Enrollment Of Patients In Trials Research Articles

Geriatric enrollment patterns in clinical trials at a National Cancer Institute.

e13762 Background: Despite the majority of new cancer diagnoses occurring within the geriatric population, there is a disproportionate rate of clinical trial enrollment within this population. Previous data has estimated enrollment rate to be 18.9% in treatment trials among all adult cancer patients at designated National Cancer Institute Cancer Centers. The objective of this study is to assess geriatric cancer patient clinical trial enrollment rates in a single National Cancer Institute and highlight inequities within cancer care delivery. Methods: We performed a retrospective review of the electronic health record and included patients with cancer ≥ 65 years of age who died at our institution between January 2020 and July 2022. We examined the relationship between cancer type, patient race/ethnic identity, and age and analyzed enrollment in clinical trials. Analyses were conducted using descriptive statistics. Results: Of 117 decedent records analyzed, 11 (9%) were enrolled in treatment clinical trials of which 5 (4.3%) identified as White, 4 (3.4%) Other, and 2 (1.7%) Hispanic. Among the 117 geriatric patient records reviewed, there were 21 Black patients (17.9%) of which 0 (0%) Black patients were enrolled in clinical trials. In comparing enrollment by malignancy type, 5 patients had a hematologic malignancy (leukemia, lymphoma, or multiple myeloma), 3 patients had a genitourinary malignancy, 1 patient had a pancreatic malignancy, 1 patient had an endometrial malignancy, and 1 patient had a breast malignancy. Among all patients analyzed, 37 patients (31.6%) had a hematologic malignancy and 80 patients (68.4%) had a solid tumor malignancy. The average age of enrolled patients was 73, consistent with the average age of all patients analyzed (73.78). Conclusions: Geriatric patients with cancer are disproportionately underrepresented in treatment clinical trials. The inequity is exacerbated when analyzing enrollment among minoritized patients. There was a greater proportion of clinical trial enrollment in patients with hematologic malignancies than solid tumor malignancies, however analysis in larger population samples is necessary. Additional research to identify barriers to clinical trials and methods of increasing geriatric enrollment, including the use of geriatric specific performance scales, is necessary to ensure equitable access and representation in clinical trials. While these results may be skewed in the setting of the COVID-19 pandemic and selection of a decedent population, further research into geriatric accessibility in clinical trials is paramount.

Is physician-patient language discordance a barrier for clinical trial enrollment in patients with cancer? A real-life study.

e18539 Background: Clinical trials are essential for enhancing cancer care. Participation is concerning in racial and ethnic minority groups historically under-represented in research. So, it is crucial to note that, despite Hispanics and African-Americans being 18.9% and 13.6% of the US population, each only represents 4% of the patients enrolled in clinical trials. We address effective doctor-patient communication as a fundamental clinical function in establishing an effective doctor-patient relationship, and is vital in delivering high-quality care. In this study, we question whether physician-patient language concordance affects clinical trial enrollment. Methods: The study evaluated 982 patients diagnosed with cancer who consented to experimental clinical trials in a private practice in Houston, Texas, from 2008-2022. All trials had approved language translations for English and Spanish. We used logistic regression to model the probability of treatment, while adjusting for the effects of cancer type, gender, race, ethnicity, and language (same or different as provider). Results: 982 patients with multiple cancer types (hematological, breast, thoracic/respiratory, genitourinary, gastrointestinal, head and neck and CNS) were included in the study. The most represented tumor types were GI (32%), Breast (24%) and Thoracic (23%). 66% of patients were successfully enrolled in an experimental clinical trial and started treatment, and 95% spoke the same language as their providers. 14% of patients spoke a different language than English, Spanish being the most commonly spoken language other than English spoken by the patient and provider. The study has adequate minority representation (Caucasian 45%, Hispanic 30%, African-American 18% and Asian 5%), and equal gender distribution (52% were female). After evaluating the results, it was found that there was no statistically significant association between physician-patient language and enrollment rates (p = 0.3). It was also found that there was no impact when the assessment was divided by tumor type, gender (p = 0.8) or ethnicity. It also evaluated the rate of consent withdrawal, with only 4% of patients withdrawing consent, showing no statistically significant association with language concordance. Conclusions: In conclusion, our study confirms no significant difference in cancer patients’ enrollment rate in clinical trials if there is language concordance between physician and patient. The efforts of the medical workforce to use translators and translated versions of informed consents, surveys or outcome assessments, when available, seem enough for our patients to collect all the information required to agree to continue enrollment. It is required to further evaluate more variables that impact enrollment in minorities to stop this disparity in cancer care.

