Clinical Trial Populations Research Articles

Defining demographic cohorts in clinical trial populations using large electronic health records databases

The Food and Drug Administration (FDA) has stressed the need to ensure that clinical trial study populations accurately reflect the patients likely to use the product, if approved. However, the FDA has not provided specific guidance on how clinically relevant demographic characteristics might be defined. Therefore, the present study was designed to develop a framework that could be used to rapidly identify population demographics for any medical condition. Then, these real-world data were used as the basis to calculate acceptable demographic parameters (with 95% confidence intervals) for clinical trial populations. Data on Alzheimer's Disease were used as an example of the proposed approach.

Historical efforts to develop 99mTc-based amyloid plaque targeting radiotracers.

Imaging biomarkers have changed the way we study Alzheimer's disease and related dementias, develop new therapeutics to treat the disease, and stratify patient populations in clinical trials. With respect to protein aggregates comprised of amyloid-β plaques and tau neurofibrillary tangles, Positron Emission Tomography (PET) has become the gold standard imaging modality for quantitative visualization. Due to high infrastructural costs, the availability of PET remains limited to large urban areas within high income nations. This limits access to leading edge medical imaging, and potentially access to new treatments, by millions of rural and remote residents in those regions as well as billions of people in middle- and low-income countries. Single Photon Emission Computed Tomography (SPECT) is a more widely available imaging alternative with lower infrastructural costs and decades of familiarity amongst nuclear medicine professionals. Recent technological advances have closed the gap in spatial resolution and quantitation between SPECT and PET. If effective SPECT radiotracers were available to visualize amyloid-β plaques, geographic barriers to imaging could be circumvented. In this review, we will discuss past efforts to develop SPECT radiotracers targeting amyloid-β plaques which incorporate the most used radionuclide in nuclear medicine: technetium-99m (99mTc; t 1/2 = 6.01 h; γ = 140 keV). While reviewing the various chemical scaffolds and chelates employed, the focus will be upon the impact to the pharmacological properties of putative 99mTc-based amyloid-targeting radiotracers.

Disparities in access to translational research

Translational research describes the process of applying observations and scientific discoveries made in the laboratory to clinical applications that can improve the health of individual patients, most often through clinical trials. To apply the findings of translational research studies to the broader population, the study population must accurately reflect the group of patients afflicted by a particular disease. Yet, it is well known that significant disparities exist for underrepresented groups and lower socioeconomic populations in clinical trials. In fact, only 20% of randomized controlled studies published in high-impact oncology journals include subgroup analyses to assess differences in outcomes based on race or ethnicity.1 If effective interventions to decrease health disparities in research are to be implemented, it is critical to understand the multifactorial influences that create such differences. These are complex and include individual patient factors, family and social support, provider and organizational factors, as well as policy and community factors. Patient access to tertiary or quaternary care academic centers or designated cancer centers with the funding and resources to carry out translational research and knowledge of ongoing available research endeavors is often critical. Active community engagement and outreach and deep understanding of a particular health system's catchment area are necessary to increase both awareness and participation in clinical trials. Without significant progress in biomedical research patient recruitment, existing racial and ethnic health disparities will be challenging to overcome.

Immunotherapy After Chemotherapy and Radiation for Clinical Stage III Lung Cancer

