Clinical Trial Populations Research Articles

Assessment of COVID-19 progression on day 5 from symptoms onset

BackgroundA major limitation of current predictive prognostic models in patients with COVID-19 is the heterogeneity of population in terms of disease stage and duration. This study aims at identifying a panel of clinical and laboratory parameters that at day-5 of symptoms onset could predict disease progression in hospitalized patients with COVID-19.MethodsProspective cohort study on hospitalized adult patients with COVID-19. Patient-level epidemiological, clinical, and laboratory data were collected at fixed time-points: day 5, 10, and 15 from symptoms onset. COVID-19 progression was defined as in-hospital death and/or transfer to ICU and/or respiratory failure (PaO2/FiO2 ratio < 200) within day-11 of symptoms onset. Multivariate regression was performed to identify predictors of COVID-19 progression. A model assessed at day-5 of symptoms onset including male sex, age > 65 years, dyspnoea, cardiovascular disease, and at least three abnormal laboratory parameters among CRP (> 80 U/L), ALT (> 40 U/L), NLR (> 4.5), LDH (> 250 U/L), and CK (> 80 U/L) was proposed. Discrimination power was assessed by computing area under the receiver operating characteristic (AUC) values.ResultsA total of 235 patients with COVID-19 were prospectively included in a 3-month period. The majority of patients were male (148, 63%) and the mean age was 71 (SD 15.9). One hundred and ninety patients (81%) suffered from at least one underlying illness, most frequently cardiovascular disease (47%), neurological/psychiatric disorders (35%), and diabetes (21%). Among them 88 (37%) experienced COVID-19 progression. The proposed model showed an AUC of 0.73 (95% CI 0.66–0.81) for predicting disease progression by day-11.ConclusionAn easy-to-use panel of laboratory/clinical parameters computed at day-5 of symptoms onset predicts, with fair discrimination ability, COVID-19 progression. Assessment of these features at day-5 of symptoms onset could facilitate clinicians’ decision making. The model can also play a role as a tool to increase homogeneity of population in clinical trials on COVID-19 treatment in hospitalized patients.

Establishing the content validity of the Epworth Sleepiness Scale for Children and Adolescents in Prader-Willi syndrome.

Excessive daytime sleepiness is common in Prader-Willi syndrome (PWS), with prevalence ranging from 52% to 100%. The goal of this study was to establish the content validity (ie, evidence that an instrument measures an intended concept of interest) of the parent/caregiver version of the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), a measure of daytime sleepiness, in PWS. Qualitative, dyadic semistructured video interviews were conducted with 18 caregivers and their children with PWS from April to June 2020. Concept elicitation and cognitive interview techniques were implemented. Thematic analyses allowed for examination of themes and data patterns. All caregivers (mean age 49 years) were mothers of individuals with PWS who experienced troublesome daytime sleepiness (mean age 14 years). The most prevalent observable signs/symptoms of daytime sleepiness were sleepy/sleepiness (n = 17; 94.4%), tired/tiredness (n = 16; 88.9%), exhaustion/exhausted (n = 5; 27.8%), anxious/stressed (n = 5; 27.8%), irritable/frustrated (n = 5; 27.8%), having tantrums/outbursts (n = 5; 27.8%), and lethargy (n = 4; 22.2%). Daytime sleepiness impacted various aspects of health including mental, emotional, physical, and social well-being. When caregivers were asked about the activities associated with daytime sleepiness, all salient concepts elicited mapped to the ESS-CHAD; saturation was met after the first 4 interviews. Only 2 concepts, after physical exertion and while inactive/bored, did not map. Caregiver statements indicated that these concepts, although related to daytime activities, were atypical of daily routines. The ESS-CHAD was well understood and relevant to caregivers. This study supports the content validity of the ESS-CHAD and its appropriateness for evaluating treatment efficacy of daytime sleepiness in PWS. Patel VP, Patroneva A, Glaze DG, Davis K, Merikle E, Revana A. Establishing the content validity of the Epworth Sleepiness Scale for Children and Adolescents in Prader-Willi syndrome. J Clin Sleep Med. 2022;18(2):485-496.

