Narjust Duma

Representation of minorities and women in oncology clinical trials: Review of the past 14 years

PURPOSEnMany cancer clinical trials lack appropriate representation of specific patient populations, limiting their generalizability. Therefore, we determined the representation of ethnic minorities and women in cancer clinical trials.nnnMETHODSnEnrollment data from all therapeutic trials reported as completed in ClinicalTrials.gov from 2003 to 2016 were analyzed. We calculated enrollment fractions (EFs) for each group, defined as the number of enrollees divided by the 2013 Surveillance, Epidemiology, and End Results (SEER) database cancer prevalence.nnnRESULTSnOf 1,012 clinical trials, 310 (31%) reported ethnicity with a total of 55,689 enrollees. Participation varied significantly across ethnic groups. Non-Hispanic whites were more likely to be enrolled in clinical trials (EF, 1.2%) than African Americans (EF, 0.7%; P < .001) and Hispanics (EF, 0.4%; P < .001). A decrease in African American (6% v 9.2%) and Hispanic (2.6% v 3.1%) enrollment was observed when compared with historical data from 1996 to 2002. Younger patients (age younger than 65 years) were more likely to be enrolled in clinical trials than the elderly (64% v 36%; P < .001). Low recruitment of female patients was observed in clinical trials for melanoma (35%), lung cancer (39%), and pancreatic cancer (40%).nnnCONCLUSIONnWe observed a decrease in recruitment of minorities over the past 14 years compared with historical data. African Americans, Hispanics, and women were less likely to be enrolled in cancer clinical trials. Future trials should take extra measures to recruit participants that adequately represent the US cancer population.

Representation of Minorities and Elderly Patients in Multiple Myeloma Clinical Trials

Multiple myeloma (MM) occurs in all races, but the incidence in non-Hispanic black patients (NHBs) is two to three times higher than in non-Hispanic white patients (NHWs). We determined the representation of minorities and elderly patients in MM clinical trials. Enrollment data from all therapeutic trials reported in ClinicalTrials.gov from 2000 to 2016 were analyzed. Enrollment fraction (EF) was defined as the number of trial enrollees divided by the 2014 MM prevalence. Participation in MM clinical trials varied significantly across racial and ethnic groups; NHWs were more likely to be enrolled in clinical trials (EF 0.18%) than NHBs (EF 0.06%, pu2009<u2009.0001) and Hispanic patients (EF 0.04%, pu2009<u2009.0001). The median age of trial participants was 62 years, with 7,956 participants (66%) being less than 65 years of age. Collaborations between investigators, sponsors, and the community are necessary to increase access to clinical trials to our minority and elderly patients.

Special Issues in Young Women with Triple-Negative Breast Cancer

Young patients with triple-negative breast cancer tend to present with aggressive, advanced disease at diagnosis. Young patients with breast cancer can face unique challenges, including delays in diagnosis, higher rates of germline mutations, diminished fertility, and other treatment-associated long-term toxicities. All these issues must be addressed as part of their oncology care to ensure the best health and psychosocial outcomes after treatment. In this chapter, we discuss the distinctive issues faced by young women with triple-negative breast cancer.

Hemolytic Uremic Syndrome Associated With Escherichia coli O157 Infection in an Allogenic Stem Cell Transplant Recipient

We report the development of a Shiga toxin–producing Escherichia coli O157 gastrointestinal infection associated with hemolytic uremic syndrome in an allogenic stem cell transplant recipient with a history of gastrointestinal graft-vs-host disease receiving long-term immunosuppression.

Adherence to Guidelines for Breast Surveillance in Breast Cancer Survivors

Background: Guidelines recommend annual mammography after curative-intent treatment for breast cancer. The goal of this study was to assess contemporary patterns of breast imaging after breast cancer treatment. Methods: Administrative claims data were used to identify privately insured and Medicare Advantage beneficiaries with nonmetastatic breast cancer who had residual breast tissue (not bilateral mastectomy) after breast surgery between January 2005 and May 2015. We calculated the proportion of patients who had a mammogram, MRI, both, or neither during each of 5 subsequent 13-month periods. Multinomial logistic regression was used to assess associations between patient characteristics, healthcare use, and breast imaging in the first and fifth years after surgery. Results: A total of 27,212 patients were followed for a median of 2.9 years (interquartile range, 1.8-4.6) after definitive breast cancer surgery. In year 1, 78% were screened using mammography alone, 1% using MRI alone, and 8% using both tests; 13% did not undergo either. By year 5, the proportion of the remaining cohort (n=4,790) who had no breast imaging was 19%. Older age was associated with an increased likelihood of mammography and a decreased likelihood of MRI during the first and fifth years. Black race, mastectomy, chemotherapy, and no MRI at baseline were all associated with a decreased likelihood of both types of imaging. Conclusions: Even in an insured cohort, a substantial proportion of breast cancer survivors do not undergo annual surveillance breast imaging, particularly as time passes. Understanding factors associated with imaging in cancer survivors may help improve adherence to survivorship care guidelines.