The 2017 international PACIFIC trial established a role for immunotherapy after chemoradiation for unresectable stage III non-small cell lung cancer (NSCLC). However, in the US, patients with NSCLC commonly differ from clinical trial populations in terms of age, health, access to care, and treatment course, which may all factor into the efficacy of immunotherapy. To determine the outcomes of immunotherapy use in unresectable stage III NSCLC in the general US population. This cohort study analyzed the National Cancer Database for patients diagnosed with clinical stage III NSCLC between 2015 and 2017 with follow-up through the end of 2018 who were treated with chemotherapy and radiation. Data were analyzed January 2022. Mortality hazard in a multivariable Cox proportional hazards model and survival among a propensity-matched sample treated with chemotherapy and radiation, with and without immunotherapy. A total of 23 811 patients with clinical stage III NSCLC with median (IQR) age 66 (59-72) years met inclusion criteria (10 454 [43.9%] women; 564 [2.4%] Asian, 2930 [12.3%] Black, 20 077 [84.3%] White patients), including 209 (16.1%) patients with multiple comorbidities and 1297 (5.4%) immunotherapy recipients. Immunotherapy after chemotherapy and radiation was associated with reduced mortality (hazard ratio [HR], 0.74; 95% CI, 0.67-0.82; P < .001). Among a propensity-matched sample, immunotherapy was associated with superior 3-year survival (52% [1297 patients at 0 months, 56 patients at 36 months] vs 44% [2594 patients at 0 months, 173 patients at 36 months]; P < .001). The treatment of 833 patients who received immunotherapy (64.2%) differed from the PACIFIC trial protocol, including 221 patients (17.0%) who received radiation doses outside of the protocol range and 731 patients (56.4%) who started immunotherapy more than 6 weeks after radiation was completed. The survival advantage of immunotherapy persisted when initiated up to 12 weeks after radiation was completed (HR, 0.75; 95% CI, 0.61-0.92). Among patients who received radiation outside the PACIFIC protocol range, the survival advantage of immunotherapy was not significant (HR, 0.87; 95% CI, 0.69-1.01). In this cohort study, immunotherapy after chemotherapy and radiation for stage III NSCLC was associated with a survival advantage in the general US population despite two-thirds of patients treated differently than the PACIFIC protocol. The findings suggest there may be flexibility in the timing of immunotherapy initiation after radiation; further study is warranted to clarify the clinical benefits of immunotherapy.

Key barriers against racial and ethnic minority participation in U.S. clinical trials

&lt;p class="abstract"&gt;Despite the United States’ (U.S.) longstanding history of promoting a melting pot nation of people from diverse racial and ethnic backgrounds all capable of achieving the American Dream, it is argued that the U.S. is failing to deliver high quality healthcare to all of its constituents equally. The widely seen health disparities of ethnic minority groups endure has extended into the parallel field of clinical research and clinical trials. There is a staggering gap between the percentage of White clinical trial participants compared to clinical trial participants of racially and ethnically diverse minority groups in U.S. clinical trials. Underrepresentation of minority groups in clinical trials dismisses opportunities to identify potential serious sub-group safety or efficacy signals, open doors to access life-saving treatments, and ultimately improve the standard of evidence-based medicine in the United States. Current literature on this issue frequently reiterates the following five key barriers underrepresented minority groups face against clinical trial participation: mistrust, lack of awareness and access, cultural and language barriers, investigator and provider bias, and financial burdens. A deeper dive into understanding each barrier will be critical in implementing changes with actions and in perspectives in order to address the issue of poor racial and ethnic representation in clinical trial populations.&lt;/p&gt;

Leveraging a Previously Published Population Pharmacokinetic Model to Predict Rivaroxaban Exposure in Real-World Patients.

Population pharmacokinetic (PK)/pharmacodynamic models are commonly used to inform drug dosing; however, often real-world patients are not well represented in the clinical trial population. We sought to determine how well dosing recommended in the rivaroxaban drug label results in exposure for real-world patients within a reference area under the concentration-time curve (AUC) range. To accomplish this, we assessed the utility of a prior published rivaroxaban population PK model to predict exposure in real-world patients. We used the model to predict rivaroxaban exposure for 230 real-world patients using 3 methods: (1) using patient phenotype information only, (2) using individual post hoc estimates of clearance from the prior model based on single PK samples of rivaroxaban collected at steady state without refitting of the prior model, and (3) using individual post hoc estimates of clearance from the prior model based on PK samples of rivaroxaban collected at steady state after refitting of the prior model. We compared the results across 3 software packages (NONMEM, Phoenix NLME, and Monolix). We found that while the average patient-assigned dosing per the drug label will likely result in the AUC falling within the reference range, AUC for most individual patients will be outside the reference range. When comparing post hoc estimates, the average pairwise percentage differences were all &lt;10% when comparing the software packages, but individual pairwise estimates varied as much as 50%. This study demonstrates the use of a prior published rivaroxaban population PK model to predict exposure in real-world patients.

Identifying and overcoming barriers to participation of minority populations in clinical trials: Lessons learned from the VanDAAM study.

Participation in cancer research trials by minority populations is imperative in reducing disparities in clinical outcomes. Even with increased awareness of the importance of minority patient inclusion in clinical research to improve cancer care and survival, significant barriers persist in accruing and retaining minority patients into clinical trials. This study sought to identify and address barriers to minority accrual to a minimal risk clinical research study in real-time.