Improving the enrollment of women and racially/ethnically diverse populations in cardiovascular clinical trials: An ASPC practice statement

Cardiovascular disease (CVD) remains the leading cause of death for both women and men worldwide. In the United States (U.S.), there are significant disparities in cardiovascular risk factors and CVD outcomes among racial and ethnic minority populations, some of whom have the highest U.S. CVD incidence and mortality. Despite this, women and racial/ethnic minority populations remain underrepresented in cardiovascular clinical trials, relative to their disease burden and population percentage. The lack of diverse participants in trials is not only a moral and ethical issue, but a scientific concern, as it can limit application of future therapies. Providing comprehensive demographic data by sex and race/ethnicity and increasing representation of diverse participants into clinical trials are essential in assessing accurate drug response, safety and efficacy information. Additionally, diversifying investigators and clinical trial staff may assist with connecting to the language, customs, and beliefs of study populations and increase recruitment of participants from diverse backgrounds. In this review, a working group for the American Society for Preventive Cardiology (ASPC) reviewed the literature regarding the inclusion of women and individuals of diverse backgrounds into cardiovascular clinical trials, focusing on prevention, and provided recommendations of best practices for improving enrollment to be more representative of the U.S. society into trials.

Diversity and Inclusion in Pancreatic Cancer Clinical Trials

Diversity and Inclusion in Pancreatic Cancer Clinical Trials

TRLS-04. A Nomogram for Predicting Survival in Patients with Brain Metastases

BackgroundBrain metastases are the most common intracranial tumors in adults, with a very poor prognosis, and poses distinct clinical challenges. This study aimed to develop a more accurate prognostic nomogram for predicting overall survival (OS) of patients with Brain Metastases.MethodsWe conducted a retrospective analysis of 1062 patients with brain metastases at the Sun Yat-sen University Cancer Center (SYSUCC, Guangzhou, China) between January 2010 and January 2018, Among them, 331 patients underwent surgery to remove brain metastases. Kaplan–Meier analysis was performed to screen for potential clinical variables that could be used to establish the nomogram for predicting overall survival.ResultsWe found that age,gender, whether to remove intracranial lesions, radiotherapy, ECOG were independent prognostic factors for predicting the overall survival with brain metastases,and surgical resection for brain metastatic lesions could significantly improve OS,but only in certain groups of patients with brain metastases can benefit from intracranial lesion resection, such as no extracranial metastasis. And patients with brain metastases whose primary tumor is lung adenocarcinoma or breast cancer are more likely to benefit from surgery in terms of overall survival time.A nomogram for predicting 1- and 2-year overall survival rates was constructed, which exhibited good accuracy in predicting overall survival.ConclusionThrough statistical analysis, we have found the factors related to the surgical benefit of patients with brain metastases, and established a prognostic nonogram,This nomogram may be used to guide individual treatments and in selecting an appropriate patient population for clinical trials.

25754 Presence of psoriatic arthritis has no impact on the clinical efficacy and safety of secukinumab in patients with psoriasis: Pooled analysis of the phase 3 CLEAR and CLARITY trials

Background: In this updated analysis using a recent pooled clinical trial population, we examined the incremental burden of comorbid psoriatic arthritis (PsA) on the clinical efficacy and safety of secukinumab vs ustekinumab among patients with moderate to severe plaque psoriasis.

A Framework for Systematic Assessment of Clinical Trial Population Representativeness Using Electronic Health Records Data.