Disparities in the Uptake of Telemedicine and Implications for Clinical Trial Enrollment in Patients With Breast Cancer

Purpose/ObjectivesSince the COVID-19 pandemic, telemedicine has emerged as an alternative to office visits in routine radiation oncology practice. The purpose of this study was to identify factors associated with patient preference for an initial consult via telemedicine and correlation with clinical trial enrollment.Materials/MethodsWe evaluated breast cancer patients seen during the open enrollment of a prospective randomized trial from 06/01/2020 to 05/13/2021. Univariate and multivariate logistic regression models were used to identify factors associated with virtual vs in-person initial consultation. All statistical tests were two-sided and the null hypothesis was rejected for p<0.05.ResultsWe identified 476 patient consultations with 259 office visits and 217 telemedicine visits. On multivariate analysis, increased age, unemployment, chemotherapy receipt and radiation at our institution were associated with decreased usage of telemedicine for consultation visit. Out of 217 patients who underwent a telemedicine initial consultation, 10% were eligible to enroll on the trial and of those eligible, 76% enrolled. Out of 259 patients who underwent office visit initial consultation, 14% were eligible to enroll on the trial and of those eligible, 53% enrolled. Among eligible patients, there was no statistically significant difference in clinical trial enrollment between telemedicine and office visits.ConclusionOlder patients, unemployed patients, those receiving chemotherapy and those who subsequently received radiation at our institution were less likely to use telemedicine for their initial consult. Despite these disparities in telemedicine usage, there was no difference in clinical trial enrollment. Telemedicine may be an effective platform for clinical trial enrollment though further strategies to improve its access are essential.

A nationwide analysis of clinical trial participation for common hepato-pancreato-biliary malignancies demonstrates survival advantages for subsets of trial patients but disparities in and infrequency of enrollment.

We describe factors associated with trial enrollment for patients with hepato-pancreato-biliary (HPB) malignancies. We analyzed the association and effect of trial enrollment on overall survival (OS). The National Cancer Database (2004-2017) was queried for common HPB malignancies (pancreatic adenocarcinoma [PDAC] & neuroendocrine tumors, hepatocellular carcinoma [HCC], biliary tract cancers [BTC]). Multivariable logistic regression was used to identify factors associated with trial enrollment. OS was analyzed by multivariable Cox regression. Inverse-probability-weighted Cox regression was utilized to determine the effect of trial enrollment on OS. A total of 1573 (0.3%) of 511,639 patients were enrolled in trials; pancreatic malignancy: 1214 (0.4%); HCC: 217 (0.14%); BTC: 106 (0.15%). HCC and BTC were associated with lower likelihood of enrollment compared with pancreatic malignancy. Black and Hispanic patients were less likely to be enrolled compared to White patients. Treatment at academic facilities and metastatic disease were associated with higher likelihood of enrollment. Enrollment was associated with higher OS for PDAC, metastatic HCC, and metastatic BTC. Trial enrollment exhibited an OS advantage for PDAC and metastatic HCC. Nationally, fewer than 1% of patients with HPB malignancies were enrolled in clinical trials.There are racial, sociodemographic, and facility-based disparities in trial enrollment.

Abstract 1899: TrialMatch: A computational resource for the management of biomarker-based clinical trials at a precision oncology center

Abstract Introduction: The adoption of routine tumor sequencing, and the incorporation of biomarker-based clinical trials in the treatment of cancer has been steadily rising over the past few years. Access and ability to participate in clinical trials is a key element in providing therapeutic options for cancer patients.At the Avera Cancer Institute, options of biomarker-based clinical trials are routinely presented to the treating clinicians at the molecular tumor board (MTB). With everincreasing numbers of trials, a systematic method for keepingtrack of available trials andevaluating patients for trial options was needed. A search for solutions led to only one open-source tool, MatchMiner, but it did not meet our needs. Methods and Results: We developed an open-source web application, TrialMatch, that has the ability to (i) add trials through a semi-automated curation interface, (ii) browse and search trials, (iii) and match patients to biomarker-based trials.TrialMatch is an R Shiny application that uses a mongo database to store the trial data. Software installation and application instantiation is managed through Docker. Curate This section has fields for a user to enter trial name and a NCT ID from clinicaltrials.gov. It then queries the clinicaltrials.gov API and fetches data about the sponsor, treatment, etc.Although disease and biomarker data are available on clinicaltrials.gov, they are not stored as discrete fields that can be queried, and hence require manual input. The user provides disease type based on the OncoTree classification, as well as biomarker information for mutations, copy numbers, fusions, TMB, MSI status, PD-L1 status, RNA expression, and disease specific markers such as ER/PR/HER2 status.All information for a particular trial is entered in a mongo database collection, with each trial stored as a document. The ability to add and edit data fields can be restricted to specific users. Browse This section allows the user to browse through all trials with key information such as NCT ID, trial name, disease, and biomarkers. Each row represents one trial and can be expanded to show more detailed information. This is useful to keep track of trials, and to quickly filter trials to a specific disease or biomarker. Match This section displays a patient-centric view of the trials that each patients’ age, sex, disease, and biomarkers have matched to. The matching can be automated for scheduled recurrentruns. At Avera, this is used during MTB to evaluate treatment options, but can also be used by clinicians to get a sense of the trials available for their patients, while awaiting formal review. Conclusion: We believe that this computational tool fulfills a crucial need in the clinical application of precision oncology, and will ultimately increase clinical trial enrollment for patients. Citation Format: Anu Amallraja, Shivani Kapadia, Padmadpriya Swaminathan, Casey Williams, Tobias Meissner. TrialMatch: A computational resource for the management of biomarker-based clinical trials at a precision oncology center [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 1899.