Strategies to Increase Participation of African Populations in Clinical Trials

Conducting clinical research in low- and middle-income countries is essential to address the global impact of cancer. In 2017, ASCO convened an Academic Global Oncology Task Force that recommended an increase in global oncology research to enhance the field of oncology through research and education. The emerging crisis of cancer in Africa demands a similar global commitment to workforce development, infrastructure building, and access to care that will provide a platform for impactful and relevant research efforts. In the words of the African Organisation for Research and Training in Cancer, it is time to "transform cancer control in Africa through collaboration in education, research, (and) delivery of equitable and timely interventions to minimize the impact of cancer." Although there are some initiatives aimed at developing research capacity to host trials in Africa, there is now a need to establish strategic partnerships with the aim of achieving harmonized, accredited clinical trial units capable of running trials according to Good Clinical Practice standards.

Gold Coast criteria expand clinical trial eligibility in amyotrophic lateral sclerosis.

Consensus criteria to formalize the diagnosis of amyotrophic lateral sclerosis (ALS) and refine clinical trial populations have evolved. The recently proposed Gold Coast consensus criteria are intended to simplify use and increase sensitivity. We aimed to evaluate the potential impact of these criteria on clinical trial eligibility. We performed a single-center, retrospective study of people diagnosed with ALS between 2016 and 2021 to determine the numbers of those meeting Gold Coast, revised El Escorial (rEEC) criteria, and Awaji criteria. We identified the proportion of those who would have been eligible for participation in three major ALS clinical trials if Gold Coast were used in place of rEEC definite/probable criteria. (rEEC D/P). Two hundred six people with ALS were included in our study. 48.5% met Gold Coast criteria but not rEEC D/P. Using the Gold Coast criteria would result in higher rates of clinical trial eligibility after other inclusion criteria were met: 95.2% vs 42.5% (P < .001) in a phase III study of riluzole; 100% vs 31.0% (P=.002) in a phase III study of edaravone; and 95.6% vs 45.3% (P < .001) in an ongoing phase III study of sodium phenylbutyrate and taurursodiol. The sensitivity of the Gold Coast criteria (96.1%; 95% confidence interval [CI],92.2%-98.2%) was significantly higher than that of rEEC D/P (47.6%; 95% CI, 40.6%-54.6%; for difference, χ2 =117.6; P < .001). Until robust biomarkers are available to diagnose ALS, consensus diagnostic criteria remain necessary. Gold Coast criteria would expand research and clinical trial eligibility and improve external validity of clinical trial results.

Leveraging Clinical Trial Populations and Data from the Children's Oncology Group for Cancer Survivorship Research.

Children and adolescents diagnosed with cancer can now expect an average 85% 5-year overall survival, with significant improvements in longer-term morbidity and mortality reported over the past several decades. However, the long-term impact of therapeutic agents and modalities introduced in recent years remains unclear and will require dedicated follow-up in the years ahead. The Children's Oncology Group (COG), a part of the NCI's National Clinical Trials Network, with over 200 sites across North America and beyond, enrolls more than 10,000 patients onto research protocols annually, inclusive of first-line clinical trials and nontherapeutic studies. COG provides a platform to conduct survivorship research with several unique strengths: (i) a huge catchment to ascertain relatively rare but important adverse events, (ii) study populations that are otherwise too rare to study in smaller consortia, including access to highly diverse patient populations, (iii) long-term follow-up of clinical trial populations linked to the original trial data, and (iv) a natural platform for intervention research. Enhancements in COG infrastructure facilitate survivorship research, including a COG patient registry (Project:EveryChild), availability of a long-term follow-up tracking resource, and successful deployment of various remote-based study procedures to reduce the burden on participants and participating institutions.

Patterns of venous thromboembolism risk, treatment, and outcomes among patients with cancer from uninsured and vulnerable populations.

