bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amivantamab plus chemotherapy vs chemotherapy as first-line treatment among patients with EGFR exon 20 insertion–mutated advanced non-small cell lung cancer (NSCLC): PAPILLON Chinese subgroup analysis.
Authors: Tang Ke-Jing , Liu Baogang , Yao Yu , Zhao Yanqiu , Zhou Jianying , Sun Ping , Wang Donglin , Lv Dongqing , Wang Huijie , Hu Yi , Li Qiang , Song Yujiao , Gao Grace , Wang Liyun , Agrawal Trishala , Bhattacharya Archan , Baig Mahadi , Lorenzini Patricia A , Wortman-Vayn Honeylet , Zhou Caicun 
Published: June 2024

8606 Background: Amivantamab (Ami) is a bispecific antibody targeting EGFR and MET tyrosine kinase receptors with immune cell-directing activity. The phase 3 PAPILLON study (NCT04538664) investigated the combination of Ami and carboplatin/pemetrexed (ACP) vs. carboplatin/pemetrexed (CP) as first-line treatment in patients (pts) with advanced EGFR Exon20ins-mutated NSCLC. ACP improved progression free survival (PFS) in both the overall population and Asian subgroup. Methods: Pts were randomized 1:1 to ACP or CP. The primary endpoint was PFS by blinded independent central review (BICR) and key secondary endpoints included objective response rate (ORR), PFS after first subsequent therapy (PFS2), overall survival (OS), and safety. Crossover to Ami monotherapy was allowed for pts in CP arm following disease progression. Results: Among the 308 pts enrolled, 87 were Chinese, with 39 receiving ACP and 48 receiving CP. Median age was 57/57 years, 46%/63% were female, and 15%/25% history of brain metastases for pts in ACP/CP arms. Baseline characteristics were generally balanced between arms. After a median follow-up of 16.4 months (mo), median PFS was 12.3 mo (95% CI: 7.00, NE) in ACP arm compared with 6.7 mo (95% CI: 4.21, 8.57) in CP arm (hazard ratio [HR], 0.47; 95% CI, 0.26-0.85; P = 0.011) (Table). ORR was 71.8% (95% CI, 55.1%-85.0%) for ACP, and 48.9% (95% CI, 34.1%–63.9%) for CP (odds ratio, 2.46; 95% CI, 1.01-5.98; P = 0.048). Median PFS2 was not estimable (NE) for ACP vs 18.8 mo for CP (HR, 0.32; 95% CI, 0.11-0.88; P = 0.021). Interim OS showed a favorable trend for ACP vs CP (HR, 0.58; 95% CI: 0.17-2.02; P = 0.387) despite crossover among CP-randomized pts (n = 24, 50%) who had progressed. Most common AEs (all grades) ( > 50%) in ACP arm were rash, paronychia, hypoalbuminemia, neutropenia, anemia, leukopenia and thrombocytopenia which were consistent with the known safety profile of the individual agents. Notably, no pts had discontinuation of Ami due to an AE. Conclusions: ACP demonstrated superior PFS compared to CP in Chinese pts. The safety profile was manageable and tolerable. These findings in Chinese subgroup were consistent with those of overall population and Asian subgroup. Clinical trial information: NCT04538664 . [Table: see text]
Correlation of the combination of CT-derived tumor texture and vessel tortuosity on survival outcomes for immunotherapy but not for chemotherapy in metastatic non-small cell lung cancer (mNSCLC): Results from a CheckMate227 (CM227) subset.
