tbuckley/cabot-search huggingface dataset:
Surveying oncologists' awareness and challenges in addressing social determinants of health: A national study.
Authors: Heather Drew, Michael Beyer, Chris Kriz, Tomas Colas, Stephany Vargas, Ted Singer
Journal: Journal of Clinical Oncology (2024)

9030 Background: Ensuring that healthcare professionals are equipped to address disparities in healthcare access and outcomes is crucial for improving overall healthcare quality. Multiple studies have shown a clear causal link between social determinants of health (SDOH) and cancer. PeerView developed a research project to understand how well oncologists understand the impact of SDOH on the care and outcomes of patients with cancer and what they need to close gaps in knowledge and skills in order to deliver equitable care. Methods: PeerView developed and sent a series of seven surveys, each with 3-5 questions, to US medical oncologists and hematologist-oncologists from June 2023 to January 2024. Each set of surveys was sent to a different group of clinicians to ensure that responses were representative of the target group. Key Areas of Analysis: Overall awareness and understanding of SDOH; Perceived challenges in achieving health equity; Barriers to improving diversity in clinical trials; Clinician needs in addressing disparities; and Educational tactics and tool preferences for SDOH training. Results: 1,536 responses from US medical oncologists and hematologist-oncologists (37% working in an academic setting; 63% community-based) Representative findings: Approximately two-thirds (67%) needed to improve their understanding of SDOH and their effects on healthcare disparities; 60% were confident in their understanding of the effects of SDOH in cancer care in 4 key areas: care delivery and quality, screening, immunotherapy efficacy, and technology literacy; Most respondents felt confident or very confident caring for patients with cancer across ethnicities (81%), cultures (83%), socioeconomic statuses (78%), genders/gender identities (82%), and age (89%); 70% expressed confidence in their ability to identify patients at higher risk because of health disparities and SDOH; While the majority (61%) felt competent in connecting patients with resources and care to overcome SDOH-related barriers, community and academic providers differed significantly in their confidence; 70% selected the lack of resources in the healthcare system as the most or second greatest significant factor contributing to healthcare disparities; and 58%believed that partnering with pharmacists, community health workers, and community groups would help increase minority participation in oncology clinical trials. Conclusions: These results outlined deficiencies in knowledge and confidence of SDOH. By integrating these insights into development of continuing education (CE) activities and sharing them with the CE community, we can help clinicians overcome care-delivery barriers related to SDOH and develop inclusive care practices that empower patients to take charge of their health. Furthermore, insights from this research can shape policy decisions, curriculum development, and resource allocation on a larger scale.
Assessing gender disparities in oncology: Less talk, more action.
Authors: Coral Olazagasti, Claudia Villa Celi, Ana I. Velazquez Manana, Arthi Sridhar, Miki Horiguchi, Arun Mahtani, Nazli Dizman, Mariana Gonzalez Nororis, Carolina Bernabe, Narjust Florez
Journal: Journal of Clinical Oncology (2024)

9011 Background: 'Gender disparities' is a familiar term in medicine. Only 35.2% of oncologists in the U.S. self-identified as women in 2021. Women in medicine are undercompensated and underpromoted. Little is known of the experiences of non-U.S. female physicians in the U.S. We created the first cross-sectional study to assess gender disparities in IMGs and Puerto Rican medical graduates (PRMGs) in oncology in the U.S. Methods: An anonymous online survey was created and distributed via Survey Monkey. Eligible participants were non-U.S. IMGs and PRMGs who trained and/or practiced independently in the U.S. Participants were recruited through email and social media from Sept-Dec 2023. Bivariate association analyses were performed using the two-sample Wilcoxon test for ordered categorical variables and Fisher’s exact test for nominal categorical variables. Results: 97 IMGs and PRMGs in oncology completed the survey. As shown in the table, women were more likely to move to the U.S. for family (22.4% vs 6.2%, p=0.040), whereas men did more for financial gains (20.8% vs 6.1%, p=0.040). culture, particularly to the traditions (65.3% vs 43.8%;p=0.042) and dress code (44.9% vs 20.8%, p=0.017). Women experienced higher rates of gender discrimination during training (53.2% vs 4.5%, p &lt;0.001) and independent practice (57.6% vs 3.6%, p&lt;0.001) than men. Women were also more likely than men to face ethnic/racial discrimination during training (69.6% vs 38.1%; p=0.005). Despite lack of statistical significance, higher trends of ethnic/racial discrimination during independent practice were reported by women (table). More women reported no plans on returning home (68.8% vs 38.3%), whereas more men planned to return home at some point (38.3% vs 16.7%). 18.8% of men vs 0% of women elected leadership opportunities as the reason for returning to their home country (p=0.001). Conclusions: Our study reveals the unfortunate reality that many IMG and PRMG women face in oncology in the U.S. Despite national efforts to reduce the gap in gender disparities, minority women continue to experience racial/ethnic and gender discrimination at higher rates than men. To overcome inequities and achieve gender equity pay transparency, diversity in selection committees is necessary. Further, efforts should be across all settings, academia, private practice, and industry. The time for gender equity in oncology is now. [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: Benjamin Philip Levy, Luis G. Paz-Ares, Wu-Chou Su, Scott M. Herbert, Tsung-Ying Yang, Anthony W. Tolcher, Yanyan Lou, Yoshitaka Zenke, Diego Luigi Cortinovis, Enriqueta Felip, Manuel Domine, Konstantinos Leventakos, Emiliano Calvo, Atsushi Horiike, Edward Pan, Daisy Lin, Xiaoyu Jia, Priyanka Basak, Michael Jon Chisamore, Yasushi Goto
Journal: Journal of Clinical Oncology (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/m 2 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 &lt; 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]
Multidimensional analysis of B7 homolog 3 (B7-H3) RNA expression in small-cell lung cancer (SCLC) molecular subtypes.
Authors: Carl Michael Gay, Taofeek K. Owonikoko, Lauren Averett Byers, Noura J. Choudhury, Sajid Ahmed, Zachary Cain, Xiaozhong Qian, Matthew Brentnall, Simon Heeke, Ming Poi, Sharon Wu, Charles M. Rudin
Journal: Journal of Clinical Oncology (2024)