The epidemiology of cancer-associated thrombosis (CAT) among uninsured and vulnerable populations in the US is not well-characterized. We performed a retrospective cohort study for patients with newly diagnosed cancer from 2011 to 2020 at Harris Health System, which cares for uninsured residents in the Houston metropolitan area. Patient demographics, NCI comorbidity index, area of deprivation index (ADI), cancer histology, staging, and systemic therapy data were extracted. CAT included overall venous thromboembolism (VTE) or pulmonary embolism +/- lower extremity deep vein thrombosis (PE/LE-DVT) within 1 year of diagnosis. We used multivariable Fine-Gray models to assess the associations with CAT accounting for death as a competing risk. Among 15 342 patients, 74% were uninsured and 84% lived in socioeconomically disadvantaged neighborhoods. There were 16% Non-Hispanic White (NHW), 28% Non-Hispanic Black (NHB), 50% Hispanic (27% Mexican), and 6% Asian/Pacific Islanders (API). The 1-year CAT incidence rate was 14.6%. Overall VTE was lower for Hispanics versus NHW (SHR 0.87 [0.76-0.99]) and API versus NHW (SHR 0.58 [0.44-0.77]). PE/LE-DVT was higher for NHB versus NHW (SHR 1.18 [1.01-1.39]). CAT was also associated with chemotherapy-based regimens (+/- immunotherapy), age, obesity, cancer type/staging, VTE history, and recent hospitalization. NCI comorbidity and ADI scores were associated with mortality but not CAT. In a large cohort of underserved patients with cancer, we identified an elevated incidence of CAT with known and novel risk predictors. Hispanics had lower adjusted rates of CAT and mortality. Our findings highlight the need to investigate and incorporate vulnerable populations in clinical trials.

Abstract 5930: Identifying effective communication for recruitment of minority women to a breast cancer prevention study: A novel focus group approach

Abstract Ensuring that minoritized women are involved in breast cancer research is important to address well-documented current disparities in cancer incidence, stages of diagnosis, and mortality rates. This study used a novel interactive focus group method to identify innovative communication strategies for recruiting women from two minority groups—Latinas and Asian Americans—into the Komen Tissue Bank, a specific breast cancer biobank clinical trial. Through activities that employed visual interactive tools to facilitate group discussion and self-reflection, the authors examined perspectives and motivations for Asian American women (N=17) and Latinas (N=14) toward donating their healthy breast tissue. Findings included three themes that, while common to both groups, were unique in how they were expressed: lack of knowledge concerning breast cancer risks and participation in clinical research, cultural influences in breast cancer risk thinking, and how altruism relates to perceived personal connection to breast cancer. More significantly, this study illuminated the importance of using innovative methods to encourage deeper, more enlightened participation among underrepresented populations that may not arise in a traditional focus group format. The findings from this study will inform future health communication efforts to recruit women from these groups into clinical research projects like the Komen Tissue Bank. These findings also illustrate the importance of applying rigorous qualitative work to supplement quantitative research to increase the inclusion of minoritized populations in clinical trials. Citation Format: Katherine E. Ridley-Merriweather, Stephanie M. Younker, Madeline D. Evans, Cynthia Y. Wu. Identifying effective communication for recruitment of minority women to a breast cancer prevention study: A novel focus group approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5930.

Abstract 494: Role of age, BMI, and tumor subtype in racial/ethnic disparities in breast cancer survival: A pooled analysis of four Alliance adjuvant clinical trials

