A phase II trial of UGT1A1 genotype-guided FOLFIRI plus bevacizumab as first-line therapy for advanced, unresectable colorectal cancer.

BACKGROUND: FOLFIRI is a standard regimen for metastatic colorectal cancer (mCRC). We hypothesized that a pharmacogenomic-directed strategy where more efficient irinotecan metabolizers (UGT1A1 *1/*1 homozygotes and *1/*28 heterozygotes) receive higher-than-standard irinotecan doses would improve progression-free survival (PFS) compared to non-genotype selected historical controls with acceptable toxicity. METHODS: In this phase II multicenter study irinotecan dosing in first-line FOLFIRI and bevacizumab for mCRC was based on UGT1A1 genotype with *1/*1, *1/*28, and *28/*28 patients receiving 310 mg/m2, 260 mg/m2, and 180 mg/m2, respectively. Primary endpoint was PFS. Secondary endpoints were investigator and patient-reported adverse events, and estimation of overall survival (OS). RESULTS: One-hundred patients were enrolled with 91 evaluable for PFS and 83 evaluable for best response. Median PFS was 12.5 months (90% CI 10.9, 15.4), shorter than the anticipated alternative hypothesis of 14 months. PFS by genotype was 12.5 months (90% CI 10.9, 17.4) for *1/*1, 14.6 months (90% CI 11.8, 17.5) for *1/*28, and 6 months (90% CI 2.3, 7.7) for *28/28, respectively. OS was 24.5 months (90% CI 19.1, 30.7) and by genotype was 26.5 (90% CI 19.1, 32.9), 25.9 (90% CI 17.6, 37.7), and 13.4 (90% CI 2.3, 20.5) months for *1/*1, *1/*28, and *28/*28, respectively. G3/4 toxicity was similar between all subgroups, including diarrhea and neutropenia. CONCLUSIONS: A pharmacogenomic-directed irinotecan strategy improved PFS in the *1/*1 and *1/*28 genotypes with higher rates of neutropenia and similar rates of diarrhea compared to expected with standard FOLFIRI dosing. However, improvements in response rate and PFS were modest. This strategy should not change standard practice for mCRC patients in the first-line setting.

Race, geography, and risk of breast cancer treatment delays: A population-based study 2004-2015.

BACKGROUND: Treatment delays affect breast cancer survival and constitute poor-quality care. Black patients experience more treatment delay, but the relationship of geography to these disparities is poorly understood. METHODS: We studied a population-based, retrospective, observational cohort of patients with breast cancer in North Carolina between 2004 and 2017 from the Cancer Information and Population Health Resource, which links cancer registry and sociodemographic data to multipayer insurance claims. We included patients >18 years with Stage I-III breast cancer who received surgery or chemotherapy as their first treatment. Delay was defined as >60 days from diagnosis to first treatment. Counties were aggregated into nine Area Health Education Center regions. Race was dichotomized as Black versus non-Black. RESULTS: Among 32,626 patients, 6190 (19.0%) were Black. Black patients were more likely to experience treatment delay >60 days (15.0% of Black vs. 8.0% of non-Black). Using race-stratified modified Poisson regression, age-adjusted relative risk of delay in the highest risk region was approximately twice that in the lowest risk region among Black (relative risk, 2.1; 95% CI, 1.6-2.6) and non-Black patients (relative risk, 1.9; 95% CI, 1.5-2.3). Adjustment for clinical and sociodemographic features only slightly attenuated interregion differences. The magnitude of the racial gap in treatment delay varied by region, from 0.0% to 9.4%. CONCLUSIONS: Geographic region was significantly associated with risk of treatment delays for both Black and non-Black patients. The magnitude of racial disparities in treatment delay varied markedly between regions. Future studies should consider both high-risk geographic regions and high-risk patient groups for intervention to prevent delays.

Seeking Racial Equity in Hematology and Oncology: a Fellow-Led Educational Series to Promote Reflection and Action.

The USA is experiencing a reckoning with racial injustice and graduate medical education programs are seeking ways to address this important topic in training. Fellows in hematology/oncology at the University of North Carolina recognized this important gap and adapted a curriculum for medical residents on racial equity to a subspecialty audience. Aims were (1) to improve knowledge and awareness about implicit bias and systemic racism and (2) introduce methods to address racial inequities. We used lived experiences and collated materials from scientific literature and lay media to illustrate key points. The course explored the effects of implicit bias on individual, clinical, and health system levels, anchored in Kahneman's two-system theory. Videos, journal articles, and group discussion were employed to appeal to many learning styles. A post-curriculum survey assessed perceptions of racial inequality in medicine and the series' effects using a Likert scale. Twenty-nine participants completed the survey (12 fellows), 71% reported improved awareness of racial inequities, and 61% reported improved comfort level in addressing racial inequities. All participants recognized at least "some" racial inequity in medicine, and over 75% of participants indicated interest in further sessions. Formulation of an educational curriculum by fellows and delivered in a division-wide setting was feasible and well received by participants, filling a key educational gap. We encourage other institutions to take similar steps to highlight issues of systemic racism and move our field in the right direction.