8088 Background: SCLC is an aggressive cancer with a poor prognosis. B7-H3, a transmembrane protein showing low expression in normal tissues but overexpression in SCLC and other tumors, is a promising target for antibody–drug conjugates. We performed a multidimensional analysis of B7-H3/ CD276 expression in SCLC molecular subtypes (SCLC-A, -N, -P, and -I) and its relationship with expression of other immune-related genes. Methods: Clinical and molecular data for a cohort of patients (pts) with SCLC were derived from a real-world database (Caris Life Sciences, Irving, TX, USA). Tumor RNA expression was used to assign the SCLC molecular subtype derived from non-negative matrix factorization. Programmed death ligand-1 (PD-L1) protein expression was assessed by immunohistochemistry (IHC; antibody 22c3; positive cut-off: tumor proportion score &gt;1%). Demographic, clinical, and molecular data were summarized by SCLC subtype or B7-H3 expression quartile (Q). Spearman’s r evaluated correlations between expression of B7-H3 and other immune-related genes/signatures. Results: The cohort included 1721 pts (52.5% female; 98.9% [434/439] smokers; median age, 67 years [range, 18–90+]). Across the subtypes, B7-H3 expression was high and remarkably consistent ( q&gt;0.05; Table). Other biomarker genes, including DLL3 (q&lt;0.05), had lower and more variable expression. Median (range) B7-H3 expression across all samples was 16.75 (0–68.2) transcripts per million (TPM). Across B7-H3 expression Qs, the proportion of PD-L1-positive pts by IHC was similar (Q1, 39.8%; Q2, 46.5%; Q3, 40.7%; Q4, 39.2%). Median (95% confidence interval) B7-H3 expression was similar between pts with prior immunotherapy ( n=24; 14.43 [11.64–21.17] TPM) and pts without ( n=208; 14.20 [13.00–15.91] TPM); treatment information was not available for the remaining samples in this cohort. B7-H3 expression was not strongly correlated with any other immune-related genes/signatures, although several had moderate correlation ( HAVCR2/ TIM3, r=0.59; PDCD1LG2/ PD-L2, r=0.56; M2 macrophages, r=0.56; CD86, r=0.56). Conclusions: In pts with SCLC, B7-H3 showed high and consistent expression across subgroups defined by molecular subtype or prior immunotherapy. The relative expression of B7-H3 was higher and less variable among molecular subtypes than for other key molecular targets in this tumor type, including DLL3. B7-H3 expression had limited association with PD-L1 expression, supporting a role as a distinct therapeutic target. [Table: see text]
Final analysis of SCARLET study: A single-arm, phase II study of sotorasib plus carboplatin-pemetrexed in patients with advanced non-squamous, non-small cell lung cancer KRAS G12C mutation.
Authors: Hiroshige Yoshioka, Hiroaki Akamatsu, Shinya Sakata, Koichi Azuma, Takehiro Uemura, Yuko Tsuchiya-Kawano, Mitsuo Osuga, Yasuhiro Koh, Satoshi Morita, Nobuyuki Yamamoto
Journal: Journal of Clinical Oncology (2024)