Abstract PR-05: Worsening disparities of racial minority participation in phase 1 early drug development trials in the United States, 2001-2018

Abstract Purpose: The National Institute of Health has advocated for broad representation of racial and ethnic groups in drug development trials after the introduction of the Revitalization Act in 1993. However, no studies to date have specifically examined demographic disparities among participants in Phase 1 drug development trials. Herein we sought to assess the distribution of and changes in enrollment of racial and ethnic minorities in United States Phase 1 early drug trials for metastatic cancer treatment from 2001 to 2018. Patients and Methods: We queried the ClinicalTrials.gov website to identify completed Phase 1 drug trials in the U.S. from 2001 to 2018 with published results and participants &amp;gt; 18 years of age with metastatic cancer. We reviewed publications from each study to identify racial and ethnic compositions of participants. We compared the proportions of each racial/ethnic group of trial participants to those of corresponding annual incidence data from Surveillance, Epidemiology, and End Results (SEER); for each racial/ethnic group, the difference between trial and SEER proportions was examined using a two-sample test for equality of proportions with continuity correction. Results: We identified a cohort of 236 trials; 72% were industry-sponsored, 19% focused on metastatic breast cancer, 14.8% focused on metastatic colorectal cancer, and 28.3% were basket trials targeting specific genetic pathways with mixed histologies. Of the 9,273 total participants, 81.5% were White, 5.7% Black, 9.4% Asian/Pacific Islander (API), 0.26% American Indian/Alaska Native, and 4.4% Hispanic/Latinx. Comparing the racial/ethnic distributions of trial participants to the corresponding SEER data revealed an excess of White and API representation (1.2% (p&amp;lt;0.005) and 2.3% (p&amp;lt;0.001), respectively), and a 6.2% deficit of Black participants (p&amp;lt;0.001). White patients were overrepresented in clinical trials beginning in 2001-2011 (+4.5% p&amp;lt;0.001)), but not in trials beginning in 2012-2018 (-0.05% p&amp;gt;0.05)). Underrepresentation in trial enrollment worsened in this time period for Black patients (-4.2% to -7.4%, respectively) and Hispanic/Latinx patients (-0.07% to -3.5%). API patients shifted from underrepresentation in 2001-2011 (-2.5%) to overrepresentation in 2012-2018 (+5.52%). Disparities in Black patient enrollment in trials conducted at academic institutions worsened from -4.36% in 2001-2011 to -7.64% in 2012-2018 (p&amp;lt;0.0001). Conclusions: There are persistent and worsening disparities in accrual of racial and ethnic minorities in phase 1 drug trials. These include decreases in enrollment of Black and Hispanic/Latinx patients in clinical trials overall, and in enrollment of Black and AI/AN patients in trials conducted at academic institutions. These findings may represent widening inequalities in access to trial sites, as well as potential systemic biases. Current efforts to diversify clinical trials should expand their reach from phases 2 and 3 to include phase 1, in order to improve equity in access to new treatments at every stage. Citation Format: Hayley M. Dunlop, Evelyn Fitzpatrick, Kevin Kurti, Stephanie Deeb, Erin Gillespie, Fumiko L. Chino, Laura Dover, Cherry Estilo, C. Jillian Tsai. Worsening disparities of racial minority participation in phase 1 early drug development trials in the United States, 2001-2018 [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR-05.

Oncology trial enrollment trends following the first wave of the COVID-19 pandemic.

