Clinical trials as a path toward equity

Abstract

The more things change, the more they remain the same: a cliche for sure; however, the specter of disparity and implications for health care delivery in the United States is on repeat. The paucity of justice, equity, and equality has been no more obvious than during our ongoing coronavirus 2019 (COVID19) pandemic, as observed by many. Racial and ethnic disparities and their effects on the delivery of health care, in particular cancer survival, have long been described. These inequities have been prevalent across the entire spectrum of cancer care, including prevention, early detection (screening), treatment, and survivorship care. Disparities in gastrointestinal cancer risk and outcomes have been no exception. For example, California Cancer Registry data that included 161,820 patients who had colorectal cancer diagnosed between 2000 and 2013 indicated that cancerspecific mortality was significantly higher in Black men and women (36% and 34%, respectively) compared with nonHispanic White patients, although adjustment for all covariables reduced the differences in women. Stage at diagnosis was a significant factor explaining overall survival (OS) disparities. A National Cancer Database assessment of over 600.000 patients who had gastrointestinal cancers, including 62% with colon and rectal cancers, reported undertreatment of Black patients compared with White patients, represented by disproportionally low operative rates in Black patients and decreased survival. African Americans also have the highest incidence of colorectal cancer among all US racial/ethnic groups, with a significant rate of rise for young Blacks. In this issue of Cancer, Snyder et al have assessed whether there were racial differences between Black and White patients who participated in the firstline therapy metastatic colorectal trial Cancer and Leukemia Group B (CALGB)/ SWOG 80405 (ClinicalTrials.gov identifier NCT00265850), including OS, progressionfree survival (PFS), and response to therapy as the primary objectives. The trial compared the benefit of adding either cetuximab or bevacizumab to 5fluorouracil, oxaliplatin, and leucovorin (FOLFOX) or 5fluorouracil,irinotecan, and leucovorin (FOLFIRI) chemotherapy. This study is 1 of the most modern large, randomized trials for patients with metastatic colorectal cancer to date and as such represents the standard of care for patients with this disease. As the authors report, Black patients with colorectal cancer have significantly higher incidence and mortality compared with White patients. Although mortality is decreasing in both Black and White individuals, the decline is principally seen in White patients. As referenced by the authors, previously published clinical trials have reported contradictory observations among trials that have analyzed differences between Black and White patients in the adjuvant setting, although overall it did appear that Black individuals had inferior outcomes compared with Whites. Limited data in the advanced disease setting (NCCTG N9741) showed no racial differences in the time to progression or OS. CALGB/SWOG 80405 enrolled a total of 2334 patients, of whom 12% selfidentified as Black and 81.5% selfidentified as White. The final data set in this secondary analysis included 392 matched pairs of patients. Median OS and PFS did not significantly differ by race. In addition, there was no difference in response to therapy by race. Most toxicities did not differ by race, although Black patients had lower rates and lower odds of experiencing grade ≥3 fatigue. Those who underwent curative surgical resection for metastatic disease after initial chemotherapy were also similar in numbers. Increasingly, KRAS mutation status is recognized as a prognostic factor, and CALGB/SWOG 80405 similarly has demonstrated that patients with KRAS mutations have a lower survival probability than those with KRAS wildtype tumors. The study also noted no racial differences when patients were matched by KRAS status. The authors describe several limitations to their study as a secondary analysis of a propensitymatched cohort of patients. There were differences between the Black and White patients in performance status and palliative intention of treatment (vs neoadjuvant). They note a 3month difference in the median overall survivorship between Black and White patients (26 vs 29 months, respectively); however, this did not reach significance, possibly because the study was underpowered to detect differences