Authors: Mutha Pushkar , Khorrami Mohammadhadi , Sonuga Babajide , Aggarwal Kshitij , Safta Wiem , Grootendorst Diederik J. , Paulucci David , Mustatea Oana , Nepon Sixt Brook , Witt David , Al-Shakhshir Hilmi , Viswanathan Vidya Sankar , Callahan Jeremy , Velcheti Vamsidhar , Madabhushi Anant 
Published: June 2024

8610 Background: CM227 (NCT02477826) is a large multi-center phase 3 trial that evaluated the benefit of immunotherapy (IO) over chemotherapy (Ch) as first line therapy in stage IV NSCLC. While PD-L1 and tumor mutational burden (TMB) initially emerged as promising biomarkers, CM227 showed benefit of IO over Ch regardless of PD-L1 or TMB status. There is an unmet clinical need for predictive biomarkers to identify patients (pts) who will respond to IO. In this study, we report initial blinded validation results of a CT-derived biomarker combining change in textural radiomics (Δ-Rad) and quantitative vessel tortuosity (Δ-QVT) between baseline and 6-week post-treatment for predicting response and survival outcome of IO and Ch alone in a subset of patients enrolled in CM227. Methods: This retrospective study included baseline (B) and 6-week post-treatment (TP1) CT scans from (a) a multi-center training set (Dtr, N=110) of first line IO-treated mNSCLC pts and (b) a validation set consisting of a subset of mNSCLC from CM227 (Dv, N=224), of which 178 pts were treated with IO (DvIO) and 36 pts (DvCh) with Ch. Intra-tumoral, peri-tumoral texture radiomic (Khorrami et al., Cancer Immunol Res 2020) and QVT (Alilou et al., Sci Adv 2022) features were extracted from up to the two largest measurable lung lesions on each CT using an in-house MATLAB pipeline. Δ-Rad and Δ-QVT features were computed as the feature difference between B and TP1. A best objective IO response classifier, MCombo was trained on Dtr using a combination of Δ-Rad and Δ-QVT features. Kaplan-Meier analyses with log rank p-values, hazard ratio (HR) and its confidence interval (CI) were computed to assess the predictive benefit of MCombo with overall survival (OS) and progression free survival (PFS) in Dv, DvIO and DvCh. We also report area under the receiver operating characteristic (AUC) of IO response predictions compared against best overall response in Dv, DvIO and DvCh. Results: MCombo predicted best overall response with an AUC of 0.67, 0.68, 0.74 in Dv, DvIO, and DvCh, respectively. MCombo was statistically significantly associated with OS and PFS in Dv and DvIO but not in DvCh (Table). Conclusions: Our preliminary findings reveal that combination of CT-based textural and vessel tortuosity features are predictive of IO response over chemotherapy in a subset of CM227 pts. Validation on the entire CM277 cohort is warranted. [Table: see text]
Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) as first-line (1L) therapy for advanced non-small cell lung cancer (aNSCLC): Subgroup analysis from TROPION-Lung02.
Authors: Levy Benjamin Philip , Paz-Ares Luis G. , Su Wu-Chou , Herbert Scott M. , Yang Tsung-Ying , Tolcher Anthony W. , Lou Yanyan , Zenke Yoshitaka , Cortinovis Diego Luigi , Felip Enriqueta , Domine Manuel , Leventakos Konstantinos , Calvo Emiliano , Horiike Atsushi , Pan Edward , Lin Daisy , Jia Xiaoyu , Basak Priyanka , Chisamore Michael Jon , Goto Yasushi 
Published: June 2024

8617 Background: Dato-DXd is an antibody-drug conjugate (ADC) composed of an anti-TROP2 monoclonal antibody linked to a potent topoisomerase I inhibitor payload. We report updated findings from TROPION-Lung02 (NCT04526691) evaluating Dato-DXd plus pembro with or without Pt-CT as 1L therapy for aNSCLC. Methods: Patients (Pts) received Dato-DXd (4 or 6 mg/kg) plus pembro 200 mg alone (doublet) or with Pt-CT (triplet; cisplatin 75 mg/m2 or carboplatin AUC 5) Q3W across 6 cohorts. Pts in the expansion stage were primarily treatment (tx)-naïve. PD-L1 expression was evaluated by tumor proportion score (TPS < 50% or ≥50%) using immunohistochemistry (22C3 assay). The primary objectives were safety and tolerability, with efficacy a secondary objective. Results: 96 pts were treated with doublet (n = 42) or triplet (n = 54) therapy in the 1L setting. At data cutoff (Oct 31, 2023), 45% and 20% of pts receiving doublet or triplet tx were ongoing. Median age was 66 years in both subgroups. Median treatment durations were 6.6 and 5.8 months. Across doublet and triplet tx, the most common any-grade (Gr) treatment-emergent adverse events (TEAEs) were stomatitis (57%, 33%) and nausea (40%, 46%), mainly Gr 1–2. Gr ≥3 TEAEs were seen in 57% and 76% of pts; serious TEAEs in 38% and 44%. TEAEs associated with Dato-DXd discontinuation occurred in 29% and 39% of pts receiving doublet or triplet tx. TEAEs associated with death were seen in 2% and 9%, none considered related to study drug. Efficacy outcomes, including ORR and preliminary PFS, in the 1L setting overall and by PD-L1 status are summarized in the Table. Conclusions: As 1L therapy for aNSCLC, Dato-DXd plus pembro with or without Pt-CT continues to demonstrate durable antitumor activity. Efficacy was observed regardless of PD-L1 expression. Tolerability of the combinations was as expected based on known profiles of the individual agents, with no new safety signals observed. To date, this is the largest dataset reported for any ADC combined with an anti-PD-1/L1 agent in the 1L setting for aNSCLC. Clinical trial information: NCT04526691 . [Table: see text]
Therapeutic activity of a new KRASG12C inhibitor JMKX001899 in brain metastases: Preclinical models of KRASG12C-mutant non-small cell lung cancer.