1565 Background: The first wave of the COVID-19 pandemic was associated with a negative effect on global oncology clinical research and development including documented decreases in new trial launches and patients enrolling on existing trials. We sought to evaluate secular trends in patient enrollment on global oncology trials of drugs and/or biological agents coincident with trends in the pandemic through 10/31/2020. Methods: This time-series study of global oncology clinical trial patient enrollment relied on data from the Medidata Enterprise Data Store, which comprises studies using the RAVE electronic data capture platform, and eCDC. We quantified the number of patients enrolling on oncology trials according to contiguous pandemic waves between 01/05/2020 and fixed right censoring at 10/31/2020. For this study, we defined pandemic waves empirically through review of peaks and nadirs of global case counts/week from eCDC data: wave 1 (01/05/2020-05/02/2020), wave 2 (05/03/2020-08/22/2020), wave 3 (08/23/2020-10/31/2020). We used negative binomial regressions to evaluate associations between time periods (i.e., waves) and counts of new trial enrollees and time periods and counts of new COVID-19 patients. Results: A total of 54,752 patients enrolled in 1,176 oncology trials world-wide during the observation period: 14,888 patients during wave 1, 19,631 patients during wave 2, and 20,233 patients during wave 3 of the pandemic. Compared to wave 1, the incidence of new trial enrollees increased by 10% in wave 2 (incidence rate ratio [IRR] 1.10, 95% confidence interval [CI] 0.95-1.26) and by 29% in wave 3 (IRR 1.29, 95% CI: 1.10-1.52). Over the same period, 47,336,995 people were diagnosed with COVID-19 infection: 3,481,165 patients during wave 1, 20,205,244 patients during wave 2, and 23,650,586 patients during wave 3. Compared to wave 1, the incidence of new COVID-19 patients increased by 617% in wave 2 (IRR 6.17, 95% CI: 2.76-13.77) and by 1,155% (IRR 11.55, 95% CI: 4.61-28.95) in wave 3. Conclusions: Despite substantial increases in the incidence of COVID-19 following the first wave of the pandemic, the number of patients enrolled in oncology clinical trials increased notably during the same period. Future research seeks to understand the mechanism through which the oncology research and development enterprise adapted to the shock of the COVID-19 pandemic. eCDC Source: European Centre for Disease Prevention and Control. Data provided subject to license available at: https://www.ecdc.europa.eu/en/copyright

Barriers to Clinical Trial Enrollment in Patients With Pancreatic Adenocarcinoma Eligible for Early-Phase Clinical Trials.

Early-phase clinical trials are critical to the advancement of cancer care, especially in patients with pancreatic ductal adenocarcinoma, given its aggressive nature and limited available therapeutic options. A retrospective chart review of all patients with refractory or metastatic pancreatic ductal adenocarcinoma, referred to the Sarah Cannon Research Institute at HealthONE between 2014 and 2019, were reviewed. Patients who completed genomic profiling and qualified for a phase 1 trial (primarily 1a but some 1b) were identified to assess barriers to trial enrollment. Of 74 identified patients, 54 patients (73%) qualified for at least 1 clinical trial based on eligibility criteria and alterations detected via molecular profiling. Up to 40 industry-sponsored clinical trials were available during this time for consideration. Of the 54, 28 patients (52%) enrolled in a clinical trial, while 26 (48%) did not enroll. The most frequently cited barriers to enrollment were concerns regarding time commitment (12%), prolonged wait time for enrollment (12%), and fear of adverse events (8%). Seven of the 26 patients (27%) were lost to follow-up or had no stated reason for declining enrollment; others did not go on trial due to death/transition to hospice (n=5; 19%) or progression of disease/declining functional status (n=4; 15%). There were few statistically significant differences between patients who chose to go on trial and those who declined. An understanding of why eligible patients elect not to participate in early-phase clinical trials provides insight into the patient experience and can help identify misperceptions and areas for improvement in education and the clinical trial enrollment process.

Abstract A056: A study of race and socioeconomic status impacting therapeutic clinical trial enrollment in adult gliomas patients