Clinical trials are the gold standard for generating robust medical evidence, but clinical trial results often raise generalizability concerns, which can be attributed to the lack of population representativeness. The electronic health records (EHRs) data are useful for estimating the population representativeness of clinical trial study population. This research aims to estimate the population representativeness of clinical trials systematically using EHR data during the early design stage. We present an end-to-end analytical framework for transforming free-text clinical trial eligibility criteria into executable database queries conformant with the Observational Medical Outcomes Partnership Common Data Model and for systematically quantifying the population representativeness for each clinical trial. We calculated the population representativeness of 782 novel coronavirus disease 2019 (COVID-19) trials and 3,827 type 2 diabetes mellitus (T2DM) trials in the United States respectively using this framework. With the use of overly restrictive eligibility criteria, 85.7% of the COVID-19 trials and 30.1% of T2DM trials had poor population representativeness. This research demonstrates the potential of using the EHR data to assess the clinical trials population representativeness, providing data-driven metrics to inform the selection and optimization of eligibility criteria.

P 38. Mild cognitive impairment in patients with Parkinson's disease is characterized by a strong coupling of EEG signal complexity and band power

Introduction. Mild cognitive impairment (MCI) in Parkinson“s disease (PD) has been recognized as a transitional state between normal cognition (PD-NC) and overt dementia (PD-D) and is associated with an increased risk of conversion toward PD-D. In a cross-sectional setting the combination of spectral band power and signal complexity for use as a diagnostic biomarker for assessing MCI in early stages of PD is evaluated. Patients & Methods. 30 PD-NC individuals (13 females, medians: age 67.5 yrs., edu. 14 yrs., UPDRS 16, LED 507.5, disease duration 33 mos.) were compared with 9 individuals diagnosed with PD-MCI matched for age, sex and education (4 females, medians: age 66.0 yrs., edu 16 yrs., UPDRS 15, LED 770.0, disease duration 40 mos.). High-density EEG recordings were obtained during eyes open (EO) and eyes closed (EC) condition. Signal complexity, quantified based on Tsallis entropy (TE) [1], as well as relative band power (rBP) were evaluated for the delta, theta, alpha, beta and gamma band. For all bands and conditions, the Pearson correlation between TE and rBP was calculated for each individual. The resulting correlation scores were then compared across groups according to an individuals“ diagnosis. Results. TE and rBP analyzed independently, showed no significant differences between PD-NC and PD-MCI. However, in combination, significant differences were observed: Compared to PD-NC, most patients with PD-MCI showed significantly higher correlation of TE and rBP in both the alpha band (8-13Hz) in EO condition as well as the beta band (13-30Hz) in EC condition. The corrected p-values in both cases were p<0.05. Furthermore, in case of PD-MCI, the median correlation was negative: -0.33 (alpha band, EO) and -0.50 (beta band, EC). For PD-NC individuals, median correlation was positive: 0.11 (alpha band, EO) and 0.09 (beta band, EC). Other bands, in either condition, showed no significant group differences in correlation between TE and Rbp. Conclusion/Discussion. In conclusion, signal complexity and relative band power provide, in combination, a candidate diagnostic biomarker for MCI in PD. Higher correlation in case of PD-MCI indicates a reduced ability of the cortex to modify signal complexity independently of relative band power. The results apply to groups, and may help to define study populations for clinical trials, but cannot be applied in their present form for individual treatment decisions or counselling. Reference [1] Sneddon R. The Tsallis entropy of natural information. Physica A Statistical and Theoretical Physics 2007; 386: 101–118. Fig. 1.

Autologous Hematopoietic Stem Cell Transplantation in Active Multiple Sclerosis: A Real-world Case Series.

To examine outcomes in people with multiple sclerosis (PwMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) in a real-world setting. This was a retrospective cohort study of PwMS treated with AHSCT at 2 centers in London, UK, consecutively between 2012 and 2019 who had ≥6 months of follow-up or died at any time. Primary outcomes were survival free of multiple sclerosis (MS) relapses, MRI new lesions, and worsening of Expanded Disability Status Scale (EDSS) score. Adverse events rates were also examined. The cohort includes 120 PwMS; 52% had progressive MS (primary or secondary) and 48% had relapsing-remitting MS. At baseline, the median EDSS score was 6.0; 90% of the evaluable cases showed MRI activity in the 12 months preceding AHSCT. Median follow-up after AHSCT was 21 months (range 6-85 months). MS relapse-free survival was 93% at 2 years and 87% at 4 years after AHSCT. No new MRI lesions were detected in 90% of participants at 2 years and in 85% at 4 years. EDSS score progression-free survival (PFS) was 75% at 2 years and 65% at 4 years. Epstein-Barr virus reactivation and monoclonal paraproteinemia were associated with worse PFS. There were 3 transplantation-related deaths within 100 days (2.5%), all after fluid overload and cardiac or respiratory failure. Efficacy outcomes of AHSCT in this real-world cohort are similar to those reported in more stringently selected clinical trial populations, although the risks may be higher. This study is rated Class IV because of the uncontrolled, open-label design.