8616 Background: Efficacy and safety of sotorasib in combination with platinum-doublet chemotherapy in KRAS G12C-mutated non-squamous, non-small cell lung cancer (non-Sq, NSCLC) has been reported with a limited follow-up period. Methods: Efficacy and safety of sotorasib in combination with platinum-doublet chemotherapy in KRAS G12C-mutated non-squamous, non-small cell lung cancer (non-Sq, NSCLC) has been reported with a limited follow-up period. Results: Between Oct 2021 and Jul 2022, 30 patients were enrolled and the median follow-up time was 14.8 months (range, 0.6-21.7). The primary endpoint, ORR by independent review was 88.9% (80%CI 78.5-94.8%, 95%CI 70.8-97.6%). Median PFS was 6.6 months (95%CI 5.3-16.7 months) and PFS rate at 12 months was 37.0%. Median time to treatment failure was 7.9 months (95%CI 5.4-13.9 months). Median OS was 20.6 months (95%CI 8.1 moths - not estimated) and OS rate at 12 months was 66.7%. Similar to the initial report, efficacy did not differ by PD-L1 expression level. In patients with PD-L1 expression level ≥50% / 1-49% / &lt; 1%, ORR was 76.9% / 100.0% / 100.0%, and median PFS was 7.6 / 5.7 / 9.7 months, respectively. Common adverse events were anemia, platelet count decreased, neutrophil count decreased, decreased appetite and nausea. Grade≥3 AEs were mostly hematological toxicities, and one treatment-related death (pneumonia) occurred. Twenty-two plasma samples were collected and analyzed using NGS at the time of disease progression. Of those, an increased allele frequency of KRAS G12C was observed in 73% of the patients. TP53 mutation was detected in 55%, and other resistance mechanisms included CDKN2A, BRAF and PIK3CA mutations. Conclusions: Sotorasib in combination with CBDCA/PEM demonstrated favorable ORR with modest PFS and good tolerability in advanced non-Sq, NSCLC patients with KRAS G12C mutation. Clinical trial information: jRCT2051210086 .
Alignment of patient-clinician perspectives in triple-negative breast cancer (TNBC).
Authors: Tariqa Ackbarali, Chelsey Goins, Stephanie Walker, Sara Donahue, Jennifer Witt, Gregory A. Vidal, Tiffany A. Traina
Journal: Journal of Clinical Oncology (2024)

9032 Background: Despite recent advances in therapeutic strategies, TNBC remains difficult to treat due to a poor prognosis and a reduced number of effective treatments. Among racial and ethnic groups, Black and Hispanic women have a disproportionately higher risk of TNBC. To address this, a tethered educational initiative was designed to empower patients through navigation and treatment decision-making, and facilitate patient-clinician partnerships through education and the sharing of real-world outcomes. Methods: Two, one-hour online, interactive, video-based programs were designed for patients/caregivers, and clinicians in collaboration with TOUCH, the Black Breast Cancer Alliance and the National Breast Cancer Foundation. The patient/caregiver program was hosted on CancerCoachLive and MedLive and the provider program hosted on OMedLive; both launching in June 2023. Patient stories were embedded within the program. We report on an analysis of patient outcomes and the intersection of patient and clinician perspectives, including behavioral impact, and qualitative insights. Results: To date, more than 2,000 participants have engaged across both educational programs. Of participating patients/caregivers, 42% were non-White (non-Hispanic) and 76% were people diagnosed with breast cancer. Following the program, 82% felt confident discussing treatment and outcomes with their healthcare team, and 56% reported intent-to-change related to treatment, communication, and engagement with support resources. Patient/caregiver participants (56%) defined ‘providing resources and information about diagnosis and treatment options’as the most helpful role in working with a patient navigator. Qualitative data elucidating specific intended changes and patient experiences will be shared. Of the participants in the clinician program, 89% were physicians, 91% of whom noted their specialty as oncology. In assessing patient openness to discussions with their team; 42% of clinicians believed their patients would approach them, and 71% of patients were very likely to approach their team. Only 60% of clinicians believed their patients would participate in a clinical trial while 85% of patients reported they would be likely to participate. Clinicians reported challenges enrolling patients in clinical trials as: lack of access (33%), low awareness of available trials (17%), and patient lack of interest (15%). Conclusions: Discordances in patient and clinician perspectives were revealed by the outcomes related to willingness of patients to engage in clinical trials and openness in communication between patients and their healthcare teams. These educational programs positively impacted patient and clinician motivation to address areas of care within their control. Real-world accounts of patient experiences provided context and perspectives that can help improve shared decision-making approaches.
KRAS mutation subtypes responded differently to combination immunotherapy via disturbing myeloid-derived suppressor cells in non-small cell lung cancer.
Authors: Caifeng Gong, Xu Yang, Jinsong Zhang, Rui Wan, Jia Zhong, Zhijie Wang, Jie Wang
Journal: Journal of Clinical Oncology (2024)