Abstract Introduction: Under-enrollment in clinical trials significantly limits valid analyses of clinical interventions and generalizability of findings. It can also result in premature study termination, with estimates of 22% to 50% of clinical trials being terminated due to poor accrual. Currently, there are limited reports addressing the influence of race, ethnicity and socioeconomic status on clinical trial enrollment in patients with adult glioma. The goal of this study was to determine if race and socioeconomic status impacts clinical trial participation for glioma patients. Methods: A search within the UCSF Tumor Board Registry identified 852 adult patients discussed over a 2-year period. This cohort was analyzed to determine the rate of therapeutic clinical trial consideration, tumor board recommendation, and study enrollment based on clinical reports available through the electronic medical record. Results: At the time of initial diagnosis, 30.7% and 18.0% of glioma patients were recommended and enrolled in a therapeutic clinical trial, respectively. At the time of recurrence, 38.7% and 25.3% of patient were recommended and enrolled in a clinical trial, respectively. Nineteen percent of the study population belonged to a NIH designated underrepresented minority group, with Asian/Pacific Islander patients comprising 10.3% of the total patient cohort. Percentage of patients who enrolled in a clinical trial was comparable between subgroups. On univariate analysis, only in-state location, distance to the hospital, and WHO grade were associated with consideration, recommendation, and enrollment at initial diagnosis and recurrence. Minority status, insurance type, median household income, and percent below poverty line based on county of residence were not associated with clinical trial recommendation or enrollment. Conclusion: Race and socioeconomic status did not impact clinical trial consideration, tumor board recommendation, or study enrollment. Our results do not support the premise that provider decisions are impacted by biases based on minority or socioeconomic status. Citation Format: Sheantel J Reihl, Ramin A Morshed, Sofia Kakaizada, Eric Zhang, Jacob S Young, Jennifer Clarke, Nicholas Butowski, Jennie Taylor, Nancy Ann Bush, Manish K Aghi, Mitchel S Berger, Susan Chang, Shawn L Hervey-Jumper. A study of race and socioeconomic status impacting therapeutic clinical trial enrollment in adult gliomas patients [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A056.

Variety of clinical trial enrollment by actionable tumor suppressor genotype.

e15674 Background: In the last decade, genomics has been increasingly used for therapeutic management of cancer. In precision oncology, genes that can be directly or indirectly targeted with therapeutic agents are considered “actionable”. However, not all alterations affect gene function and alterations in tumor suppressor genes are especially challenging to interpret. The objective of this study was to determine frequency of trial enrollment in patients with “actionable” tumor suppressor alterations and determine whether this varied by genotype and tumor type. Methods: A single-institution retrospective review was performed on patients with metastatic, advanced, or recurrent solid tumors perceived to likely benefit from genomic profiling. Between 1/2015 and 1/2020, the top 5 tumor suppressor alterations CDKN2A, BRCA1/2, PTEN, ATM and NF1 were considered most common “actionable” tumor suppressor genes among patients reviewed by MD Anderson Precision Oncology Decision Support system. Once literature-based or inferred actionability of the tumor-suppressor alteration was determined, a clinical record review was performed to assess an institution-specific annotation detailing trial availability. This annotation matches somatic genomic alteration based on therapeutic significance and availability of matched investigative therapy based on available literature at the time. From here, patient demographics and trial enrollment was extracted from the electronic medical record. Results: 424 patients were categorized as having actionable alterations that had a trial available for enrollment based on genomic characteristics. Of these, 61 patients (14%) enrolled in a matched trial. Primary reasons for non-enrollment for a specific alteration were: enrollment in non-targeted therapeutic trial (39%), treatment with another stand of care therapy (32%), or enrollment in another genomically matched trial targeting another genomic alteration (14%). There was variability in enrollment by disease type approaching statistical significance (p = 0.073). CDKN2A alterations were the most common while BRCA1/2 had the highest rate of matched enrollment (39.5%). Conclusions: In this cohort of patients, the presence of an actionable tumor-suppressor alteration was associated with trial enrollment varying by genotype. Further work is needed to determine the impact of decision support on trial enrollment as well as strategies to increase actionability by building genomically-driven combination therapy trials.

ACTR-35. A STUDY OF RACE AND SOCIOECONOMIC STATUS IMPACTING THERAPEUTIC CLINICAL TRIAL ENROLLMENT IN ADULT GLIOMAS PATIENTS

Abstract OBJECT Under-enrollment in clinical trials significantly limits valid analyses of clinical interventions and generalizability of findings. Often it results in premature study termination, with estimates of 22% to 50% of clinical trials terminated due to poor accrual. Currently, there are limited reports addressing the influence of race/ethnicity and socioeconomic status on clinical trial enrollment in patients with adult glioma. The goal of this study was to determine if these factors impact clinical trial participation for glioma patients. METHODS 852 adult patients were identified from the UCSF Tumor Board Registry and analyzed to determine the rate of therapeutic clinical trial consideration, tumor board recommendation, and study enrollment based on clinical reports in their electronic medical records. RESULTS At initial diagnosis, 30.7% and 18.0% of glioma patients were recommended and enrolled in a therapeutic clinical trial, respectively. At recurrence, 38.7% and 25.3% of patients were recommended and enrolled in a clinical trial, respectively. Nineteen percent of the study population belonged to a NIH-designated underrepresented minority group; Asian/Pacific-Islander comprising 10.3% overall. On univariate analysis, only in-state location, distance to the hospital, and WHO grade were associated with consideration, recommendation, and enrollment at initial diagnosis and recurrence. Minority status, insurance type, median household income, and percent below poverty were not associated with clinical trial recommendation or enrollment. CONCLUSION Race and socioeconomic status did not impact clinical trial consideration, tumor board recommendation, or study enrollment. Our results do not support the premise that provider decisions are impacted by biases based on minority or socioeconomic status.