The Development and Use of an EHR-Linked Database for Glomerular Disease Research and Quality Initiatives

Background and Objective: The use of electronic health record (EHR) data can facilitate efficient research and quality initiatives. The imprecision of ICD-10 codes for kidney diagnoses has been an obstacle to discrete data-defined diagnoses in the EHR. This manuscript describes the Kidney Research Network (KRN) registry and database that provide an example of a prospective, real-world data glomerular disease registry for research and quality initiatives. Methods: KRN is a multicenter collaboration of patients, physicians, and scientists across diverse health-care settings with a focus on improving treatment options and outcomes for patients with glomerular disease. The registry and data warehouse amasses retrospective and prospective data including EHR, active research study, completed clinical trials, patient reported outcomes, and other relevant data. Following consent, participating sites enter the patient into KRN and provide a physician-confirmed primary kidney diagnosis. Kidney biopsy reports are redacted and uploaded. Site programmers extract local EHR data including demographics, insurance type, zip code, diagnoses, encounters, laboratories, procedures, medications, dialysis/transplant status, vitals, and vital status monthly. Participating sites transform data to conform to a common data model prior to submitting to the Data Analysis and Coordinating Center (DACC). The DACC stores and reviews each site’s EHR data for quality before loading into the KRN database. Results: As of January 2021, 1,192 patients have enrolled in the registry. The database has been utilized for research, clinical trial design, clinical trial end point validation, and supported quality initiatives. The data also support a dashboard allowing enrolling sites to assist with clinical trial enrollment and population health initiatives. Conclusion: A multicenter registry using EHR data, following physician- and biopsy-confirmed glomerular disease diagnosis, can be established and used effectively for research and quality initiatives. This design provides an example which may be readily replicated for other rare or common disease endeavors.

Long-term risk of death and recurrent cardiovascular events following acute coronary syndromes.

Estimates of the risk of recurrent cardiovascular events (residual risk) among patients with acute coronary syndromes have largely been based on clinical trial populations. Our objective was to estimate the residual risk associated with common comorbidities in a large, unselected, population-based cohort of acute coronary syndrome patients. 31,056 ACS patients (49.5%-non-ST segment elevation myocardial infarction [NSTEMI], 34.0%-ST segment elevation myocardial infarction [STEMI] and 16.5%-unstable angina [UA]) hospitalised in Alberta between April 2010 and March 2016 were included. The primary composite outcome was major adverse cardiovascular events (MACE) including: death, stroke or recurrent myocardial infarction. The secondary outcome was death from any cause. Cox-proportional hazard models were used to identify the impact of ACS type and commonly observed comorbidities (heart failure, hypertension, peripheral vascular disease, renal disease, cerebrovascular disease and diabetes). At 3.0 +/- 3.7 years, rates of MACE were highest in the NSTEMI population followed by STEMI and UA (3.58, 2.41 and 1.68 per 10,000 person years respectively). Mortality was also highest in the NSTEMI population followed by STEMI and UA (2.23, 1.38 and 0.95 per 10,000 person years respectively). Increased burden of comorbidities was associated with an increased risk of MACE, most prominently seen with heart failure (adjusted HR 1.83; 95% CI 1.73-1.93), renal disease (adjusted HR 1.52; 95% CI 1.40-1.65) and diabetes (adjusted HR 1.51; 95% CI 1.44-1.59). The cumulative presence of each of examined comorbidities was associated with an incremental increase in the rate of MACE ranging from 1.7 to 9.98 per 10,000 person years. Rates of secondary prevention medications at discharge were high including: statin (89.5%), angiotensin converting enzyme inhibitor/angiotensin receptor blocker (84.1%) and beta-blockers (85.9%). Residual cardiovascular risk following an acute coronary syndrome remains high despite advances in secondary prevention. A higher burden of comorbidities is associated with increased residual risk that may benefit from aggressive or novel therapies.