Exclusion of Male Patients in Breast Cancer Clinical Trials

Men make up an estimated 1% of patients diagnosed with breast cancer in the United States each year (1). This analysis examined the inclusion and representation of men in breast cancer trials between January 1, 2000, and April 31, 2017. On ClinicalTrials.gov, 426 trials were identified and evaluated for inclusion and recruitment of male breast cancer patients. Of these, 277 trials (65%) excluded male breast cancer patients in their enrollment criteria. Overall, 0.42% of trial participants were men, with the lowest enrollment rates in hormonal and targeted therapy trials (0.1% and 0.1%, respectively). No men were included in the 70 trials studying neoadjuvant therapies. Future trials should take extra measures to recruit male participants to adequately understand the efficacy and safety of new regimens in this subset of patients. In 2018, 2550 new cases of invasive breast cancer will be diagnosed in men (1). Recent studies have identified differences in clinical and biological features between male and female breast cancer, highlighting the importance of inclusion of both sexes in clinical trials (2).The goal of our analysis was to methodically define the representation of men in breast cancer trials. ClinicalTrials.gov was queried on May 1, 2017, for all therapeutic breast cancer trials from January 1, 2000, to April 31, 2017. Search terms included breast cancer and studies with results and interventional trials (n 1⁄4 721 trials). Trials with unknown recruitment status or without status verification in 12 months were excluded. As the registry does not include personal identifiers, this analysis received a waiver for the informed consent requirement. For the analysis, exclusion of male patients was classified as “strict exclusion” vs “allowed” and treated as a binary variable. We used logistic regression models to test the association between male patients’ exclusion and trial characteristics. All statistical tests were two-tailed, and a P value of less than .05 was considered statistically significant. Data analysis was performed using SPSS statistical software. Our initial search yielded 721 trials, 295 of which were later excluded (Figure 1). In the final analysis, 426 trials were included. Only five studies designed to include men were completed; two of these were observational studies (NCT00773669 and NCT00666731). To our knowledge, none of these studies have been peer-reviewed and published in manuscript form (3,4). Table 1 summarizes trial characteristics. During the study period, 31 clinical trials in male breast cancer were early terminated and 11 were withdrawn; none of these were included in our analysis. A total of 106 353 patients were enrolled. Out of 426 breast cancer trials, 277 trials (65%) excluded male breast cancer patients and 28 trials (7%) did not address male patients’ inclusion/exclusion in their criteria. Men represented 0.42% of the trial participants (n 1⁄4 452). Hormonal and targeted therapy trials had the lowest male enrollment rates (0.1% and 0.1%, respectively). Despite chemotherapy trials having the highest proportion of male enrollment (0.2%), the number of male participants was only 234 (Table 1). Further, 70 trials (16%) studied neoadjuvant therapies, and no men were recruited into any of these trials. After dividing trials by phase, 67% of phase I trials included male patients compared with 22% of phase III trials. In univariate analyses, hormonal trials and trials designed for metastatic disease had higher odds of excluding men (odds ratio [OR] 1⁄4 4.17, 95% CI 1⁄4 1.14 to 15.23, P < .03; OR 1⁄4 2.28, 95% CI 1⁄4 1.08 to 4.81, P < .03, respectively). University cooperative group–sponsored trials had lower odds of excluding men than those sponsored by the pharmaceutical industry and National Cancer Institute (NCI)–sponsored trials (OR 1⁄4 0.55, 95% CI 1⁄4 0.27 to 0.98, P < .05). However, none of these associations remained statistically significant in multivariable analysis. Most of the trials included in our analysis were completed between 2011 and 2016 (83%). No changes were seen in the representation of male breast cancer patients over time. Multiple efforts have been spearheaded by the NCI and other institutions to improve the recruitment of men in breast cancer trials. Despite these efforts, we observed that the recruitment of

Commentary: Race and Ethnicity in Biomedical Research – Classifications, Challenges, and Future Directions

The use of race and ethnicity in biomedical research has been a subject of debate for the past three decades. Initially the two major race categories were: White and Black, leaving other minorities uncounted or inappropriately misclassified. As the science of health disparities evolves, more sophisticated and detailed information has been added to large databases. Despite the addition of new racial classifications, including multi-racial denominations, the quality of the data is limited to the data collection process and other social misconceptions.xa0Although race is viewed as an imposed or ascribed status, ethnicity is an achieved status, making it a more challenging variable to include in biomedical research. Ambiguity between race and ethnicity often exists, ultimately affecting the value of both variables. To better understand specific health outcomes or disparities of groups, it is necessary to collect subgroup-specific data. Cultural perceptions and practices, health experiences, and susceptibility to disease vary greatly among broad racial-ethnic groups and requires the collection of nuanced data to understand. Here, we provide an overview of the classification of race and ethnicity in the United States over time, the existing challenges in using race and ethnicity in biomedical research and future research directions.