Abstract Background: Previous studies have demonstrated poorer survival of Black women with breast cancer. We assessed whether race/ethnicity was associated with disease-free (DFS) and overall survival (OS) among women with breast cancer enrolled in clinical trials for early-stage breast cancer according to tumor subtype, age, and body mass index (BMI). Methods: 10,011 women enrolled in one of four adjuvant chemotherapy trials: CALGB 9741, CALGB 49907, CALGB 40101, or NCCTG N9831. 9918 participants had available DFS and/or OS data and were included in the analysis. Cox models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between race/ethnicity and DFS and OS. We compared Non-Hispanic (NH) Black (n=871), Hispanic (n=436), and other race participants (n=283) to NH Whites (n=7889). We assessed associations within strata of age group (&amp;lt;50, 50-&amp;lt;65, or ≥65), tumor subtype (hormone receptor (HR)+/HER2-, HR-/HER2+, or HR-/HER2-), and BMI (&amp;lt;25, 25-&amp;lt;30, or ≥30). Results: In multivariable-adjusted models, NH Black patients under 50 years of age had worse DFS compared to NH White patients (HR: 1.34, 95% CI: 1.10-1.62) and worse OS (HR: 1.64, 95% CI: 1.30-2.07). The differences in DFS and OS persisted in patients ages 50 to &amp;lt;65, though there were no significant differences in DFS or OS between NH Black and NH White patients ages ≥65. Among Hispanic and NH White participants, younger age at diagnosis was associated with greater DFS compared with older age overall while this was not true for NH Black patients. Among patients with HR+/HER2- tumors, NH Black patients when compared to NH White patients had worse DFS (HR 1.33, 95% CI: 1.04-1.70) but there was not a significant difference in OS (HR 1.35, 95% CI: 1.00-1.83). DFS and OS for other tumor subtypes did not significantly differ by race. Among patients with BMI &amp;lt;25, NH Black patients had significantly worse DFS (HR: 1.70, 95% CI: 1.25-2.30) and OS (HR:1.76, 95% CI:1.20-2.58) compared to NH White patients. There was no difference in survival between different race/ethnicity groups among individuals with BMI ≥25. Conclusions: Our results identified subgroups that may contribute to the observed disparities in survival between NH Black and NH White women with early-stage breast cancer. The greatest disparities are among individuals &amp;lt;50 years of age, those with HR+/HER2-, and those with BMI &amp;lt;25. These differences exist even within clinical trial populations with similar initial therapy, suggesting that disparities may be influenced by inequities in survivorship care and long-term treatment, such as endocrine therapy adherence and persistence, and/or differences in tumor or host biology. Support: U10CA180821 and U10CA180882; ClinicalTrials.gov Identifiers: NCT00003088, NCT00005970, NCT00024102, NCT00041119; https://acknowledgments.alliancefound.org Citation Format: Marla Lipsyc-Sharf, Karla V. Ballman, Jordan D. Campbell, Hyman B. Muss, Edith A. Perez, Lawrence N. Shulman, Lisa A. Carey, Ann H. Partridge, Erica T. Warner. Role of age, BMI, and tumor subtype in racial/ethnic disparities in breast cancer survival: A pooled analysis of four Alliance adjuvant clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 494.

Diversity, inclusion, and patient (pt)-centricity in the randomized, double-blind, phase III ASTEFANIA study of ado-trastuzumab emtansine (T-DM1) ± atezolizumab in pts with HER2-positive early breast cancer (EBC) with residual invasive disease after preoperative chemotherapy and anti-HER2 therapy.

e12504 Background: Representative pt populations in clinical trials are essential to address healthcare disparities between different racial/ethnic groups, including treatment access and pt outcomes. Many clinical trials mainly include White pts, which may limit the generalizability of the results to the global population. A framework that was recently developed by Genentech for improving inclusion of underrepresented pt groups, as well as the CHIMES (NCT04377555) and EMPACTA (NCT04372186) studies, have all shown the feasibility of inclusive studies. ASTEFANIA (NCT04873362) is a pt-centric study, which includes pt/investigator collaboration to keep a pt focus and tactics to recruit a diverse population and enable participation of underserved communities. We report early recruitment data. Methods: Global/local initiatives and inclusive eligibility criteria remove barriers to enrollment of underserved pts and support treatment journeys. Eligible pts (Eastern Cooperative Oncology Group performance status of 0/1; no prior immune checkpoint inhibitor treatment) are randomized 1:1 to T-DM1 (3.6 mg/kg) + atezolizumab (1200 mg)/placebo every 3 weeks for 14 cycles (stratification factors: clinical stage, hormone receptor status, preoperative anti-HER2 therapy, PD-L1 status). Primary endpoints: IDFS in intention-to-treat and PD-L1-positive populations. Secondary endpoints include overall survival, patient-reported outcomes (PROs), and safety. To remove pt access barriers and ease pt burden, consent and PRO forms are available in multiple languages, mobile nursing/telemedicine is planned for pts in rural areas, a wellness app and culturally sensitive support videos are being created, and financial support is provided for study-related expenses and loss of earnings. Results: Recruitment began in May 2021. By Feb 9, 2022, 236 pts were randomized: 147 White (62%), 72 Asian (31%; Indian [n = 4], Korean [46], Chinese [16], other [6]), 10 Hispanic (4%; 5 of whom also identify as American Indian), 2 Black (1%), and 5 pts (2%) whose race/ethnicity was unreported/unknown. Of these, 27 (11%) have received financial support. Enrollment in Africa begins later this year. Mobile nursing/telemedicine is planned for 14 countries. Conclusions: As the first study of its kind in HER2-positive EBC, ASTEFANIA actively aims to be accessible and include pts from a range of races/ethnicities and socially underserved backgrounds. There is a growing need for more compassionate and inclusive research. To do this, forward planning of pt-centric studies is essential to reduce the burden on study resources. We hope that the tactics outlined here will allow us to achieve our goals of inclusive research. Clinical trial information: NCT04873362.