Abstract CT156: Radiologic scoring method to define the therapeutic response and surgical candidacy

Abstract Purpose: The purpose of this study is to define the best CT perfusion analytical method for the surgical candidacy of pancreatic cancer patients in Neo-Adjuvant treated clinical trial population. Experimental Design: Study was designed to assess tumor perfusion status. This prospective study involved 24 adult patients with pancreatic adenocarcinoma (PDAC). Inclusion criteria included, patients with histologically or cytologically confirmed resectable, borderline resectable, or locally advanced (unresectable) PDAC. All patients received neoadjuvant therapy (paricalcitol, paclitaxel protein bound, cisplatin and gemcitabine) for up to 6 months Multi-phase CT was performed for most patients on a GE scanner using a standard pancreatic cancer protocol including a pre-injection phase, arterial phase, and porto-venous phase. The iodinated contrast agent Isovue 370 was dosed at 150 cc + 40 cc saline, and injected at a rate of 5 cc/sec into the antecubital vein. Volumetric analysis of images from 24 patients was conducted using 3D imaging software and perfusion scoring assessment was done on each case using 2D and 3D methodology. Regions of interest were drawn to define the volumetric tumor quantification. This work looked at the difference in density between arterial and venous phases, using the Marley equation. This data was then used to assess treatment response and ultimately whether or not a patient would be a surgical candidate. This surgical candidacy of these patients was defined by the “R” score. Results: The R score defines the number of vessels with tumor involvement. Each vessel that had any amount of tumor involvement was scored with a 1. Any patient with a score of 6 or higher was deemed not eligible for surgery while a score of 5 or less was eligible for surgery. 3D Tumor volumetric assessments were performed for the assessment of the treatment response that linked directly with the tumor perfusion.Conclusion: CT vessel perfusion using the R score method could be helpful to define the surgical candidacy of pancreatic cancer patients along with 3D tumor volumetric quantification. Citation Format: Syed Rahmanuddin, Daniel Von Hoff, Derek Cridebring, Jordyn Brase, Yuman Fong, Pejman Motarjem, Ron Korn, Kevin Choong, William Boswell, Erkut Borazanci. Radiologic scoring method to define the therapeutic response and surgical candidacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT156.

Comparison of Overall Survival Associated with Lenalidomide+Dexamethasone and Bortezomib+Dexamethasone Among Relapsed/Refractory Multiple Myeloma Patients: A Matched Analysis of Real World and Clinical Trial Populations