Exploring racial disparities of actionable mutations in gynecologic cancers.

e17098 Background: Next Generation Sequencing (NGS) guides targeted therapy and clinical trial enrollment for patients with gynecologic malignancies. South Florida is a key region to explore biomarkers and molecular alterations common in Hispanic (H) patients due to the high proportion of H individuals. While NGS testing is increasingly used in clinical practice to aid in treatment planning, ethnic minorities are at risk for health disparity including clinical trial enrollment. The objective of this study was to determine if frequently reported mutations are also common in a predominantly H population with gynecologic cancers. Methods: Clinicopathologic data was obtained from women treated at our institution from Jan. 2014 to Jan 2019 for gynecologic malignancies. Women with ovarian (OC), endometrial (EC), and cervical cancer (CC) with NGS results from Caris Life Sciences were included for analysis. Women self-report ethnicity based on initial hospital intake form. Mutations based on point mutations, indels, fusions and copy number variations were identified. Descriptive statistics are reported. IRB approval was obtained. Results: A total of 233 patients with 117 ovarian (OC), 24 cervical (CC) and 92 endometrial cancers (EC) were included. Among the 233 women, 96 (41%) were H, 137 (59%) identified as NH. There were 38 H and 48 NH patients with EC; 50 H and 62 NH OC patients; and 8 H and 13 NH CC patients. Among EC patients, TP53 appeared in 42% vs. 47%, PTEN 26% vs. 30% , PIK3CA 32% vs. 17%, CTNNB1 32% vs. 17% , and KRAS 16% vs. 21% of H and NH cases respectively. In the OC cohort, TP53 appeared in 74% vs. 75% , BRCA1/2 10% vs. 19%, KRAS 16% vs. 16% and PIK3CA 8% vs. 6% of H and NH cases respectively. In CC patients, TP53 appeared in 25% vs. 23%, KMT2C 12.5% vs. 7.6% and PIK3CA 0 vs. 38% of H and NH cases respectively. There were no statistical differences in the mutation rates between the two groups. Conclusions: There is limited data reported on the variation of mutations based on ethnicity in women with gynecologic cancers. Our study suggests there may be different driver mutations based on ethnicity. Future studies in larger cohorts are needed to further assess genomic differences, potential responses to treatment and further increase H population enrollment into clinical trials.

Cost and effectiveness of genetic testing in metastatic colorectal cancer (mCRC) at Montefiore Medical Center (MMC).

e15043 Background: Upfront testing for MSI, and mutations in KRAS, NRAS, and BRAF is recommended. The most cost-effective way of obtaining this information remains unclear. We examined cost of broad next generation sequencing (NGS), in comparison to hotspot (HT) and individual target (IT) testing in patients with mCRC with Medicare (MC) and commercial insurance (CI) at MMC. As a surrogate of effectiveness, we hypothesize that patients with NGS are more likely to enroll in clinical trials. Methods: Cost of individual and hotspot tests were derived from known reimbursement rates with insurances affiliated with MMC. Due to ongoing changes in current procedural terminology for NGS, we used known reimbursement amounts from our patients. We applied these costs to a model population of 1,000,000 people. We then evaluated clinical trial enrollment of patients who had either NGS or hotspot/individual testing. Results: MC costs for IT, HT, NGS testing were $1,504, $752, and $4,680 respectively. CI costs were $1,910, $814, $2,366 for IT, HT, and NGS testing respectively. When applied to our model population, NGS cost $914,604 and $1,131,016 more than individual and hot spot testing respectively for MC patients, and $21,432 and $72,924 more for CI patients. Analysis of effectiveness included 136 patients, wherein 8% of those with NGS (n = 5/61) were enrolled in clinical trials as a result of testing compared to 1% of those with HT/IT (n = 1/75). Conclusions: Broad spectrum NGS costs more than individual or hot spot testing in mCRC. However, patients with NGS testing were more likely to be enrolled in clinical trials, suggesting the need for studies to further evaluate ideal testing modality. [Table: see text]

Clinical trial enrollment in patients with endocrine neoplasm: Parity achievable, but cancer type-specific