Comparison of sociodemographic characteristics of a phase 1 clinical trial population at an NCI-designated comprehensive cancer center in the Southeast to catchment area.

e18591 Background: Racial and ethnic minority populations are consistently under-represented in oncology clinical trials despite comprising a disproportionate share of cancer burden. Due in part to difficulties associated with participation, phase 1 trials pose a unique challenge and opportunity for minority inclusion. Here we examine the sociodemographics of phase 1 clinical trial patients at an NCI-designated Comprehensive Cancer Center compared to all patients treated at the center, patients with new cancer diagnoses in metropolitan Atlanta, and the state of Georgia (GA). Methods: Patients enrolled on phase 1 trials at the Winship Cancer Institute (WCI) from 2015-2020, identified from a data warehouse, were compared to new patient registrations at WCI from 2015-2019. Patients with cancer in metro Atlanta and GA were identified from the Surveillance, Epidemiology, and End Results (SEER) Program: Nov 2018 Submission. Covariates for the phase 1 and institutional cohort included sex, race, ECOG PS, insurance, and age at consent. Covariates for SEER patients included sex, race, and age at diagnosis. Summary statistics are reported for categorical variables using frequencies and percentages, and for continuous variables using mean, median, standard deviation, and range. One-sample proportion tests were utilized to compare observed demographic proportions on phase 1 trials with proportions calculated from new patient registrations at WCI and from SEER case data. Results: From 2015-2020, 2325 patients (43.4% F, 56.6% M) signed consent for phase 1 trials. Grouped race distribution was 70.3% White, 26.2% Black, 3.5% Other. Insurance distribution was 42.9% private, 48% government, 9.1% uninsured/other. Mean age at consent was 61.7 years (MD 63, ran 19-92). Of new patient registrations at WCI in 2015 ( N= 12358) (49.7% F, 50.3% M), grouped race distribution was 64.0% W, 28.2% B, 8% O. Atlanta 2015 SEER patients ( N= 31101) (50.3%F, 49.7%M) showed grouped race distribution 58.4% W, 37.2% B, 4.3% O. Mean age at diagnosis was 62.9. GA 2015 SEER patients ( N= 99487) (48.6%F, 51.4%M) showed grouped race distribution 71.2% W, 26.7% B, 2.1% O. Mean age at diagnosis was 64.2. The race and sex distribution of phase 1 patients was significantly different than proportions calculated from new patient registrations at WCI and SEER data from patients in Atlanta ( p&lt; 0.001). Sex distribution was significantly different than GA SEER patients. Conclusions: Phase 1 patients were significantly more likely to be white and male, compared with patients treated at the cancer center, as well as patients with cancer in Atlanta. Race distribution was not significantly different from patients with cancer in GA. Our intent is to characterize existing disparities in order to increase representation of patients from racial and ethnic minority backgrounds in phase 1 clinical trials.

Racial/ethnic disparities in locoregional recurrence in hormone-receptor positive node-negative breast cancer patients enrolled in the TAILORx trial.