Background: Bortezomib or lenalidomide, in combination with dexamethasone, have been the dominant treatment options for multiple myeloma (MM) over the past decade, both in the frontline and later lines of treatment. Little evidence exists regarding how survival outcomes associated with each of these treatment modalities in a clinical trial (CT) setting compare with those observed in a real-world (RW) setting.Objectives: To compare OS outcome of relapsed refractory MM patients receiving lenalidomide+dexamethasone (Rd) or bortezomib+dexamethasone (Vd) in the RW versus CT settings.Methods: Patients in two RW data sources - SEER-Medicare and Optum™ integrated databases 1) with an index ICD-9 diagnosis code for MM any time from January 1, 2007 until December 31, 2013, 2) aged ≥ 18 years and 3) with no concurrent primary cancers or previous diagnosis of cancer during the 365-day lookback period prior to index diagnosis were included in the study. Lines of treatment (LOTs) were identified based on business rules centered on continuity and concurrence of drug usage. CT data were sourced from the POLLUX trial (for Rd patients) and from the CASTOR trial (for Vd patients). In the post-frontline (i.e., LOT2+) setting, Rd (and Vd) patient instances in the RW population were matched with CT patients on the basis of covariates identified as significant predictors of OS in the respective cohorts. Rd patient instances were matched on the basis of age, gender, prior exposure status to lenalidomide, prior exposure status to a proteasome inhibitor (PI), refractory status to PI and number of prior lines of treatment. Vd patient instances were matched on the basis of age, gender, prior exposure status to an immunomodulatory drug (IMiD), prior exposure status to PI, refractory status to IMiD and number of prior lines of treatment. 1:1 matching was achieved for the CT cohorts from among the RW cohorts. The covariates used for matching and OS of the Rd and Vd cohorts were compared between the RW and CT populations after matching.Results: The size of the RW cohorts used for matching were 789 and 722 for Rd and Vd, respectively; the size of the corresponding CT cohorts were 283 and 247. In the matched Rd cohort (n=566), prior exposure status to lenalidomide and age were significantly different (p<0.05) between the RW and CT populations (Table 1). In the Vd matched cohort (n=494), refractory status to IMiD and age were significantly different (p<0.05) between the RW and CT populations (Table 2). For both of the treatment modalities, the RW and CT populations had similar OS (HR = 1.26, 95% CI = 0.86-1.84 in Rd (Figure 1), and HR = 1.19, 95% CI = 0.84-1.70 in Vd (Figure 2)).Conclusions: In this matched analysis,the outcomes in relapsed refractory MM patients receiving Rd or Vd in the RW setting were similar to those of the CT patients. The benefit of adding a third agent observed in the CT setting may apply to the RW setting as well. [Display omitted] DisclosuresNooka:Amgen, Novartis, Spectrum, Adaptive tecnologies: Consultancy. Voorhees:Oncopeptides: Consultancy; Amgen: Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy; Janssen: Consultancy, Speakers Bureau; Novartis: Consultancy. Kumar:Skyline: Honoraria; Celgene, Millennium, BMS, Onyx, Janssen, Noxxon, AbbVie, Amgen, Merck, Oncopeptides, Skyline Diagnostics, Takeda: Consultancy; Celgene, Millennium/Takeda, Onyx, AbbVie, Janssen, Sanofi, Novartis, Amgen, Genentech, Merck, Oncopeptides, Roche, Skyline Diagnostics: Research Funding. Mehra:Janssen: Employment. Lam:Janssen: Employment. Slavcev:Janssen: Employment. Potluri:SmartAnalyst Inc.: Employment; Janssen: Consultancy, Research Funding. Dasgupta:SmartAnalyst Inc.: Employment; Janssen: Research Funding.

Predicting Response to BET Inhibitors Using a Computational Model and Its Validation: A Beat AML Project Study

Predicting Response to BET Inhibitors Using a Computational Model and Its Validation: A Beat AML Project Study

Weight and weight control behaviors during long-term endometrial cancer survivorship: Results of the Laparoscopic Approach to Cancer of the Endometrium long-term follow-up study.

BackgroundOverweight or obesity is common in endometrial cancer (EC). This study aimed to examine sociodemographic, clinical, and psychosocial characteristics associated with being discontent with current weight and use of weight control methods among long‐term EC survivors.MethodsWomen diagnosed with early‐stage EC who participated in the Laparoscopic Approach to Cancer of the Endometrium (LACE) trial (n = 516) were invited to complete a long‐term follow‐up survey at least 4.5 years after treatment. Chi‐square test and multivariate logistic regression models adjusted for time since surgery were used to determine factors associated with being discontent with current weight.ResultsOn average 9 years after surgery, 190/259 (73%) of participants were currently discontent with their weight, and 146 (56%) had used one or more weight loss methods during the past 12 months. Women who were discontent with their weight were more likely to be younger than 70 years (p < 0.000), and used one or more weight loss methods ever or during the past 12 months (p < 0.000). Among the weight loss methods used, exercise (40.1%), meal reductions (52.7%), or fat/sugar reductions (48.5%) were much more commonly reported than fasting (2.6%) or designated weight loss programs (2.3%).ConclusionsOur study provides evidence that the majority of long‐term EC survivors in this clinical trial population are discontent with their weight and over half continue to use multiple methods to lose weight each year. These data indicate that health professionals and lifestyle educators need to assess weight issues, and develop a tailored plan to address the specific needs of long‐term survivors to assist them become content with their weight after treatment for EC.