8635 Background: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy has shown high efficacy in non-small cell lung cancer (NSCLC) patients, but further exploration of the predictive biomarkers is needed. KRAS is the most common driver oncogene in patients with NSCLC. However, the influence of different KRAS mutation subtypes on immunotherapy response remains controversial. We aimed to evaluate the value of KRAS mutation subtypes for predicting response to immunotherapy in NSCLC patients and to further analyze the related tumor immune microenvironment (TiME) phenotypes. Methods: In this retrospective study, clinical data were extracted from the medical records of patients with advanced NSCLC treated with ICIs and whose available molecular analysis included KRAS mutation information between January 2017 and December 2022. NSCLC tissue samples were collected for TiME analysis. Differences in immune cell subsets between different groups were analyzed using the Mann‒Whitney U test. Clinical characteristics, ICI treatment efficacy, progression-free survival (PFS), and overall survival (OS) were analyzed using multivariate Cox models. Results: A total of 1913 eligible KRAS-mutated NSCLC patients were screened, and 137 patients who received systemic immunotherapy were enrolled (108 males vs 29 females), with a median age of 62 (range, 39-84) years. Among them, 126 (92.0%) patients had adenocarcinoma, 99 (72.3%) patients were systemic therapy naïve, and 124 (90.5%) patients received combined immunotherapy. Among the patients with KRAS mutations, 48 (35.0%) had G12C, 20 (14.6%) had G12V, 27 (19.7%) had G12D and 42 (30.7%) had other subtypes. PFS was significantly longer in the G12C subgroup than in the other mutation subgroup (median PFS: 11.3 vs 6.8 months, P = 0.001). The median PFS times in the G12C/G12V subgroup and the other groups were 11.1 months and 6.5 months, respectively ( P= 0.0005). Multivariate analysis of the immunotherapy cohort revealed that G12C/G12V was an independent predictor of PFS ( P = 0.003, hazard ratio (HR): 2.021, 95% CI: 1.265-3.227). Further TiME analysis suggested that the infiltration of myeloid-derived suppressor cells (MDSCs, CD33+CD11b+) in the tumor and stromal areas in the G12C/G12V subgroup was significantly lower than that in the other subgroup (tumor area, P= 0.045; stroma area, P= 0.015). However, no significant difference in PD-L1 expression was found between the G12C/G12V group and the other groups. Conclusions: KRAS G12C and G12V were associated with favorable combined ICI treatment efficacy in patients with NSCLC. Patients with G12C or G12V mutations had longer PFS and lower infiltration of MDSCs. KRAS mutation subtypes are potential predictive biomarkers disturbed by MDSCs for combination therapy in NSCLC patients.
FDA analysis of immune checkpoint inhibitors in combination with vascular endothelial growth factor tyrosine kinase inhibitors in the second-line treatment of patients with advanced non-small cell lung cancer.
Authors: Justin Nathaniel Malinou, Gautam Mehta, Paz J. Vellanki, Erin A. Larkins, Paul Gustav Kluetz, Harpreet Singh
Journal: Journal of Clinical Oncology (2024)

8595 Background: Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 in combination with platinum-based chemotherapy is standard first-line therapy for patients with advanced non-small cell lung cancer (NSCLC). The majority of these patients progress and there remains a high unmet medical need in the second-line setting given the limited FDA approved available therapies. The ICI plus vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) combination, successful across several tumor types, was studied in NSCLC as a potential treatment option. Methods: The FDA identified 3 randomized trials conducted between June 2019 and August 2023, comparing the combination regimen ICI plus VEGF TKI to docetaxel in patients with advanced NSCLC who had progressed on both platinum-based chemotherapy and an ICI. All 3 trials were publicly reported to have not met their primary endpoint. Topline results for key efficacy and safety outcomes from each of the 3 trials were provided by the commercial sponsors. Results: 1317 total patients across 3 trials (LEAP-008, SAPPHIRE and CONTACT-01) were randomized to receive either an ICI plus VEGF TKI or docetaxel. The results are presented (Table). Efficacy parameters demonstrated similar results across trials between arms. There was no clear signal that the combination is more effective than single agent docetaxel. Safety parameters across trials consistently demonstrated higher rates of toxicity with the combination. Conclusions: ICI plus oral VEGF TKI combinations have not demonstrated an advantage over docetaxel in randomized trials of patients with advanced NSCLC. In 2 of the 3 trials, response rate data did not demonstrate superior efficacy compared to docetaxel. Additionally, any observed PFS benefit was small in magnitude. The relatively low efficacy, in combination with the additive toxicity of the regimen, may curtail a potential OS benefit. There remains a high unmet medical need in this patient population and further analysis is necessary to explore potential NSCLC subgroups which may derive benefit. [Table: see text]