Abstract C26: Ethnic, gender, and age disparities and outcome of phase I clinical trials of biologically targeted anticancer agents
Authors: Owonikoko Taofeek K. , Lewis Colleen , Busari Adeniyi K. , Kim Sungjin , Chen Zhengjia , Lawson David H. , Carthon Bradley C. , El-Rayes Bassel F. , Khuri Fadlo R. , Kauh John , Harvey R. Donald , Ramalingam Suresh S. 
Published: May 2015

Abstract
Background: Age, gender and ethnic-based differences in drug metabolism have been previously reported from large population-based studies. The potential impact of these factors on safety and efficacy outcomes in early phase clinical trials has not been well studied.
Methods: We analyzed data from five investigator-initiated phase I clinical trials of targeted biologic agents in solid malignancies conducted at a single academic cancer center. Ethnic distribution of enrolled patients was compared to the referral population demographics at the city, metro and state level. We also analyzed all toxicity experience, dose limiting toxicity (DLT) and clinical benefit to determine any significant differences based on ethnicity i.e. African American, (AA) vs. Caucasian, age or gender. A multivariate logistic regression model was performed to identify significant predictors of DLT.
Results: Data from 117 eligible patients was employed for this analysis: AA/Caucasians (27/85); male/female (66/51); median duration on study was 88 days. AA patients were younger in age than Caucasian patients (56 vs. 62 years, p=0.004), otherwise were comparable in terms of weight, Body Mass Index, frequency or grade of toxicity, DLT experience and gender distribution. GI toxicity of nausea/vomiting was more frequent in female patients (43% vs. 24%, p=0.03) but no disparity by age, gender or ethnicity with other types of toxicities or DLT experience. Using median duration of time on study as surrogate for treatment efficacy, there was no difference by gender (M/F 89 vs. 88 days, p=0.822) or ethnicity (AA/Caucasian: 113 vs. 91 days, p=0.840) but significant correlation with age (-0.194, p=0.038) and body weight (0.234, p=0.012) was observed. AA patients had worse overall survival 7.4 (95%CI: 5.3-16.1) vs. 11.4 (95%CI: 9.2-26.3) months with a higher risk of death on univariate [1.812 (95%CI: 1.079-3.045), p=0.025] and multivariate [HR: 2.037 (95%CI: 1.182-3.512), p=0.010] analyses. There was a modest increase in the risk of death in older patients [HR: 1.028, (95%CI: 1.000-1.056), p=0.046] a non-significant trend in improved survival for female patients [HR: 0.687 (0.357-1.321), p=0.260].
Conclusions: Age-, gender- and ethnic-based disparities were observed with specific toxicity and survival of phase I clinical trials of anticancer agents. An enrichment strategy for age and ethnic subgroups in phase I trials is warranted to ensure reliable generalization of study findings.
Citation Format: Taofeek K. Owonikoko, Colleen Lewis, Adeniyi K. Busari, Sungjin Kim, Zhengjia Chen, David H. Lawson, Bradley C. Carthon, Bassel F. El-Rayes, Fadlo R. Khuri, John Kauh, R. Donald Harvey, Suresh S. Ramalingam. Ethnic, gender, and age disparities and outcome of phase I clinical trials of biologically targeted anticancer agents. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C26. doi:10.1158/1538-7755.DISP13-C26