Trial Enrollment Research Articles

Measuring Representativeness in Clinical Trials.

Representativeness in randomized clinical trials remains a critical concern, affecting the external validity of trial results, equitable access to the risks and benefits of research participation, and public trust in clinical research. Although representative participation by members of groups traditionally underrepresented in clinical trials is just a surrogate for true diversity, equity, inclusion, and belonging in clinical trials, it can be quantified, allowing stakeholders to add empirical rigor to diversity, equity, inclusion, and belonging efforts. Multiple ways to measure representativeness have been proposed, including the participation-to-prevalence ratio, raw participation proportions or numbers for relevant subgroups, and enrollment fraction for relevant subgroups. These methods have strengths and weaknesses and may be appropriate to report in certain circumstances, depending on why stakeholders seek to assess representativeness. Stakeholders-including regulatory agencies, journal editors, clinical trial investigators, and trial sponsors-may use quantitative measures of representativeness to establish trial enrollment standards, monitor equitable participation in ongoing trials, and condition funding or drug or device approval on achieving specific representativeness targets. However, using quantitative measures of representativeness in this way could have unintended consequences, including researchers "gaming" recruitment strategies to meet target numbers, overlooking nuanced variations within communities, and potentially incentivizing problematic and exploitative recruitment strategies. Although no single method of measuring representativeness offers a comprehensive solution for increasing diversity, equity, inclusion, and belonging in all randomized clinical trials, a carefully designed, multifaceted approach to measuring representativeness may provide stakeholders with useful perspectives for measuring progress in increasing the diversity of clinical trial participation. For stakeholders seeking a single number to assess the representativeness of a trial enrolling patients with a disease state with well-delineated demographics, the participation-to-prevalence ratio is ideal; however, for a more nuanced view of representativeness, the combination of enrollment fraction in subgroups of relevance plus a full report of the demographics of patients approached for enrollment may be more appropriate.

Determinants of first-line clinical trial enrollment among Black and White gynecologic cancer patients.

Disparities in gynecologic cancer clinical trial enrollment exist between Black and White patients; however, few examine racial differences in clinical trial enrollment predictors. We examined whether first-lineclinical trial enrollment determinants differed between Black and White gynecologic cancer patients. We used the National Cancer Database to identify Black and White gynecologic cancer (cervix, ovarian, uterine) patients diagnosed in 2014-2020. Multivariable logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between clinical trial enrollment (yes vs no) and sociodemographic, facility, tumor, and treatment characteristics stratified by race. We included a multiplicative interaction term between each assessed predictor and race to test whether associations differed by race. We included 703,022 gynecologic cancer patients (mean [SD] age at diagnosis, 60.9 [13.1] years). Clinical trial enrollment was lower among Black (49/86,058, 0.06%) vs. White patients (710/616,964, 0.11%). Only cancer site differed by race: among Black patients, a cervical vs. uterine cancer diagnosis (OR = 4.63, 95% CI = 1.67-12.88) was associated with higher clinical trial enrollment odds, while among White patients, both cervical (OR = 2.21, 95% CI = 1.48-3.29) and ovarian (OR = 3.40, 95% CI = 2.58-4.47) cancer diagnoses (vs. uterine cancer) were associated with higher enrollment odds. Most predictors were associated with clinical trial enrollment odds among White but not Black patients. Few differences in first-lineclinical trial enrollment predictors exist between Black and White gynecologic cancer patients. Although small numbers of Black patients and low clinical trial prevalence are limitations, this descriptive analysis is important in understanding racially disparate clinical trial enrollment.

Adequate racial and ethnic representation in cancer clinical trial enrollment: Real-world evidence from an NCI-designated cancer center in a minority-majority county.

803 Background: Despite strides to increase diversity in clinical trial enrollment, significant racial and ethnic disparities persist. This limits the generalizability of clinical trial data and consequently the application of novel therapeutics for diverse populations. We hypothesized that enrollment of underrepresented minorities (URM) is feasible, with improved access to clinical care and a tailored clinical trial portfolio addressing the unmet needs in URM. Methods: A retrospective cohort study was conducted at the University of California Irvine Chao Comprehensive Cancer Center (CFCCC), an NCI-Designated cancer center located in Orange County (OC), CA (a minority-majority county). Clinical trial enrollment data from 2015-2023 through the CFCCC clinical research database was included. Collected data on patient demographics, tumor types, and trial enrollment was compared to data provided by the NIH SEER reports in both OC and United States. Results: Between 2015-2023, 2317 subjects were enrolled in clinical trials at CFCC. Demographics were as follows: White, Asian, Black, American Indian/Alaska Native, mixed/unknown race (66.4%/20.1%/2.4%/0.7%/0.7%/9.3%). Non-Hispanic vs Hispanic ethnicity (77.8%/20.5%). Female vs Male sex (47.6%/52.3%). Age <70 vs >70 years (73.3%/26.7%). Study Phase: Phase I/II (35.6%), Phase II (25.4%), Phase II/III (2.8%), Phase III (26.6%), and Phase IV (0.3%). Study sponsor: Industry (61.1%), Institutional (23.6%), National (14.8%), and Externally Peer Reviewed (0.3%). Most notably, the Asian enrollment (20.1%) and Hispanic enrollment (20.6%) exceeded demographic representation of Asians (17%, RR 1.18) and Hispanics (19%, RR 1.07) at CFCCC. Lastly, Asian patients enrolled at significantly higher rates in lung and liver cancer trials, while Hispanic patients and Black patients enrolled at higher rates in breast cancer and prostate cancer trials respectively. Conclusions: Our results demonstrate that robust URM clinical trial enrollment, particularly among Asian and Hispanic populations, is feasible at an NCI-designated cancer center despite minority-specific barriers. These findings suggest that minority populations can be optimally enrolled in clinical trials when these trials are accessible and tailored to the population at hand. Further research is necessary to investigate factors that influence clinical trial participation in the pursuit of equitable cancer care.