The effect of prior cancer on non-small cell lung cancer trial eligibility.

ObjectivesApproximately 20% of patients diagnosed with non‐small cell lung cancer (NSCLC) have a history of prior (non‐lung) cancer. Patients with prior cancer are frequently excluded from clinical trials. We aimed to assess the potential impact of prior cancer on commonly used clinical trial endpoints.Materials and MethodsClinical trials of systemic therapy for incurable NSCLC from clinicaltrials.gov were reviewed to determine the frequency of exclusion on the basis of prior cancer. A cohort of patients with incurable NSCLC and prior cancer, treated with first‐line systemic treatment at our institution were reviewed as a surrogate clinical trial population. A list of priori events was developed to capture the potential for prior cancer to negatively affect clinical trial conduct or endpoints. The proportions of patients that developed an outcome were assessed.ResultsAmong trials registered on clinicaltrials.gov, 66% listed prior cancer in the eligibility criteria, and of these 35% excluded patients with prior cancer in the last 5 years. Of NSCLC patients treated with systemic therapy at Princess Margaret Cancer Center, 20% had prior cancer, of these, breast (20%) and prostate (19%) were the most common malignancies. Median time between prior cancer and NSCLC was 82 months. Median survival was 20 months. For patients without evidence of active prior cancer at baseline, and not on active therapy for prior cancer, no patients had evidence of a recurrence of prior cancer during the treatment and follow‐up for the NSCLC, nor died from prior cancer. However, two patients developed new primaries.ConclusionsA history of prior cancer has a low likelihood of impacting clinical trial endpoints in patients with incurable NSCLC, if not active or requiring treatment. These findings should be validated in larger data sets.

Increasing representation and diversity in cardiovascular clinical trial populations.

Increasing representation and diversity in cardiovascular clinical trial populations.

PCN192 Psychometric Validation of the EORTC QLQ-HCC18 in Patients with Previously Treated Unresectable Hepatocellular Carcinoma

To evaluate the measurement properties of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-question module (EORTC QLQ-HCC18) within a previously treated, unresectable HCC clinical trial population that was distinct from the published QLQ-HCC18 validation populations.

Enrollment disparities in cancer clinical trials leading to FDA approvals between 2008 and 2020.