Authors: He Danming , Wang Jie , Zhu Yixiang , Zhong Jia , Bai Hua 
Published: June 2024

8630 Background: Development of therapies targeting KRAS have transformed KRAS from undruggable to druggable. However, patients with KRASG12C-mutant non-small cell lung cancer (NSCLC) with brain metastasis (BM) have a poor prognosis. JMKX001899, a new potent oral small-molecule KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state. Its antitumor activity in the intracranial is unclear. Methods: In order to verify the activity of new KRASG12C inhibitor JMKX001899 in KRASG12C-mutant NSCLC with BM, murine models were employed for investigating the efficacy. 5-6 weeks old female Balb/c nude mice were implanted intracranially with H358-Luc and H23-Luc cells. Baseline bioluminescent imaging (BLI) was used to monitor the tumor burden and total flux was calculated by Living Image. Ten days after implantation, oral once-daily dosing of vehicle, sotorasib (AMG510) at 100 mg/kg, 30 mg/kg and JMKX001899 at 100 mg/kg, 30 mg/kg, 10 mg/kg was started and continued for 21 days. The tumor burden was monitored by BLI weekly. The mice were weighed per 3 days. Results: At the 30mg/kg and 100mg/kg dose level, the mean cerebrospinal fluid (CSF)-to-unbound plasma ratios (Kp,uu) was 0.18-0.50, which determined JMKX001899 CSF exposure was sufficient to mediate regression tumors in experimental BM models. In mice bearing intracranial xenografts of H358-Luc and H23-Luc, oral JMKX001899 100mg/kg once daily treatment for 21 days resulted in significant inhibition of brain tumor growth revealed by BLI, compared with vehicle and AMG510. H358-Luc xenografts responded particularly well to the JMKX001899 treatment, showed by the ratio of 14 days and 0 days total bioluminescence flux (vehicle vs. AMG510 100mg/kg vs. JMKX001899 100mg/kg, 0.85 vs. 0.89 vs. 0.01, p < 0.05). In addition, JMKX001899 at 100mg/kg once daily demonstrated an increase in over survival. JMKX001899 100 mg/kg once daily treatment was well tolerated with minimal sign of overt toxicity or animal weight loss. Conclusions: The preclinical models in vivo suggest the new KRASG12C inhibitor JMKX001899 penetrates the central nervous system and show great inhibition of KRASG12C-mutant NSCLC with BM, which demonstrates therapeutic activity of JMKX001899 in BM. These data support further development of JMKX001899 in patients with KRASG12C-mutant NSCLC with BM.
International medical graduates (IMG) representation at international oncology conference meetings.
Authors: Roy Arya Mariam , Bakouny Ziad , Dizman Nazli , Ozay Zeynep Irem , Mohan Lal Bhavesh , Nawfal Rashad , Eid Marc , El Hajj Chehade Razane , Machaalani Marc , Butt Ayesha , Aggarwal Charu , Bekaii-Saab Tanios S. , Chavez-MacGregor Mariana , Lopes Gilberto , Marshall Ariela Lucy , Murphy Martina Cathryn , Owonikoko Taofeek K. , Lee Alfred Ian , CHOUEIRI Toni K. 
