary from the perspectives of a hypothetical US multistate health care payer and state Medicaid programs using California, Georgia, and Ohio as examples. METHODS: The budget impact model was developed from a payer perspective, comparing the reference scenario (without PP6M in the market) with a new scenario (with PP6M). The study population included patients with schizophrenia who were eligible to receive PP6M. Market shares were assigned to the reference and new market scenarios. Efficacy was measured by the relative risk of relapse while receiving treatment. Adherence effects were included in the model and affected costs of treatment and relapse rates. A deterministic 1-way sensitivity analysis was performed. RESULTS: Base-case results for a multistate payer with 1 million members demonstrate that adding PP6M to the market results in total incremental plan-level costs ranging from $7,747 in year 1 to $11,501 in year 5. Increased drug costs were offset by administration and relapse cost savings ($105 and $881 in year 5, respectively). The average incremental cost per treated patient per year was stable at $180.06 for each year, and the incremental cost per member per month stayed below $0.01 for each year. The results of the model from the state-level Medicaid scenarios are broadly similar to those of the multistate base-case perspective. The 1-way sensitivity analysis demonstrated the model is most sensitive to the per-package costs of PP6M and PP3M, along with the proportion of patients fully adherent with PP3M. CONCLUSIONS: The budget impact of introducing PP6M as a treatment option is minimal. With the expected cost offsets from reduced administration and relapse costs due to adherence benefits, these results suggest that PP6M can be a viable treatment option from a clinical and a budgetary perspective. DISCLOSURES: This study was funded by Janssen Scientific Affairs, LLC. The study sponsor provided funds to Xcenda and ApotheCom for medical writing, editorial support, and submission of the manuscript. Hilary Phelps was an employee of Janssen Global Services, LLC, at the time of the development and finalization of the manuscript. Alex Keenan is an employee of Janssen Global Services, LLC, and holds stock in Johnson & Johnson, Inc. Dee Lin and Carmela Benson are employees of Janssen Scientific Affairs, LLC, and hold stock in Johnson & Johnson, Inc. Aditya Raju was an employee of Xcenda at the time of the development and finalization of the manuscript, and Danmeng Huang is an employee of Xcenda, a health care consulting firm that was contracted by Janssen Scientific Affairs, LLC. Chih-Yuan Cheng is an employee of Janssen NV.

Letter in reply: aletter to the editor commenting on the recent publication by AY Avidan and CA Kushida.

Letter in reply: aletter to the editor commenting on the recent publication by AY Avidan and CA Kushida.