Optimizing clinical trial design to mitigate racial disparities in pancreatic cancer clinical trial enrollment.

682 Background: Participation in pancreatic ductal adenocarcinoma (PDAC) clinical trials remains dismal among patients from minoritized groups. This study aimed to investigate if clinical trial design, including eligibility criteria, affects representation of minoritized populations. Methods: United States Phase I-IV PDAC clinical trials between 2000-2020 were extracted from the ClinicalTrials.gov database. The Surveillance, Epidemiology, and End Results (SEER) database was used to determine cancer incidence linked with years of trial enrollment. Enrollment fraction (EF) was defined as the number of trial participants divided by the incidence of PDAC in each racial and ethnic group. Representation Quotient (RQ) was defined as the proportion of trial participants divided by proportion of PDAC incidence for each subgroup, where underrepresentation was RQ <1.0. Results: 8451 patients from 228 unique PDAC clinical trials were analyzed. 55.7% (n=128) and 44.3% (n=102) trials reported racial and ethnic demographic data, respectively. Non-Hispanic Black (NHB), Non-Hispanic Asian/Pacific Islander (NHAPI), Non-Hispanic American Indian/Alaskan Native (NHAIAN), and Hispanic patients were underrepresented (Table). NHB patients were more likely to be underrepresented in trials for metastatic PDAC disease (89.4% vs. 73.8% of trials, p=0.035). NHB patients demonstrated an increase in median RQ (0.28 vs. 0.48) in trials from 2000-2010 vs. 2011-2020, while Hispanic patients had a decreased median RQ (0.36 vs. 0.25). Trials with renal insufficiency exclusion criteria without cutoffs or explicit methodology were more likely to accrue NHB patients (RQ 0.88 vs. 0.46, p=0.02), whereas trials that used a creatinine cutoff or the modified Cockcroft-Gault (CG) formula did not significantly affect RQ. Other eligibility criteria including cardiac history, HIV, Hepatitis B/C, and receipt of neoadjuvant therapy did not significantly affect RQ for any racial or ethnic group. Trial location and funding source did not affect RQ for any group. Conclusions: Systemic barriers persist in minority enrollment in PDAC clinical trials. Clinical trial design optimizing inclusive eligibility requirements is a first feasible step in increasing minority clinical trial enrollment. Racial and ethnic representation in pancreatic ductal adenocarcinoma clinical trials. Enrollment Fraction (Median, IQR) Representation Quotient (Median, IQR) NHW 0.28 (0.12-0.62) 1.17 (1.09-1.24) NHB 0.15 (0-0.33) 0.47 (0-0.87) NHAPI 0 (0-0.23) 0 (0-0.45) NHAIAN 0 (0-0) 0 (0-0) Hispanic 0.07 (0-0.21) 0.26 (0-0.68) *Abbreviations: Interquartile Range (IQR), Non-Hispanic Black (NHB), Non-Hispanic Asian/Pacific Islander (NHAPI), Non-Hispanic American Indian/Alaskan Native (NHAIAN).

Impact of education on clinical confidence utilizing HER2-targeted therapies in colorectal cancer.

225 Background: Novel targeted therapies entered the treatment landscape in patients with HER2-positive metastatic colorectal cancer (mCRC). To ensure that these therapies are used effectively, clinicians must assess tumor HER2 status and recognize how HER2-directed treatment modalities fit into the current paradigm. To further enable clinicians to integrate HER2-targeted therapies, an educational program was designed in 2023. Methods: A one-hour online, video-based program was designed for clinicians and their teams and hosted on MedLive from February 2023 for one year. Knowledge and competence questions were administered pre-, and immediate post-activity. Additional questions assessed attitudes, barriers, and intended practice changes related to HER-positive mCRC. Results: Over 4,000 participants engaged in the educational activity, 67% of whom were physicians, and 63% noting their specialty as oncology. Approximately 68% identified as treaters seeing 14 patients with CRC per week with 78% of those patients have HER2-positive CRC. All pre-post questions showed significant improvements in knowledge and competence related to HER2 amplification testing methodologies, trial eligibility criteria, identification of patients who would benefit from anti-HER2 targeted regimens, and adverse events associated with anti-HER2 agents. Following the activity, 51% were more likely to incorporate testing for HER2 expression level or amplification prior to the selection of targeted therapy for their patients. The greatest challenges faced when managing patients with HER2-positive mCRC were affordability of therapy for patients (50%), adherence to treatment schedules (25%) and patient anxiety about treatment efficacy (24%). The most common barriers to patient enrollment in clinical trials identified by clinicians were lack of trials at their institutions (35%), lack of trials in their geographic region (21%), and patient lack of interest (20%). Qualitative insights on intended practice changes were shared by learners post-activity. Conclusions: The outcomes of this educational activity demonstrate the effectiveness of education in improving knowledge and confidence from testing to adverse event management to better integrate new regimens into practice. Encouraging practice changes were also seen from the write-in responses from learners. Additional needs were also identified to further solidify HER2 testing as a prerequisite for anti-HER2 targeted therapies, selecting eligible patients, and timely management of adverse events.