Where Do We Stand on the Integration of PARP Inhibitors for the Treatment of Breast Cancer

Purpose of ReviewTo provide an overview of the clinical development of poly(ADP-ribose) polymerase inhibitors (PARPi) in breast cancer to date and to review existing challenges and future research directions.Recent FindingsWe summarize the clinical development of PARPi in breast cancer from bench to bedside, and discuss the results of recent phase 3 trials in patients with metastatic breast cancer (MBC) and germline mutations in BRCA1/2 (gBRCAm). We will also provide an update regarding mechanisms of action and resistance to PARPi, and review clinical trials of PARPi as monotherapy or in combination regimens.SummaryPARPi are a novel treatment approach in persons with gBRCA1/2m-associated MBC. Going forward, the clinical applicability of these compounds outside the gBRCAm setting will be studied in greater detail. The identification of accurate predictive biomarkers of response is a research priority.

Pompe Disease Could Mimic Exam Findings of Amyloidosis: Two Rare Diagnoses Bona Fide

A 70-year-old female presented with a three-year history of evolving macroglossia causing dysphagia and dysarthria, with proximal muscle weakness. Given the classic physical finding of macroglossia, the patient underwent extensive evaluation for amyloidosis which proved to be negative apart from a bone marrow biopsy which stained positive for transthyretin without amino acid sequence abnormality, thus giving wild-type transthyretin amyloidosis. Since the wild-type transthyretin amyloidosis could not entirely explain her clinical presentation and evaluation, further studies were conducted in a sequential manner, thus leading to a diagnosis of Pompe disease explaining her presenting signs and symptoms including her macroglossia. Through this fascinating case, we attempt to highlight the approach for the diagnoses of two rare diseases in a patient by emphasizing the importance of having a broad differential diagnosis when presented with findings which may have been thought as pathognomonic for certain diseases.

Abstract A27: Diversity in multiple myeloma clinical trials

Background: Multiple myeloma (MM) accounts for approximately 1% of all cancers and 10% of hematologic malignancies in the United States (U.S.). MM occurs in all races, but the incidence in African Americans is two to three times higher than in non-Hispanic whites. MM is also slightly more frequent in men than women (1.4:1). Many clinical trials lack appropriate representation of specific patient populations, limiting the generalizability of the evidence obtained. Therefore, we determined the representation of ethnic minorities, the elderly, and women in MM clinical trials. Methods: Enrollment data from all therapeutic trials reported as completed in clinicaltrial.gov from 2000 to 2016 were analyzed. Clinical trials including other hematologic malignancies and with recruitment outside of the U.S. were excluded. Enrollment fraction (EF) was defined as the number of enrollees divided by the 2013 SEER database MM complete prevalence. Chi-square test was used to estimate differences in categorical data. Results: Out of 177 MM clinical trials (CT), 78 (44%) reported ethnicity with a total of 12,055 enrollees. Regarding enrollees9 ethnic composition, 84% were non-Hispanic White (NHW), 8.6% African American (AA), 2.8% Asian, 1.8% Hispanic, and 0.1% Native American/Alaskan Indian. Out of those 78 CT, 52 (66%) were phase II, 15 (19%) phase III, and 11 (14%) phase I. Most of the results were published from 2012 to 2016 (74%). Forty-six (59%) trials were sponsored by industry, 7 (9%) by NCI, and 25 (32%) were investigator initiated. Participation in CT varied significantly across ethnic groups, NHW were more likely to be enrolled in CT (EF of 0.23) than AA (EF of 0.08, p Conclusions: Despite the higher incidence of MM in African Americans and the elderly, the former only represented 8.6% of the study participants and 66% of these were less than 65 years of age; therefore, we are lacking data in the tolerability of these new agents in our aging MM population. We also observed that industry studies were less likely to recruit AA patients. Collaborations between investigators, sponsors, and the community are necessary to increase our minority and elderly patients9 access to clinical trials. Citation Format: Narjust Duma, Miguel Gonzalez Velez, Jesus Vera-Aguilera, Richardo Parrondo, Veronica Mariotti, Jonas Paludo, Yucai Wang, Ronald Go, Alex Adjei. Diversity in multiple myeloma clinical trials [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A27.