Published: June 2024

9000 Background: Despite IMGs accounting for up to one-third of all practicing oncologists in the United States, little is known about their contributions to presentations at international oncology meetings, such as the American Society of Clinical Oncology (ASCO). Therefore, we investigated the representation of IMGs in invited faculty roles at ASCO Annual Meetings. Methods: Speaker presentation details at ASCO 2022 and 2023 Annual Meetings were collected using publicly available program guides. We collected presentation-level variables of invited faculty roles (discussant, moderator, chairmanship, session topic presenter) and original research type (oral abstract, poster discussion, plenary session). Speaker-level variables comprised presumed gender, academic rank, and institution. Speakers were categorized into the following groups - American Medical Graduate (AMG): currently affiliated with a US institution, completed medical school in the US; IMG: affiliated with a US institution, completed medical school outside the US; non-US based speakers: affiliated with an institution outside the US; non-MD speakers. Univariable and multivariable analyses were employed to assess factors associated with the selection of presenters for invited faculty roles. Results: A total of 3337 presentations (1649 from 2022, 1688 from 2023) were included. 71.6% of the speakers were US-based, 56.6% were male and 40.5% were full professors. The highest proportion of podium presentations was by AMGs (48.5%), followed by non-US based (28.3%), IMGs (14.1%), and non-MD (9.1%) speakers. 57% of IMG presentations consisted of original research compared to 48.7% for AMGs (Table). Notably, compared to AMGs, IMGs were significantly less likely to be included in invited faculty roles (odds ratio [OR] 0.72 [95% CI 0.58 – 0.88], p <0.01), a finding that remained significant after accounting for gender and academic rank (adjusted OR 0.75 [0.61 – 0.94], p= 0.01). Conclusions: Relative to IMGs’ original research output, IMGs appear to receive less invitations for ASCO Annual Meeting invited faculty roles compared to AMGs. Our findings suggest potential under-representation and under-recognition of IMGs in these roles, despite their contributions to the oncology workforce in the US. [Table: see text]
Evaluating speaker gender in scientific sessions at ASCO and ASCO GI (2019-2023).
Authors: Shroff Rachna T. , Morris Van K. , Lin Kangyu , Kunz Pamela L. 
Published: June 2024

9009 Background: Gender disparities exist in medicine, including academic and medical society leadership, journal editorial boards, and research teams. Women are also underrepresented in clinical trial leadership and authorship, with one study reporting fewer than 10% female corresponding authors for randomized clinical trials in GI Oncology, GU oncology, and Hematology. Clinical trial leadership, subsequent podium presentations and authorship have downstream effects on promotion, reputation, and funding opportunities. We examined the gender of speakers in scientific sessions at the ASCO Annual Meeting (AM) and Gastrointestinal Symposium (ASCO GI) from 2019-2023. Methods: We examined speaker gender, role (session chair, abstract presenter, abstract discussant), speaker region (Asia, Europe, N. America), and presentation topic (colorectal cancer or non-colorectal cancer) for the ASCO AM GI scientific sessions and ASCO GI from 2019-2023. For the ASCO AM, we included GI oral abstracts and plenary sessions; for ASCO GI we included oral and rapid abstracts. Self-identified gender was not available; therefore, gender was assigned by physical appearance via ASCO video or institutional websites. Statistical analyses were performed using the two-proportions z-test with a p value <0.05 considered statistically significant. Results: 208 scientific abstracts were reviewed across both meetings over 5 years. There was a statistically significant difference in the % of men vs. women as abstract presenters (77% vs 23%, p <0.001). This did not differ when looking at ASCO and ASCO GI separately (ASCO 76% vs 24%, ASCO GI 78% vs 22%, p <0.001 for both) and was observed across all 5 years. Similarly, there was a predominance of men as abstract presenters regardless of speaker region (Asia 93%, Europe 74%, N. America 67%, p<0.001 for all) and presentation topic (CRC 76% vs 24%, non-CRC 78% vs. 22%; p <0.001 for both). The percent of men as repeat presenters for scientific abstracts was statistically higher than women (84% vs 16%, p <0.001). Importantly, there was no difference in men vs. women in the invited chair/discussant roles (51% vs 49%, p = 0.89). Conclusions: Our analysis of 5 years of scientific sessions for ASCO and ASCO GI shows a stark difference in the proportion of men vs women as abstract presenters regardless of presentation topic, region of presenter, and meeting year. Our data highlight the need for all trial sponsors to be more intentional in the selection of principal investigators and lead authors as these opportunities are critical to the promotion of women in GI Oncology and to diversifying approaches to clinical trial design and access. Our data is limited by how gender was assigned (i.e., not self-reported). Lastly, we commend ASCO on their efforts to ensure gender equity among the roles that are within their control, and we advocate for them to consider opportunities for self-identification of gender in their membership directory.
Utilizing data to drive solutions for healthcare worker wellbeing.