EQUITY GI: A prospective study to enhance quality, inclusivity, and trial participation in Black patients with gastrointestinal cancer.

TPS843 Background: Black individuals, including African Americans, experience a disproportionate cancer burden and exhibit the lowest survival rates among all racial groups for gastrointestinal (GI) cancers. The EQUITY GI study seeks to address the significant health disparities encountered by Black patients with GI cancers in the areas of biomarker testing, evidence-based care, clinical trial participation, and health literacy. Our central hypothesis postulates that a comprehensive approach—encompassing appropriate biomarker testing, ensuring evidence-based treatments, support for clinical trial participation, and health literacy initiatives—is essential to effectively mitigate health disparities among Black patients with GI cancers. Methods: The primary objective of this study is to promote equitable care for Black patients with GI cancers by ensuring appropriate biomarker testing and the delivery of evidence-based care. The secondary objectives include promoting clinical trial participation and enhancing health literacy. The specific goals are to increase the rate of evidence-based care, including biomarker testing, to ≥80%, increase the clinical trial enrollment rate from 5% to 15%, and improve the Cancer Health Literacy Test-30 (CHLT-30) score by 30%. Following a comprehensive assessment of the care gap, several initiatives will be implemented: 1. Tracking biomarker testing through a clinical information tracking tool (EQUITY-GI Oncotracker), 2. Providing guidance to treating providers through a molecular tumor board, 3. Facilitating referrals for clinical trials through navigators, and 4. Implementing health literacy interventions measured by CHLT-30 score. We aim to enroll 200 patients over 18 months. With this expected enrollment, the power to detect a ≥60% absolute improvement in the biomarker testing rate (from the current 20% to the expected ≥80%) is over 98%, using a two-sided chi-square test with a significance level of 0.05. To demonstrate an improvement in the clinical trial enrollment rate from 5% to 15%, 18 black patient will be required to get enrolled in a clinical trial through the referrals generated from the current project. To detect a 30% improvement in the mean CHLT-30 score (17 to 22) following health literacy interventions, at least 120 patients will be required, using a two-sided paired t-test with a significance level of 0.05.

Communication of cancer biomarker testing results: What patients need.

51 Background: As colorectal cancer (CRC) biomarker testing becomes more widespread and important for treatment decisions, understanding testing results can improve patient engagement, shared decision-making, and facilitate clinical trial enrollment. Our experience in the online 12,000+ member CRC community COLONTOWN (CT), suggests that communication of biomarker results to patients is not ideal. To learn more, we surveyed CT members on their biomarker testing experience. Methods: An online survey posted in CT in September 2024 had questions on testing received (what was tested and how), test results experience (communication before testing and after results, patient understanding and resulting impact), suggested provider statements on biomarker results (statements patients prefer) and disease and respondent details. Results: Of 83 respondents, 70% had testing that included at least 3 common CRC biomarkers; the following are results from this group. Until receipt of results, 30% were unaware that biomarker testing was being done, and 56% first reviewed results without a clinician. Only 17% of respondents felt that nothing was lacking in the clinician communication of biomarker testing results. Upon receipt of biomarker test results, respondents’ feelings improved (30%,18%), did not change (63%, 55%) or worsened (7%, 27%) about treatment options and prognosis, respectively. Test results made 51% feel more confident in their care, and reduced stress for 25%, but increased stress for 39%, with 1/3 citing sub-par communication of results as at least partly driving the stress increase. The value of clear communication was evident, as the most appealing sample provider statements on results with no actionable biomarkers included confirmation of proposed treatment plan and clarity on non-actionable biomarkers. Not surprisingly, 58% learned the most about their biomarker results from COLONTOWN. Conclusions: Our survey highlights the gaps in communication of biomarker testing results and provides insights on what may improve them. The perceived value of biomarker test results for patients seem to go beyond actionability as traditionally defined. Context-specific, nuanced communication of “what the results really mean” and a discussion of its impact on patient experience needs to be part of clinician communication of test results. We plan to develop resources to help, and we implore clinicians and testing companies to consider our findings and make changes in how they share test results with patients.

Retrospective study evaluating the genomic landscape of anal squamous cell carcinoma using liquid biopsy.