BackgroundWe sought to assess participation of underrepresented minorities with endocrine neoplasms in clinical trials conducted in the National Cancer Institute's (NCI) Intramural Research Program. MethodsWe performed a retrospective analysis of patients enrolled in Endocrine Oncology Branch (EOB) clinical trials, comparing demographics to regional and national demographics. We compared specific endocrine cancer patient data to data from NCI's Surveillance, Epidemiology, and End Results (SEER) program. ResultsComparing EOB patients to national demographics, we found more white (77% vs 74%, P < 0.001) and black patients (14% vs 12%, P < 0.001). For thyroid cancer, there were more black (16% vs 7%, P < 0.0001) and other minority patients (17% vs 11%, P < 0.0001) compared to SEER. For gastroenteropancreatic neuroendocrine tumors (GEPNETs), there were fewer black (6% vs 19%, P < 0.0001) and other minority patients (6% vs 8%, P < 0.0001). ConclusionEnrollment parity of underrepresented minorities into clinical trials is achievable, although possibly cancer type-specific.

Cost and effectiveness of genetic testing in metastatic colorectal cancer (mCRC) at Montefiore Medical Center (MMC).

643 Background: Upfront testing for MSI, and mutations in KRAS, NRAS, and BRAF is recommended. The most cost-effective way of obtaining this information remains unclear. We examined cost of broad next generation sequencing (NGS), in comparison to hotspot (HT) and individual target (IT) testing in patients with mCRC with Medicare (MC) and commercial insurance (CI) at MMC. As a surrogate of effectiveness, we hypothesize that patients with NGS are more likely to enroll in clinical trials. Methods: Cost of individual and hotspot tests were derived from known reimbursement rates with insurances affiliated with MMC. Due to ongoing changes in current procedural terminology for NGS, we used known reimbursement amounts from our patients. We applied these costs to a model population of 1,000,000 people. We then evaluated clinical trial enrollment of patients who had either NGS or hotspot/individual testing. Results: MC costs for IT, HT, NGS testing were $1,504, $752, and $4,680 respectively. CI costs were $1,910, $814, $2,366 for IT, HT, and NGS testing respectively. When applied to our model population, NGS cost $914,604 and $1,131,016 more than individual and hot spot testing respectively for MC patients, and $21,432 and $72,924 more for CI patients. Analysis of effectiveness included 136 patients, wherein 8% of those with NGS (n = 5/61) were enrolled in clinical trials as a result of testing compared to 1% of those with HT/IT (n = 1/75). Conclusions: Broad spectrum NGS costs more than individual or hot spot testing in mCRC. However, patients with NGS testing were more likely to be enrolled in clinical trials, suggesting the need for studies to further evaluate ideal testing modality. [Table: see text]

1636P - Perceptions of clinical trial enrollment in patients with bone and soft tissue sarcoma

1636P - Perceptions of clinical trial enrollment in patients with bone and soft tissue sarcoma

Genomic characterization of primary and metastatic prostate cancer (PC) using a targeted next-generation sequencing assay.

254 Background: Genomic alterations in PC have been described across the disease continuum, creating opportunities for selective clinical trial enrollment of patients (pts) with high-risk or metastatic disease based on their tumor profile. MSK-IMPACT is an exon capture-based sequencing assay performed in a CLIA-certified laboratory that targets 410 cancer-associated genes, many of which are potential drug targets. We assessed mutations and copy number alterations (CNAs) in primary and metastatic samples from untreated, hormone-treated and castration resistant pts. Methods: PC pts were enrolled on an IRB-approved protocol for tumor genomic profiling. Fixed tumor and matched germline samples were subjected to DNA sequencing analysis using MSK-IMPACT for the identification of somatic mutations and CNAs. Results: 315 samples from 271 pts were successfully sequenced (Table). Overall success rate was 80% (67% for bone). 14 tumors were pathologically classified as neuroendocrine or had neuroendocrine features. 23% of patients had tumor somatic alterations in DNA repair genes (BRCA2, BRCA1, ATM, FANCA and CDK12). Additional alterations were observed in PI3K, MAPK and Wnt-βCatenin pathway genes. Common alterations in the metastatic tumors include TP53 deletion/mutation (42%), AR amplification/mutation (38%), PTEN deletion/mutation (27%), RB1 deletion/mutation (20%), BRCA2 deletion/mutation (11%), FOXA1 mutation (11%) and SPOP mutation (4%). Among metastatic samples, tumors from pts with castration-resistant disease had higher CNA burden when compared to tumors from non-castration-resistant pts (0.31 vs. 0.19 fraction genome altered, p &lt; 0.05, unpaired t-test), as well as higher rates of AR amplification/mutation (49% vs. 3%, p &lt; 0.01, Fisher’s exact test). Conclusions: Genomic profiling of primary and metastatic prostate tumors is feasible with the clinical MSK-IMPACT sequencing assay and has identified actionable alterations in &gt; 40% of patients. This is allowing for selective trial enrollment and further investigation of PC genomics. [Table: see text]