515 Background: Whether racial/ethnic disparities in locoregional recurrence (LRR) exist in patients (pts) with similar access to care treated on clinical trials is uncertain. We examined racial/ethnic differences in LRR in hormone-receptor positive HER2-negative (HR+HER2-) node-negative pts enrolled in the TAILORx trial. Methods: 10,273 pts age 18-75 were enrolled in TAILORx, which assigned pts with an OncotypeDx Recurrence Score (RS) &lt;11 to endocrine therapy (ET) alone, those with RS &gt;25 to chemotherapy + ET (CET), and randomized pts with RS 11-25 to ET or CET. Pts with unknown race/ethnicity (n=323) or incomplete treatment adherence information (n=1,168) were excluded from this analysis. Race/ethnicity was self-reported. LRR was defined as ipsilateral invasive in-breast, chest wall, or regional nodal recurrence without distant recurrence. Kaplan-Meier curves were used to estimate 8-year LRR. Cox proportional hazards analysis adjusted for clinical and treatment factors was used to determine factors associated with LRR. Results: 8,782 pts with T1-2N0 HR+HER2- breast cancer were included. Race/ethnicity was non-Hispanic White (NHW) in 6,932 (78.9%), non-Hispanic Black (NHB) in 629 (7.2%), Hispanic in 818 (9.3%), and Asian in 403 (4.6%). Treatment adherence was high across groups over time, with a 9.1% crossover in treatment arms. Average duration of ET was 63.8 +/- 0.3 months. Radiation therapy was planned in 96.0% of pts after breast conservation and 12.7% after mastectomy. At a median follow-up of 8 years, LRR rates were 1.9% in NHW, 4.2% in in NHB, 3.2% in Hispanic, and 3.9% in Asian pts (p&lt;0.01). LRR rates broken down by RS are shown in the Table. On adjusted analyses, NHB and Asian (vs. NHW) pts were more likely to have LRR (HR 1.94 for NHB, HR 2.04 for Asian, p&lt;0.05 for both). Additional statistically significant factors associated with LRR included age &lt;50 (HR 1.85), T2 tumors (HR 1.43), higher grade (HR 2.30 for grade 3), and high RS (HR 3.13 for RS&gt;25). Treatment receipt (chemotherapy, ET duration, and radiation) was not associated with LRR in this population. Conclusions: Racial/ethnic differences in LRR were seen in T1-2N0 HR+HER2- breast cancer pts enrolled in the TAILORx trial despite high rates of treatment adherence in this clinical trial population, with highest LRR rates in NHB and Asian pts. Further study in needed to understand racial/ethnic patterns in LRR by breast cancer subtype and if failure to rescue after LRR may contribute to differences in breast cancer mortality.[Table: see text]

A binational cancer registry analysis of Hispanic patients in Mexico and the United States.

e22513 Background: A marked disparity in cancer burden exists between regions of the world. This global picture can only be obtained because of data obtained from population-based cancer registries, which allow estimates for different geographic areas. We investigate the data differences, clinical characteristics, tumor information, and patient outcomes of Hispanic patients in North America. Methods: We used data from Mexico’s National Cancer Registry and the United States Surveillance, Epidemiology, and End Results Program (SEER) program with four years of follow-up on each registry. of Mexican registry, we excluded outliers and records with more than 80% missing variable; of the United States registry, only patients identified as hispanic or latino were included. On the Mexican registry we re-coded all variables and the United States registry data on secondary neoplasm was excluded to match boths registry. Baseline characteristics and a geographical information system was constructed to map cancer registries and their relative frequencies. A survival analysis was done to understand the correlation between covariates. Lastly, we build machine learning models to predict 3-year overall survival. Results: The Hispanic cancer database (HCB) consists of 291,178 patients (19,904 from Mexico, and 271,274 from the United States). The top three most frequent cancer types were breast, prostate and hematological. The age of diagnosis was 55±17 years. Mexico has a slight skewness towards the earlier age of diagnosis of females. The registries with the highest burden of cancer were New Mexico (USA) and Baja California Sur (Mexico). Average survival months seem very stable across registries in the United States, but not in Mexico. Our linear regression model achieved a coefficient of determination (R-squared) of 0.49, while the logistic regression achieved an AUC of 0.82, with an F1-score of 0.88. Conclusions: Cancer registries are important tools for prevention and development of control programs. Hispanics are a traditionally neglected population in oncological clinical trials, with low enrollment of patients outside of the United States. Mexico enacted its National Cancer Registry Law in 2017, which alongside the Hispanic data on the SEER program in the United States offers enormous opportunities for continued collaboration and understanding of cancer. Both Mexico and the United States can strengthen their cancer prevention strategies and generate trans-border collaboration, research, and patient-support networks.

P.047 Implications of Gold Coast Criteria in diagnosis of amyotrophic lateral sclerosis in a large subspecialty clinic

Background: Criteria to formalize the diagnosis of amyotrophic lateral sclerosis (ALS) and refine clinical trial populations have evolved. The recently proposed Gold Coast criteria (GCC) are intended to simplify use and increase sensitivity. We evaluated sensitivity of GCC and potential impacts on therapeutic trial enrollment. Methods: We performed a single center retrospective study including patients diagnosed with ALS between 2016 – 2021. We determined criteria met at diagnosis according to revised El Escorial (rEEC), Awaji (AC) and GCC. We compared sensitivity and examined impacts GCC would have on enrollment in landmark ALS trials. Results: We included 203 people with ALS. Sensitivity of GCC (96.1%, 95% confidence interval [CI] = 92.2-98.2%) was significantly higher than rEEC (89.8%, 95% CI 84.6-93.4%, χ2 = 5.3, p = 0.01) and AC (89.3%, 95% CI 84.1-93.0%, χ2 = 6.1, p = 0.006). GCC was more sensitive than clinically definite or probable rEEC (47.6%, 95% CI 40.6-54.6%, χ2 = 117.6, p = &lt; 0.001) and use would result in increased eligibility in landmark therapeutic trials. Conclusions: GCC are more sensitive than rEEC and AC at time of diagnosis in ALS. Use of GCC in our population would expand clinical trial participation and make results more widely generalizable.