8 Background: Advanced-stage squamous cell carcinoma of the anus (aSCCA) is a rare malignancy. Diagnostic biopsies are often inadequate for tissue-based genomic profiling, thus genomic profiles are largely unexplored in this setting. We assessed liquid biopsy NGS results of aSCCA patients (pts) and described genomic profiles by age and sex. To our knowledge, we are the first to describe genetic alterations by liquid biopsy in this patient population. Methods: Pts with aSCCA who underwent circulating tumor DNA (ctDNA) NGS with Guardant360 assays from 2017 to 2024 were included. Frequency of alterations were assessed based on sex and age (18-49 years (yrs), ≥50 yrs). Co-occurrence patterns were assessed using cBioPortal. Demographics were extracted from test requisition forms. Statistical analyses via two sided t-tests were performed with significance defined as p<0.05. Results: 646 pts with aSCCA had non-synonymous ctDNA alterations detected; 69.2% (N=447) were female and 30.8% (N=199) male. Median age was 66 yrs (32-94) with 9.9% (N=64) <50 yrs and 90.1% (N=582) ≥50 yrs. Most frequently altered genes were PIK3CA (17.3%), TP53 (9.8%), ATM (7.8%), EGFR (4.3%), and BRCA2 (4.2%). More unique genes were altered in ≥50 yrs cohort [53 mutations, 38 genes with copy number amplification (CNA)] vs <50 yrs cohort (30 mutations, 66 CNA). Most frequent genes altered in <50 yrs cohort were TP53 (17.6%), PIK3CA (13.2%), EGFR (11.0%), APC (4.4%), and MET (4.4%). PIK3CA (16.7%), TP53 (12.2%), ATM (8.8%), BRCA2 (5.5%), and EGFR (3.4%) were most frequent in ≥50 yrs cohort. More genes were altered in females (64 mutations, 32 CNA) vs. males (56 mutations, 41 CNA). Most frequent alterations in females were PIK3CA E545K (3.4%), PIK3CA CNA (2.8%), PIK3CA E542K (1.9%), and ATM CNA (1.0%) vs in male pts being PIK3CA E545K (4.8%), PIK3CA CNA (3.3%), PIK3CA E542K (3.3%), EGFR CNA (1.6%), TERT promoter (1.0%). Overall, PIK3CA and TP53 alterations were mutually exclusive (odds ratio 0.43, p<0.001). Conclusions: Liquid biopsy is feasible in patients with aSCCA. Most frequently detected alterations and CNAs were in PIK3CA and TP53 in aSCCA which is consistent with prior studies evaluating aSCCA tumor NGS in tissue-based assays. Alterations varied across age and sex. PIK3CA E545K and E542K alterations were detected frequently in this population and have on-label therapies for non-aSCCA indications which may be a source for clinical consideration in this cancer type in the future. This data illustrates the importance of liquid biopsy NGS to also screen for clinical trial enrollment in a disease which is poorly responsive to standard therapy. Additional research is warranted to further elucidate genomic profiles for clinical applications of this rare tumor.

Disparities in clinical trial enrollment among LGBTQ+ individuals and its impact on cancer treatment and management: A systematic review.

805 Background: There is a significant gap in oncologic research, which arises from the exclusion of LGBTQ+ individuals from cancer clinical trials, compromising the development of personalized cancer therapies and limiting the generalizability of findings. Despite known health disparities in this population, including higher cancer risk factors and unique psychosocial stressors, data on clinical trial participation remains sparse. This study aims to elucidate the extent of underrepresentation of LGBTQ+ individuals in cancer clinical trials and examine its impact on treatment efficacy, safety, and overall management. Methods: We conducted a systematic review of literature and clinical trial databases, including PubMed, ClinicalTrials.gov, and other registries, focusing on cancer trials from 2010 to 2024. We extracted data on LGBTQ+ enrollment, analyzed demographic inclusivity criteria, and identified barriers to participation. Subgroup analyses evaluated the correlation between LGBTQ+ representation and treatment outcomes, considering variables such as trial design, recruitment strategies, and data collection on sexual orientation and gender identity. The review also examined policy changes and inclusivity initiatives aimed at improving trial access for this community. Results: The review identified a significant underrepresentation of LGBTQ+ individuals in cancer trials, with sexual orientation and gender identity data reported in only 6.2% of trials. Structural and sociocultural barriers, including heteronormative trial designs, lack of inclusive recruitment strategies, and pervasive discrimination, were frequently cited as impediments. Trials that included LGBTQ+ participants rarely conducted stratified analyses to assess differential treatment responses, leading to a paucity of data on drug safety, efficacy, and toxicity profiles specific to this population. The absence of these data may contribute to suboptimal therapeutic decision-making and potential adverse outcomes in clinical practice. Conclusions: The substantial underrepresentation of LGBTQ+ individuals in cancer clinical trials impairs the ability to develop inclusive, evidence-based oncology care. Addressing this gap requires systematic changes, including the integration of sexual and gender minority data collection, implementation of LGBTQ+-specific recruitment frameworks, and stratified analyses of treatment outcomes. Enhancing trial inclusivity will not only improve the external validity of oncologic research but also support the development of tailored therapeutic approaches that address the unique needs of LGBTQ+ cancer patients, ultimately advancing health equity in cancer care.

Extensive molecular profiling of KRAS wild-type as compared to KRAS mutated pancreatic ductal adenocarcinoma on 318 patients.