Mocetinostat (MGCD0103): a review of an isotype-specific histone deacetylase inhibitor

Introduction: HDAC inhibitors (HDACIs) have the potential to restore gene expression and display antitumor effects in vitro. As single agents, HDACIs have clinical activity in lymphoma. In myeloid leukemias, combinations of DNA methylation inhibitors and HDACIs are promising. Other combinations are being studied in solid tumors.Areas covered: This article covers basic information and an update on preclinical and clinical experience with the oral isotype-selective HDACI MGCD0103 (mocetinostat) in hematological malignancies and solid tumors. It also examines data concerning MGCD0103 from recent conferences and articles through to November 2010, including new data regarding responses in lymphoma and toxicities.Expert opinion: MGCD0103 is well-tolerated and exhibits favorable pharmacokinetic and pharmacodynamic profiles, demonstrating target inhibition and clinical responses. It induces cell death and autophagy, synergizes with proteasomal inhibitors and affects non-histone targets, such as microtubules. In 2008, new patient enrollment in trials was temporarily suspended due to potential cardiac complications. This restriction was lifted in 2009 as no correlation between MGCD0103 exposure and pericardial effusions was found. New patient enrollment in MGCD0103 clinical trials requires the exclusion of patients diagnosed with significant cardiac abnormalities prior to enrollment. Clinical and pharmacodynamic data support a three-times-weekly administration at a 90 mg fixed dose. MGCD0103 displays promising antitumor activity in several hematological diseases.

Should persons with autosomal dominant AD be included in clinical trials?

In a recent issue of Alzheimer’s Research & Th erapy, we read with great interest the discussion by Szigeti and Doody [1] of including early-onset Alzheimer’s disease (EOAD) (under age 65) in clinical trials. Successful enroll ment is a challenge in most Alzheimer’s disease (AD) trials, and permitting the participation of these young motivated patients could aid recruitment. EOAD can be categorized as AD caused by autosomal dominant mutations (ADAD) in the amyloid precursor protein (APP), presenilin-1 (PSEN1), or presenilin-2 (PSEN2) genes and as AD in individuals not known or suspected to harbor such mutations, which we here refer to as sporadic AD (SAD). We agree with the authors that SAD cases under age 65 should be included in AD trials. Th e literature describing these cases does not suggest that clinical or biological diff erences warrant exclusion. We take pause, however, with the recommendation of categorical enrollment of ADAD patients in trials. Inclusion of persons with ADAD should be dependent upon the nature of the causative mutation, the drug under investigation, and the study objectives. More than 200 AD-causing mutations are known, and predicting the impact of all disease-causing

Standardization of surgical and pathologic variables is needed in multicenter trials of adjuvant therapy for pancreatic cancer: results from the ACOSOG Z5031 trial.

Standardization of surgical and pathologic techniques is crucial to the interpretation of studies evaluating adjuvant therapies for pancreatic cancer (PC). To assess the degree to which treatment administered prior to enrollment of patients in trials of adjuvant therapy is quality controlled, the operative and pathology reports of patients in American College of Surgeons Oncology Group (ACOSOG) Z5031-a national trial of chemoradiation following pancreaticoduodenectomy (PD)-were rigorously evaluated. We analyzed variables with the potential to influence staging or outcome. 80 patients reported to have undergone R0 (75%) or R1 (25%) pylorus-preserving (38%) or standard (62%) PD were evaluated. A search for metastases was documented in 96% of cases. The proximity of the tumor to the superior mesenteric vein was reported in 69%; vein resection was required in 9% and lateral venorrhaphy in 14%. The method of dissection along the superior mesenteric artery (SMA) was described in 68%, being ultrasonic dissection (17%), stapler (24%), and clamp and cut (59%). SMA skeletonization was described in 25%, and absence of disease following resection was documented in 24%. The surgeon reported marking the critical SMA margin in 25%; inking was documented in 65% of cases and evaluation of the SMA margin was reported in 47%. A range of 1-49 lymph nodes was evaluated. Only 34% of pathology reports met College of American Pathologists criteria. Trials of adjuvant therapy following PD suffer from a lack of standardization and quality control prior to patient enrollment. These data suggest areas for improvement in the design of multidisciplinary treatment protocols.