e18501 Background: Cancer clinical trials based in the United States (US) have lacked adequate representation of racial and ethnic minorities, the elderly, and women. Pivotal clinical trials leading to United States Food and Drug Administration (FDA) approval are often multi-national trials and may also lack generalizability to underrepresented populations in the United States. We determined the racial, ethnic, age, and sex enrollment in pivotal trials relative to the US cancer population. Methods: We reviewed the FDA’s Drug Approvals and Databases for novel and new use drug approvals for breast, colorectal, lung, and prostate cancer indications from 2008 through 2020. Drugs@FDA was searched for drug approval summaries and FDA labels to identify clinical trials used to justify clinical efficacy that led to FDA approval. For eligible trials, enrollment data were obtained from FDA approval summaries, FDA labels, ClinicalTrials.gov, and corresponding journal manuscripts. Enrollment Fraction (EF) was calculated as enrollment in identified clinical trials divided by 2017 SEER cancer prevalence. All data sources were publicly available. Results: From 2008 through 2020, 60 drugs received novel or new use drug approval for breast, colorectal, lung, or prostate cancer indications based on 66 clinical trials with a total enrollment of 36,830. North America accounted for 9,259 (31%) enrollees of the 73% of trials reporting location of enrollment. Racial demographics were reported in 78% of manuscripts, 66% of ClinicalTrials.gov pages, and 98% of FDA labels or approval summaries. Compared with a 0.4% enrollment fraction among White patients, lower enrollment fractions were noted in Hispanic (0.2%, odds ratio [OR] vs White, 0.46; 95% confidence interval [CI], 0.43 to 0.49, P&lt; 0.001) and Black (0.1%, OR 0.29; 95% CI 0.28 to 0.31, P&lt; 0.001) patients. Elderly patients (age ≥ 65 years) were less likely than younger patients to be enrollees (EF 0.3% vs 0.9%, OR 0.27; 95% CI 0.26 to 0.27, P&lt; 0.001) despite accounting for 61.3% of cancer prevalence. For colorectal and lung cancer trials, females were less likely than males (EF 0.7% vs 1.1%, OR 0.66; 95% CI 0.63 to 0.68, P&lt; 0.001) to be enrolled. Conclusions: Black, Hispanic, elderly, and female patients were less likely to enroll in cancer clinical trials leading to FDA approvals from 2008 to 2020. Race and geographic enrollment data were inconsistently reported in journal manuscripts and ClinicalTrials.gov. The lack of appropriate representation of specific patient populations in these key clinical trials limits their generalizability. Future efforts must be made to ensure equitable access, representation, and reporting of enrollees that adequately represent the US population of patients with cancer.

Real-world outcomes in older adults treated with immunotherapy: A United Kingdom multicenter series of 2,049 patients.

12026 Background: Immune checkpoint inhibitor (ICI) therapy is now commonly used in a range of tumours and settings. Most data relating to outcomes and rates of immune-related adverse events (irAE) is derived from clinical trial or registry populations and small case series. Limited data exist for patients aged &gt; 75 years. Here we present a multi-centre, real-world analysis of the outcomes and incidence of irAEs in older adults managed within a single comprehensive public health service. We also compare these outcomes to younger patients in the same cohort. Methods: A retrospective analysis of 2049 patients treated with ICIs was undertaken across 12 centres. All patients were managed within the UK National Health Service outside of a trial setting between June 2016 and September 2018. Patients received either ICI monotherapy (MT) or duel combination ICI therapy (CT) for malignant melanoma (MM), non-small cell lung cancer (NSCLC) or renal cell cancer (RCC). Data were collected using a standardised, collection tool. IrAEs ≥ grade 2 or all-grade endocrinopathies were recorded as per the Common Terminology Criteria for Adverse Events (V5) (CTCAE). Statistical analyses were performed using T-tests, Mann-Whitney and Chi-squared. Kaplan-Meier analysis and log-rank test were used for overall survival (OS) analysis. Results: 409 (20%) of patients were aged &gt; 75 years(a), 1413 (69%) aged 50-75(b) and 227 (11.1%) aged &lt; 50(c). There was no difference in sex, ethnicity or PD-L1 status (in the NSCLC cohort) between groups. Older patients were less likely to receive combination therapy (3%(a) v 13%(b) v 34%(c), p &lt; 0.001). There was no difference in median OS across age groups in the cohort as a whole (p = 0.822) or for the individual tumour groups when treated with single agent ICI. Across the total cohort patients aged &gt; 75 had no increased risk of any irAE (35%(a) v 33%(b) v 41%(c),p = 0.074). However there was an increase in irAEs in older patients treated with MT (36%(a) v 26(b) v 25%(c), p = 0.011) However there was no difference in the &gt; 75s with regard to severe (G3/4) toxicity, toxicity type, admission or discontinuation due to toxicity in the aPD-1 group. In the overall cohort younger patients were more likely to develop irAEs and be admitted. Conclusions: Patients aged &gt; 75 years treated with anti-PD1 therapy in the standard of care setting derive similar survival benefit to younger patients. There was no increase in ≥G3 toxicity. Our data support the safety of single agent aPD-1 ICI therapy in older adults and provide reassurance relating to the impact of toxicity.[Table: see text]