Molecular profiling is increasingly implemented to guide treatment of advanced pancreatic ductal adenocarcinoma (PDAC), especially when for clinical trials enrollment. This study aimed to describe actionable alterations detected in KRAS mutated (KRASm) versus KRAS wild-type (KRASwt) PDAC, the latter group being considered enriched in molecular alterations. This prospective monocentric study included patients with locally advanced or metastatic PDAC who underwent next-generation sequencing (NGS) on liquid biopsy and/or tissue samples between 2015 and 2023, as part of the BIP academic study (NCT02534649). Actionable alterations were classified using the ESCAT (ESMO Scale for Clinical Actionability of molecular Targets). A total of 378 patients with a PDAC underwent NGS: 73 on tissue samples, 162 on liquid biopsies, and 143 on both tissue and liquid. Liquid biopsies had a 59.3 % performance (181 informative samples out of 305). Among 318 informative NGS samples, 273 (86 %) were KRASm, and 45 (14 %) were KRASwt. Median overall survival (OS) was 19.35 in KRASwt patients and 16.89 months for KRASm patients (HR 0.67, 95 %CI (0.49-0.90), p = 0.02). ESCAT alterations were found in 15.7 % of total population, with 31.1 % in KRASwt tumors and 13.2 % in KRASm tumors. BRCA1/2 mutations were identified in 7.5 % of the population, and one NTRK fusion was found in a KRASwt PDAC. The molecular tumor board considered 71 patients (22.3 %) eligible for early-phase trials, with 14 treated with matched therapy. Although actionable mutations were more frequent in KRASwt tumors, 13.2 % of KRASm PDAC harbored ESCAT alterations, emphasizing the importance of molecular profiling regardless of KRAS status.

Financial toxicity in patients with newly diagnosed hepatocellular carcinoma.

538 Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths and has been associated with significant patient (pt) financial liability, however no study has yet examined pt-reported measures of financial toxicity (FT) in this population. We sought to assess pt-reported FT in newly diagnosed HCC and to identify pt-, disease-, and treatment-related factors associated with FT. Methods: Pts with HCC were recruited prior to treatment initiation during their initial visit at a multidisciplinary liver cancer clinic at a tertiary care center between January 2023-May 2024. The Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT), a validated survey for assessing financial distress in pts with cancer (range, 0-44; lower scores reflect worse financial wellness), was completed by participants during their initial visit. Sociodemographic (age, sex, race, ethnicity, primary language, insurance status, employment status, marital status, highest education completed, household income, living arrangement, home zip code), clinical (Barcelona Clinic Liver Cancer stage, performance status, age-adjusted Charlson comorbidity index, albumin-bilirubin score, presence and etiology of chronic liver disease, Child-Pugh grade, MELD-Na score), and planned treatment (surgery, liver-directed therapy, systemic therapy, clinical trial enrollment) characteristics were evaluated by questionnaires or medical record review. The EORTC QLQ-HCC18 was used to assess pt-reported quality of life (QOL). Area Deprivation Indices were calculated using pts’ home zip codes. Mean COST-FACIT scores were compared using two-sided t test for binary variables and one-way ANOVA for non-binary variables. Results: Among 47 pts enrolled, 35 (74%) completed the COST-FACIT survey. Younger age (<65 vs ≥65 yrs; mean, 20.3 vs 27.8; p=0.05), non-English primary language (non-English vs English; mean, 16.2 vs 26.7; p=0.04), less completed education (high school or earlier vs college or beyond; mean, 23.3 vs 32.0; p=0.02), and worse self-reported QOL (EORTC QLQ-HCC18 score ≥cohort median vs <cohort median; mean, 21.4 vs 29.2; p=0.02) were significantly associated with worse FT. Although not statistically significant, Hispanic ethnicity (Hispanic vs not Hispanic; mean, 16.1 vs 26.4; p=0.07), lack of employment (not employed vs retired vs employed; mean, 15.5 vs 29.4 vs 24.3; p=0.07), and no plan for liver-directed therapy (no vs yes; mean, 17.9 vs 26.7; p=0.07) trended towards worse pt-reported FT. Conclusions: Among pts with newly diagnosed HCC, significantly higher pt-reported FT is associated with younger age, non-English primary language, less completed education, and worse QOL. Efforts are underway to longitudinally follow our study cohort to assess the course of self-reported FT over 1-year follow-up as well as its associations with treatment response and survival.

The impact of a patient advisory board on a clinical comparative effectiveness trial: a comparison of patient and researcher perspectives.

Aim: To examine contributions of a patient advisory board (PAB) to the design and conduct of The Pulmonary Embolism Prevention after Hip and Knee Replacement (PEPPER) Trial (NCT02810704) and compare perceptions of PAB members and researchers on the Trial. Materials & methods This evaluation of the PAB was conducted by Clinical Coordinating Center (CCC) members who first discussed PAB contributions, leading to the design of a semi-structured WebEx interview individually querying PAB members on their experience. Two study team members analyzed transcriptions of the interviews for common themes, which were discussed and affirmed at an in-person meeting with PAB members. Results: The contribution most frequently cited as meaningful by PAB members was the creation of a recruitment video. In contrast, the research team considered the most impactful PAB recommendation to be omission of pneumatic compression boots as a study variable. PAB members spoke highly of their involvement in the trial and emphasized shared decision-making in the patient-physician relationship. Conclusion: Researchers and PAB members had different opinions about which PAB contributions were most impactful to the study. This likely derives from differences in perspective; PAB members focused on patient experience and the patient-surgeon relationship while researchers focused primarily on trial outcomes. PAB contributions led to two major protocol changes that had a substantial positive effect on trial design, recruitment and enrollment. This evaluation adds to the engagement literature, which contains little on what patients think of their involvement in the design and conduct of clinical research studies and will aid in encouraging treatment preference discussions between patient and surgeon, thereby supporting the goal of improved patient outcomes.