Idecabtagene vicleucel (Ide-cel) chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory multiple myeloma (RRMM): Real-world experience.

8042 Background: Ide-cel, a BCMA directed CAR T-cell therapy, was FDA approved 3/26/2021 for the treatment of RRMM after 4 prior lines of therapy. We evaluated the real-world outcomes of patients treated with standard of care ide-cel under the commercial FDA label. Methods: Ten US academic centers contributed data to this effort independent of the manufacturer. As of 1/10/2022, 138 patients were leukapheresed with overall manufacturing failure in 6 (4%). 108 patients were infused ≥ 30 days prior to data-cut off and constitute the study population for this retrospective analysis. Results: Table describes the study population compared to the pivotal KarMMa-1 trial (Munshi et al, NEJM 2021). Patients in our study were less likely to have ECOG PS of 0/1 (77%) and more likely to be penta-refractory (41%). 67% of patients would not have met eligibility criteria for KarMMa. Common reasons for ineligibility (&gt; 1 reason in 22% patients) were co-morbidities (28%), cytopenias (22%), prior therapy with alloSCT/CAR-T/other BCMA therapy (19%), CNS myeloma/non-measurable disease/plasma cell leukemia (13%), and fitness (12%). 81% of patients received bridging therapy. Toxicity was comparable to that seen in KarMMa-1. Cytokine release syndrome (CRS) was seen in 82% (&gt; grade 3: 4%) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 15% (&gt; grade 3: 5%) of patients, respectively. Tocilizumab and steroids were used in 72% and 25% of patients, respectively. Infections were seen in 34% of patients. Day 30 response was evaluable in 104 patients. Response rates were: ≥ partial response, 83%; ≥ very good partial response, 64%; and ≥ complete response (CR), 34%. 11% of patients have died by data cut-off, 7 due to disease progression and 5 due to other causes (1 grade 5 CRS, 1 hemophagocytic lymphohistiocytosis, 1 progressive neurological weakness, 2 COVID-19). Conclusions: This multicenter retrospective study delineates the real-world outcomes of ide-cel CAR T-cell therapy for RRMM. Despite more patients being penta-refractory and less fit compared to the pivotal KarMMa trial, safety and 30-day responses in the real-world setting (overall response rate: 83%, CR: 34%) are comparable to the clinical trial population. Follow-up is ongoing and updated data will be presented. [Table: see text]

034 Updated safety analysis of ocrelizumab in multiple sclerosis

BackgroundOngoing safety reporting is crucial to understanding the long-term benefit-risk profile of ocrelizumab in multiple sclerosis (MS). Safety/efficacy of ocrelizumab have been characterised in Phase II (NCT00676715) and III (NCT01247324/NCT01412333/NCT01194570) trials in relapsing-remitting MS, relapsing MS (RMS) and primary progressive MS (PPMS). Here, we report safety evaluations from ocrelizumab clinical trials and open-label extensions up to January 2019, and selected post-marketing data.MethodsSafety outcomes are reported for the ocrelizumab all-exposure population in Phase II/III and ongoing Phase IIIb trials. To account for different exposure lengths, rates per 100 patient years (PY) are presented.ResultsIn clinical trials, 4,611 patients with MS received ocrelizumab (14,329 PY exposure). Reported rates per 100 PY (95% confidence interval) were: adverse events (AEs), 252 (249–254); serious AEs, 7.33(6.89–7.79); infections, 76.7 (75.3–78.2); serious infections, 1.99 (1.77–2.23); malignancies, 0.46 (0.35–0.58); and AEs leading to discontinuation, 1.08 (0.92–1.27). Updated ocrelizumab all-exposure population data and selected post-marketing data will be presented.ConclusionsReported event rates in the ocrelizumab all-exposure clinical trial population and post-mar- keting settings remain generally consistent with the controlled treatment period in RMS/PPMS populations. Regular reporting of long-term safety data will continue.k.schmierer@qmul.ac.uk