Authors: Gallagher Amy , Faller Julia , Cianchetti Kristin , Nurkin Steven J. , Mann Gary , Case Amy Allen 
Published: June 2024

9012 Background: Oncology Healthcare Workers (HCWs) provide extraordinary treatment to patients coping with distinct challenges. While experiences of burnout, compassion fatigue, and moral distress are not new, the COVID-19 pandemic further emphasized that intentional effort is needed to mitigate these negative work-related consequences. While Roswell Park Comprehensive Cancer Center (Roswell) initiated pre-pandemic grassroots efforts to examine burnout and build organizational resilience, deliberate resources were deemed necessary to support HCW resilience and well-being. Roswell committed to building a division solely focused on employee resiliency and burnout prevention. Methods: Qualitative and quantitative data were collected to identify organizational needs and pain points. Qualitative data was collected by the Resiliency Director who held over 100 conversations in 100 days with diverse personnel across the institute. Discussions focused on two questions (e.g., What’s working well? and What are the pebbles in employees’ shoes?) to assess organizational strengths are growth areas. Quantitative data was obtained through the Mini-Z, a validated burnout screener. All employees were emailed an invitation to take the survey over an 8-week period starting in December 2022. Concerned employees could self-refer to the Employee Assistance Program at the screener’s conclusion. Results: Qualitative data was categorized into Maslach's burnout drivers (workload, relationships, recognition, fairness, autonomy, and values conflict). Highlights included staff shortages, eroding of relationships during the pandemic, siloed communication, inconsistent recognition, micromanagement, and use of antiquated systems. Mini-Z results are displayed in the table. An interactive dashboard helped further examine demographics, role, and departmental data. Press Ganey employee engagement data also supported improvements for staff well-being, transparent communication, collaboration, recognition, and enhanced technology. Conclusions: Quantitative and qualitative data can drive individual, departmental, and organizational interventions to support HCW well-being. The newly established MedStaff Satisfaction and Wellness group is using the data to focus on recognizing the needs of the medical staff on an organizational level and is preparing to offer solutions to key stakeholders. HCWs are now incorporating activities aiming to build psychological safety, enhance communication, and advance well-being into their work routines through training, wellness activities, and emotional support. The Mini-Z screener has been made available in the Employee Health Portal permitting ease of personal reassessment. [Table: see text]
Observing attending physician teaching behaviors during inpatient hematology/oncology consultation.
Authors: Trainer Michael , O'Sullivan Patricia , Brondfield Sam 
Published: June 2024

9017 Background: Inpatient consultation is a primary responsibility of fellows and residents. Consults are complex tasks that impose significant cognitive load (CL) on trainees, potentially jeopardizing patient safety. We previously published strategies for attendings to optimize trainee CL during consults, and we also demonstrated that distractions are a prominent source of trainee CL during consults. Strategies to optimize CL have not been studied during inpatient consultation. Therefore, we aimed to observe and categorize attending behaviors that might affect trainee CL during consults using hematology/oncology as a model. Methods: After discussion with author SB (an oncologist who frequently performs and teaches inpatient oncology consultation), one author (MT, a neurology resident with experience performing consults outside of hematology/oncology) observed 10 new inpatient hematology and oncology consult discussions between attendings and fellows or residents at the University of California, San Francisco in 2023. The observer used our published set of strategies, divided into the three CL types (intrinsic load [IL] strategies to optimize the consult for the trainee, extraneous load [EL] strategies to reduce distractions, and germane load [GL] strategies to promote learning), as a checklist of attending behaviors and noted whether each behavior occurred during the discussions. Results: Discussions between four attendings and five trainees (three fellows and two residents) on inpatient hematology and oncology consult services were observed. Two attendings identified as female (one hematologist and one oncologist) and two male (one hematologist and one oncologist). Out of 18 attending behaviors on the checklist (six each of IL, EL, and GL), 13 (72%) were observed at least once. The median number of behaviors observed during one consult discussion was 3.5 (range 1-5, interquartile range 2-4.75). GL behaviors occurred most often (14 times across the 10 discussions), IL behaviors next most often (11 times), and EL behaviors least often (seven times). All four attendings exhibited at least one behavior from each CL type. The most commonly observed behavior was “teaching by sharing clinical reasoning” (GL). Conclusions: Hematology/oncology attendings exhibited observable behaviors related to optimizing trainee CL during inpatient consults and demonstrated behaviors intended to promote learning (GL) more frequently than behaviors intended to reduce trainee distractions (EL). Based on these data, hematology/oncology consult attendings may wish to augment their use of behaviors intended to reduce distractions, which are prominent during inpatient consults, to avoid trainee cognitive overload. Future research might correlate measured trainee CL with attending teaching behaviors to demonstrate the impact of these behaviors and optimize consult teaching interactions.