Efficacy, immunogenicity, and safety of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine.

In this phase 3 trial of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine (RSVPreF3-Mat), a higher rate of preterm birth was observed in the vaccine (6.8%) versus the placebo group (4.9%). Trial enrollment and vaccination were stopped. Results of investigations into this safety signal were reported previously. Here, we describe end-of-trial efficacy, immunogenicity, and safety results. Women 18-49 years old were randomized 2:1 to receive one dose of RSVPreF3-Mat (n=3557) or placebo (n=1771) at 240/7-340/7 weeks' gestation. Primary outcomes were any and severe medically assessed RSV-associated lower respiratory tract disease (MA-RSV-LRTD) in infants until 6 months post-birth and safety until 12 months post-birth. Other efficacy outcomes were evaluated, along with immunogenicity (until 6 months post-partum/birth) and safety in mothers and infants. Efficacy in infants until 6 months post-birth was 65.5% (95% credible interval: 37.5-82.0) against any MA-RSV-LRTD, 69.0% (33.0-87.6) against severe MA-RSV-LRTD, and 50.1% (-3.6-75.8) against RSV hospitalization; it waned over time thereafter. Efficacy against MA-RSV-LRTD was 47.8% (-25.8-77.3) in low- and middle-income and 75.9% (46.1-91.5) in high-income countries. RSVPreF3-Mat induced a substantial increase in RSV-A neutralization titers in mothers, with efficient transplacental transfer of antibodies that persisted in infants until at least 6 months post-birth. Consistent with the high titers of transplacentally transferred antibodies, this trial suggests a reduced risk of any/severe MA-RSV-LRTD and RSV hospitalization until 6 months post-birth in infants born to mothers immunized with RSVPreF3-Mat during pregnancy. However, vaccine development was terminated due to an identified preterm birth risk. ClinicalTrials.gov: NCT04605159.

Impact of Race/Ethnicity on Clinical and Genomic Characteristics, Trial Participation, and Genotype-Matched Therapy among Patients with Metastatic Breast Cancer.

Race/ethnicity may affect outcomes in metastatic breast cancer (MBC) due to biological and social determinants. We evaluated the impact of race/ethnicity on clinical, socioeconomic, and genomic characteristics, clinical trial participation, and receipt of genotype-matched therapy among patients with MBC. A retrospective study of patients with MBC who underwent cell-free DNA testing (cfDNA, Guardant360â, 74 gene panel) between 11/2016 and 11/2020 was conducted. Receipt of genotype-matched therapy targeted at a cfDNA actionable mutation was determined. Pearson's chi-squared and Wilcoxon rank-sum tests were used to compare categorical and continuous variables between groups. Multivariable logistic regression was used to assess the association of race and receiving matched therapy. 425 patients with MBC and cfDNA results were identified (White: 369, Black: 27, Hispanic 15, and Asian 14). White patients traveled further for cancer care than other groups (p<0.001). White patients had the highest rates of commercial insurance, Black patients had the highest rates of state-supported insurance, and Asian patients had the highest uninsured rates (p<0.001). Clinical trial enrollment did not differ by race/ethnicity (p=0.34). The proportion of patients with ≥1 actionable mutation in cfDNA did not vary by race/ethnicity (p=0.18). The highest rates of matched therapy were observed in White patients (p<0.001). After multivariable logistic regression adjusting for subtype, commercial vs. other insurance, Charlson comorbidity index, and distance to center, White patients remained more likely to receive matched therapy (p=0.024). Racial/ethnic minority patients were less likely to receive matched therapy. Further research is needed to identify barriers to precision medicine.

Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC.

Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited. We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment. Predicted superpopulations included African (AFR, N=153), Admixed American (AMR, N=222), East Asian (EAS, N=67), European (EUR, N=968), and South Asian (SAS, N=42). Reported race and ethnicity and ancestry-based genetic superpopulations were non-randomly associated (p<0.001). Patients with an atypical teratoid rhabdoid tumor or meningioma were enriched for AFR ancestry (OR=2.6, FDR=0.01; OR=2.9, FDR=0.01, respectively). Among KIAA1549::BRAF fusion-positive low-grade glioma (LGG) diagnoses, EAS and SAS patients disproportionately harbored exon 15:09 breakpoints (FDR<0.05), and AMR patients demonstrated rare breakpoints, which were associated with lesser degree of surgical resection and worse event free survival (EFS) versus other breakpoints (HR=4.6, p=0.03). Non-EUR and AMR patients with germ cell tumors and SHH-activated medulloblastoma, respectively, exhibited worse EFS relative to EUR patients (HR=12.1, p<0.01; HR=5.2, p=0.03) and AFR patients with LGG (HR=16.4, p<0.01) or ependymoma (HR=5.5, p=0.02) had worse overall survival compared to EUR patients. We observed higher frequency of clinical trial enrollment among AMR patients across tumor histologies (OR=2.0, p=<0.01), but increased utilization of photon versus proton radiation relative to other superpopulations (OR=0.55, p=0.04). Genetic ancestry-associated differences exist across pediatric CNS tumor histological and molecular subtypes from PBTA and PNOC. Further investigation into genetic and socioeconomic factors contributing to these observed inequities is needed.