The Ethical Imperative of Equity in Oncology: Lessons Learned From 2020 and a Path Forward.

The COVID-19 pandemic and the simultaneous increased focus on structural racism and racial/ethnic disparities across the United States have shed light on glaring inequities in U.S. health care, both in oncology and more generally. In this article, we describe how, through the lens of fundamental ethical principles, an ethical imperative exists for the oncology community to overcome these inequities in cancer care, research, and the oncology workforce. We first explain why this is an ethical imperative, centering the discussion on lessons learned during 2020. We continue by describing ongoing equity-focused efforts by ASCO and other related professional medical organizations. We end with a call to action-all members of the oncology community have an ethical responsibility to take steps to address inequities in their clinical and academic work-and with guidance to practicing oncologists looking to optimize equity in their research and clinical practice.

Racial/Ethnic Disparity in Treatment for Prostate Cancer: Does Cancer Severity Matter?

OBJECTIVE: To determine if there are variations in the receipt of treatment based on race and disease severity. Treatment variations in men with prostate cancer (PCa) among the various racial groups in the United States exist, which may be a source of potential disparity in outcome. METHODS: Utilizing Surveillance, Epidemiology and End Results 17, we identified 327,636 men diagnosed with PCa from 2004 to 2011. Logistic regression analysis was performed to determine the association of receiving definitive treatment and race in the context of disease severity. RESULTS: African American (AA) and Hispanic men were less likely to receive treatment compared to White men (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.71, 0.75, and OR 0.95, 95% CI 0.92, 0.98, respectively). AA men had significantly lower OR of receiving definitive treatment within each D'Amico risk classification compared to White men, with decreasing odds of treatment for each increase in risk category (low-risk OR 0.81, 95% CI 0.78, 0.85; intermediate-risk OR 0.74, 95% CI 0.71, 0.77; and high-risk OR 0.62, 95% CI 0.58, 0.66). Hispanic men with intermediate-risk (OR 0.89, 95% CI 0.84, 0.94) or high-risk (OR 0.79, 95% CI 0.72, 0.85) disease had lower odds of receiving treatment compared to White men. Asian men had similar or greater odds of receiving treatment compared to White men within any Gleason or D'Amico classification. CONCLUSION: There is a significant disparity in the receipt of treatment for PCa among AA and Hispanic men compared to White men. The variations in receipt of treatment reveal an area of opportunity to develop risk-stratified approaches to treatment regardless of ethnic identity, which may address the poorer PCa-related outcomes in these populations.

Racial/ethnic differences in the relative risk of receipt of specific treatment among men with prostate cancer.

OBJECTIVE: African-American (AA) men have excess mortality from prostate cancer compared with White men, which has remained unchanged over several decades. The purpose of this study is to determine if race/ethnicity is an independent predictor of receipt of any definitive treatment vs. watchful waiting/active surveillance (WW/AS). METHODS AND MATERIALS: Men diagnosed with prostate cancer from 2004 to 2011 were identified from the Surveillance, Epidemiology, and End-Results program. Multinomial logistic regression analysis was performed to determine the relative risk ratio (RRR) of receipt of radical prostatectomy (RP), external beam radiation therapy (RT), brachytherapy, cryotherapy, or combination therapy vs. WW/AS. RESULTS: Compared with White men, AA men were significantly less likely to receive RP (RRR = 0.53, P<0.001), brachytherapy (RRR = 0.72, P<0.001), cryotherapy (RRR = 0.84, P = 0.001), and combination therapy (RRR = 0.70, P<0.001), and more likely to receive RT (RRR = 1.03, P = 0.041) vs. AS/WW. Hispanic men were significantly less likely to receive RP (RRR = 0.84, P<0.001) and brachytherapy (RRR = 0.77, P<0.001), and more likely to receive RT (RRR = 1.08, P<0.001), and cryotherapy (RRR = 1.19, P = 0.005) vs. AS/WW compared with White men. CONCLUSIONS: The disparate risk of receiving definitive treatment among AA and Hispanic men represents a significant public health issue that requires efforts to improve physician education, increase cultural competency, and ensure equitable access.