Results from an observational study revealed that patients with cancer who also were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were treated with unproven, investigational therapies for the virus — and most of these drugs were administered outside of the scope of formal clinical trials.1 The only exception to this was remdesivir, which was administered to this population by way of a formal trial in 69% (86) of the 2186 individuals who were enrolled.
The investigators characterized “off trial” as any administration of a drug for coronavirus disease 2019 (COVID-19) through the expanded access route (compassionate use) prior to May 1, 2020, or through emergency use authorization (EUA) after May 1, 2020, and stated in the paper that “limits of temporal resolution in the [COVID-19 and Cancer Consortium; CCC19] registry do not allow for distinguishing between these 2 uses.” The data collection period was from March 17, 2020, to June 26, 2020.
In addition, the investigators determined that there was no statistically significant 30-day all-cause mortality benefit from treatment with hydroxychloroquine or high-dose corticosteroids alone or in combination in patients with active cancer. But, they determined that there may be a mortality benefit with remdesivir in this population. Compared with positive controls (of whom many got prior hydroxychloroquine), remdesivir alone was associated with decreased 30-day all-cause mortality (adjusted odds ratio [aOR], 0.41; 95% CI, 0.17-0.99). The analysis also looked at mortality with other anti–COVID-19 medications, including tocilizumab, azithromycin, high-dose corticosteroids, and other undisclosed therapies.
The study served as a follow-up analysis to a prior study by the CCC19, which found that individuals with cancer were at increased risk of COVID-19. But in the larger follow-up cohort, which involved 2186 patients (of whom 865 received some type of treatment for COVID-19), the researchers calculated that the mortality rate due to COVID-19 was higher than they had previously calculated: it was 16% in the newly published study compared with 13% in the prior study of 928 patients.
COVID-19 mortality rates have been found to be more than twice as high in Black, Latinx, and Indigenous cohorts as in White populations.2 Despite this statistic, in the CCC19 study, non-Hispanic Black patients had a decreased likelihood of receiving remdesivir (adjusted odds ratio [aOR] 0.56; 95% CI, 0.31-1.00). And based on data presented in a supplementary chart in the study, a higher proportion of Black patients received remdesivir off trial than did White patients (38% vs 32%, respectively). A higher proportion of Hispanic patients (36%) compared with White patients got access to remdesivir outside of formal trials as well. Dr Warner cautioned, however, against drawing any conclusions from what are “pretty small numbers overall for the patients receiving [remdesivir] off trial.”
Patients with renal comorbidities (aOR, 0.32; 95% CI, 0.16-0.61) and those with an Eastern Cooperative Oncology Group performance status of 2 or higher (aOR, 0.47; 95% CI, 0.24-0.90) were less likely to receive remdesivir, while those living in the US West were more likely to receive remdesivir (aOR, 1.85; 95% CI, 1.09-3.15).
Considering that Black patients are also more likely to experience severe disease, it would be rational to deduce that this population may potentially be better candidates for the receipt of remdesivir, as the US Food and Drug Administration EUA for the drug was granted specifically for “treatment of suspected or laboratory confirmed [COVID-19] in adults and pediatric patients hospitalized with severe disease.”3
However, it has also been said by the director of the National Institute of Allergy and Infectious Diseases, Anthony S. Fauci, MD, that remdesivir “has its most favorable effect in hospitalized patients with COVID-19 who have modest pulmonary disease.”4
In this CCC19 study, a higher proportion of Black patients had severe disease compared with White patients, and were more likely to receive any type of treatment overall. Of the 476 non-Hispanic Black patients, 75 (16%) had severe baseline COVID-19, whereas 195 of 1649 (12%) with non-missing race who were not non-Hispanic Black had severe baseline COVID-19, Dr Warner said, and noted that this is a significant difference (unadjusted odds ratio, 1.4; P =.03). But, he added, “it is important to note that some patients with mild or moderate baseline COVID-19 go on to develop severe disease.” (Across the cohort and irrespective of race, baseline COVID-19 severity was mild in 1037 of individuals [47%], moderate in 876 individuals [40%], and severe in 273 individuals [12%]).
“It appears that Black patients were underrepresented in the clinical trials of remdesivir, likely due to reasons other than purely clinical factors,” Dr Warner commented in a press release.5 What’s more, Dr Warner told Cancer Therapy Advisor, “even after adjustment for baseline severity, Black patients were less likely to receive remdesivir.”
While hydroxychloroquine treatment alone was not associated with increased risk of mortality in patients with invasive cancer, hydroxychloroquine plus any other therapy had a statistically significant increased risk of 30-day all-cause mortality compared with positive controls (PSM aOR, 1.99; 95% CI 1.29-3.08; unmatched aOR, 1.93; 95% CI, 1.27-2.94). The authors also noted that the “encouraging findings for corticosteroids in the prospective UK RECOVERY trial were not replicated in this cohort of patients with cancer.”
The study authors acknowledged that limitations of the study included confounding by severity, collider bias, lack of randomization, and potential selection bias because of medication access barriers.
“The unfortunate conclusion is that racial disparities in access to clinical trials continue to exist, and one of our recommendations is that the necessary steps to address such disparities need to be accelerated, especially given that Black patients and other people of color appear to be taking the brunt of the COVID-19 pandemic,” Dr Warner concluded in the press release.5
Prior studies examining off-trial access to remdesivir do not give a full picture of the representation of ethnic minorities in clinical trials testing this investigational COVID-19 therapy. In an analysis of the compassionate use of remdesivir published in the New England Journal of Medicine earlier this year, race and ethnicity data for the 53 included individuals were not reported.6 In that trial, patients were only identified by geographic location.
And in a July 10, 2020, press release, Gilead wrote that among the 229 patients in the phase 3 SIMPLE-Severe trial (ClinicalTrials.gov Identifier: NCT04292899) who were enrolled at trial sites in the United States, the rate of clinical improvement (defined as 2 point or higher score on a 7-point ordinal scale at day 14) was determined to be 84% in African-American patients.6 The patient characteristics of race and ethnicity do not appear to be explicitly disclosed across the entire SIMPLE-Severe cohort of 397 study participants (a difference of 168 patients who were not counted in the subgroup analysis).7
Disclosures: Many of the authors of the Cancer Discovery article disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.
- Rivera DR, Peters S, Panagiotou OA, et al. Utilization of COVID-19 treatments and clinical outcomes among patients with cancer: A COVID-19 and Cancer Consortium (CCC19) cohort study [published online July 22, 2020]. Cancer Discov. doi: 10.1158/2159-8290.CD-20-0941
- The COVID Tracking Project. The COVID Racial Data Tracker. https://covidtracking.com/race. Accessed July 22, 2020.
- US Food and Drug Administration. Fact Sheet for health care providers Emergency Use Authorization (EUA) of Remdesivir (GS-5734™). Accessed July 22, 2020.
- Lane HC, Fauci AS. Research in the context of a pandemic [published online July 17, 2020]. N Engl J Med. doi: 10.1056/NEJMe2024638
- Wilemon, T. Vanderbilt University Medical Center. New CCC19 data offer insights on COVID treatments for people with cancer [press release]. Published July 22, 2020. Accessed July 22, 2020.
- Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med. 2020;382:2327-2336.
- Gilead Sciences, Inc. Gilead presents additional data on investigational antiviral remdesivir for the treatment of COVID-19 [press release]. Published July 10, 2020. Accessed July 22, 2020.
- Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 days in patients with severe Covid-19 [published online May 27, 2020]. N Engl J Med. doi: 10.1056/NEJMoa2015301.
This article originally appeared on Cancer Therapy Advisor