Racial and ethnic enrollment disparities in clinical trials leading to FDA approvals for gynecologic malignancies.

Black women and other minorities have higher age adjusted incidence risk for cervical and endometrial cancer than White women. However, the extent of racial and ethnic disparities in clinical trial enrollment among studies performed mainly in North America and Europe for gynecologic malignancy is unknown. This study analyzed enrollment rates by race/ethnicity in trials that led to Food and Drug Administration (FDA) approvals for gynecological cancers from 2010 to 2024. This cross-sectional study examined clinical trials registered with ClinicalTrials.gov that resulted in new FDA approvals for gynecologic malignancies between 2010 and 2024. Exclusion criteria were studies not conducted in North America or Europe. Enrollment fractions were obtained by dividing the number of trial participants segregated by the racial/ethnic group by the corresponding U.S. cancer prevalence (uterine, ovarian, and cervical cancer) for 2016-2020 for each racial/ethnic group. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to compare enrollment fractions of minority groups to non-Hispanic (NH) Whites. A total of 31 studies met the inclusion criteria, with 21 reporting race/ethnicity data. Three (3/21) studies dichotomized race as NH-White and Non-White, and Seven (7/21) reported ethnicity. The median number of participants was 494 [interquartile range 150-674]. Fifteen studies were phase III, and six were phase IB/II trials. Treatments included immune checkpoint inhibitors (seven studies), PARP inhibitors (five), VEGF inhibitors (four), antibody-drug conjugates (four), and an imaging marker (one). Across all studies, 11,258 patients were included, 5,563 (49.4%) in ovarian cancer studies, 2,963 (26.3%) in endometrial cancer studies, and 2,732 (24.3%) in cervical cancer studies. Three studies (n=1,734) dichotomized participants into NH-White and Non-White (NH-White 1,291 [74.4%] and Non-White 443 [25.6%], and enrollment fractions were 0.51% for NH-White and 0.43% for No-White, with Non-White being underrepresented odds ratio (OR) 0.85. 95% confidence interval (CI) [0.76-0.95], p=.004. In an Analysis of 18 studies reporting race categories, NH-Black patients were significantly underrepresented (OR 0.50, 95% CI [0.45-0.54], p<.001), while Asian patients were overrepresented (OR 2.81, 95% CI [2.64-2.99], p<.001). In the four studies reporting ethnicity, Hispanic patients were also significantly underrepresented (OR 0.69, 95% CI [0.61-0.78], p<.001). In clinical trials, performed in North America and Europe mainly, leading to FDA approvals for gynecologic malignancies - NH-Black and Hispanic patients are significantly underrepresented compared to NH-White participants when enrollment is benchmarked to the U.S. female population with gynecological cancer. These trials do not adequately reflect the U.S. populations diagnosed with these malignancies. Enrollment strategies to increase diversity are urgently needed to ensure clinical trial results are equitable and applicable across all populations. Efforts from the American Society of Clinical Oncology, the Association of Community Cancer Centers, and the Gynecologic Oncologic Group / Society of Gynecologic Oncology Inclusion, Diversity, Equity and Access initiative provide a comprehensive framework for achieving this goal.

P0588 Efficacy and health-related quality of life associated with second-line vedolizumab after one prior first-line anti-tumour necrosis factor treatment in patients with active ulcerative colitis: A meta-analysis of the GEMINI-1 and VISIBLE-1 trials

Abstract Background Vedolizumab (VDZ) is a monoclonal antibody approved for adults with moderately to severely active ulcerative colitis (UC) and an inadequate response/intolerance to conventional therapy or anti-tumour necrosis factor (TNF) treatment. There is published evidence supporting the use of VDZ as a first-line biologic in patients with UC, but additional efficacy data for second-line VDZ (after first-line anti-TNF treatment) are required to define its optimal position in the treatment sequence. We conducted a meta-analysis of the efficacy and health-related quality of life (HRQoL) associated with second-line VDZ treatment exposure in patients with UC using data from the randomized, placebo (PBO)-controlled phase 3 GEMINI-1/VISIBLE-1 trials. Methods GEMINI-1 (NCT00783718) evaluated intravenous (IV) VDZ as induction/maintenance treatment in patients with active UC.1 VISIBLE-1 (NCT02611830) assessed IV/subcutaneous maintenance VDZ in patients with moderately/severely active UC.2 Patients who received first-line anti-TNF treatment within 5 years before trial enrolment were included in the meta-analysis. The primary outcome was clinical remission (defined as Adapted Mayo Score [AMS] 1 or 2; Figure). Secondary outcomes included corticosteroid-free remission, mucosal healing and HRQoL (measured via the Inflammatory Bowel Disease Questionnaire and EuroQoL-5 Dimension Visual Analogue Scale). Outcomes were assessed at Week 52. Study-specific treatment effects were estimated using generalized linear models. Efficacy of VDZ vs PBO was compared using fixed-effects models. Regression analyses assessed treatment effects, adjusting for disease location/duration and previous corticosteroid use. Results In total, 137 patients from GEMINI-1/VISIBLE-1 were included (VDZ, n=89; PBO, n=48). Patient characteristics were similar across cohorts, but the mean (standard deviation) disease duration ranged from 6.6 (4.4) years (GEMINI-1 VDZ IV cohort) to 9.9 (10.1) years (VISIBLE-1 PBO cohort). Second-line VDZ was associated with a higher likelihood of achieving clinical remission (AMS 1 and 2; Figure) and all secondary outcomes, including improved HRQoL, at Week 52 vs PBO (Table). Regression analysis showed that patients treated with VDZ were 11.35 (95% confidence interval 3.25–39.63) times more likely to achieve clinical remission (defined as AMS 1) vs PBO. Conclusion Second-line VDZ after first-line anti-TNF treatment significantly increased the likelihood of achieving clinical remission, mucosal healing and improved HRQoL at Week 52 vs PBO in patients with UC. The small sample size and heterogeneity observed in some outcomes warrant further research to strengthen these findings.

Intervention With Concentrated Albumin for Undifferentiated Sepsis in the Emergency Department (ICARUS-ED): A Pilot Randomized Controlled Trial.

Concentrated albumin early in sepsis resuscitation remains largely unexplored. Objectives were to determine 1) feasibility of early intervention with concentrated albumin in emergency department (ED) patients with suspected infection and hypoperfusion and 2) whether early albumin therapy improves outcomes. ED patients with suspected infection and hypoperfusion (systolic blood pressure [SBP]<90 mmHg or lactate ≥4.0 mmol/L) were randomized to receive either 400 mL 20% albumin over 4 hours or no albumin. All patients were treated with crystalloids, antibiotics, and other therapies at the treating team's discretion. Primary outcome was SBP at 24 hours; secondary outcomes included SBP at 6 hours, fluid and organ support requirements, organ dysfunction, and mortality. Quantile and logistic regressions were used to calculate differences (and 95% CI) between study groups. Compliance with study protocol was more than 95%, and infection was confirmed in 95% of the 464 study patients enrolled. SBP at 24 hours did not differ between intervention (110.5 mmHg) and standard care arms (110 mmHg). In patients treated with albumin, SBP was higher at 6 hours, less total fluid was infused at 72 hours, fewer patients required vasopressor therapy at 24 and 72 hours, and organ function was improved. Mortality was not significantly different. Early identification, trial enrollment, and intervention in ED patients with sepsis is feasible. In this pilot study, concentrated albumin given early in resuscitation did not improve SBP at 24 hours. Albumin was associated with less total fluid and vasopressor requirements and improved organ dysfunction. A multicenter study is indicated.

Insights From Diverse Perspectives on Social Media Messages to Inform Young Adults With Cancer About Clinical Trials: Focus Group Study.

Low rates of adolescent and young adult (YA; aged 15-39 y) clinical trial enrollment (CTE), particularly among underserved groups, have resulted in a lack of standardized cancer treatments and follow-up guidelines for this group that may limit improvement in cancer treatments and survival outcomes for YAs. To understand and address unique barriers to CTE, we conducted focus groups to learn about informational, financial, and psychosocial needs of YAs surrounding CTE and identify strategies to address these barriers. We conducted 5 focus groups in 2023 among a diverse sample of YA patients from across the United States. An interview guide was developed collaboratively with YA advocates. Specifically, informational needs, financial concerns, and psychosocial issues were explored, and participants were probed to suggest strategies, especially those that leverage technology, to address these barriers. Sessions were audio recorded, transcribed, and coded using direct content analysis. Findings were synthesized through consensus discussions. We confirmed the previously proposed thematic barriers regarding YA CTE and identified 9 subthemes: awareness, lack of clear and accessible CTE information, fear of the unknown, assumptions about costs, insurance coverage, navigating financial responsibilities, clinical trial discussions, clinical trial misconceptions, and desire for a support network. Throughout, YAs mentioned needs that might be addressed through informational outreach leveraging digital technology, the internet, and social media. This study expands knowledge of YA perceived barriers to CTE. These findings suggest that leveraging digital technology to disseminate reliable information to address needs may be an effective strategy to improve clinical trial participation in the YA population.

Implementation of artificial intelligence approaches in oncology clinical trials: A systematic review.

There is a growing interest in leveraging artificial intelligence (AI) technologies to enhance various aspects of clinical trials. The goal of this systematic review is to assess the impact of implementing AI approaches on different aspects of oncology clinical trials. Pertinent keywords were used to find relevant articles published in PubMed, Scopus, and Google Scholar databases, which described the clinical application of AI approaches. A quality evaluation utilizing a customized checklist specifically adapted was conducted. This study is registered with PROSPERO (CRD42024537153). Out of the identified 2833 studies, 72 studies satisfied the inclusion criteria. Clinical Trial Enrollment & Eligibility were among the most commonly studied clinical trial aspects with 30 papers. The prediction of outcomes was covered in 25 studies of which 15 addressed the prediction of patients' survival and 10 addressed the prediction of drug outcomes. The trial design was studied in 10 articles. Three studies addressed each of the personalized treatments and decision-making, while one addressed data management. The results demonstrate using AI in cancer clinical trials has the potential to increase clinical trial enrollment, predict clinical outcomes, improve trial design, enhance personalized treatments, and increase concordance in decision-making. Additionally, automating some areas and tasks, clinical trials were made more efficient, and human error was minimized. Nevertheless, concerns and restrictions related to the application of AI in clinical studies are also noted. AI tools have the potential to revolutionize the design, enrollment rate, and outcome prediction of oncology clinical trials.