Hydroxychloroquine regimens for COVID-19 linked to mortality risk for patients with cancer
Hydroxychloroquine in combination with other treatments for COVID-19 appeared associated with increased mortality among patients with cancer, study results showed.
“We conducted this study to more deeply explore a preliminary finding regarding an association of hydroxychloroquine plus azithromycin with increased mortality. With nearly triple the number of patients in the COVID-19 and Cancer Consortium registry, we were able to conduct a more in-depth statistical analysis,” Jeremy L. Warner MD, MS, FAMIA, FASCO, associate professor of medicine and biomedical informatics at Vanderbilt-Ingram Cancer Center, told Healio. “Although the magnitude of the effect was not as large as previously observed, we still found an association of hydroxychloroquine plus other COVID-19 treatments with increased mortality, including after adjustment for baseline COVID-19 severity, which addressed one of the major confounders.”
The COVID-19 and Cancer Consortium (CCC19), which includes more than 100 cancer centers and other organizations, aims to rapidly collect and disseminate prospective, granular, uniformly organized data on patients with cancer who have been diagnosed with COVID-19.
A previous study of CCC19 data showed a 30-day all-cause mortality rate of 13% among patients with active or prior cancer and confirmed COVID-19 infection. Factors associated with increased mortality included receipt of combination treatment with hydroxychloroquine plus azithromycin, older age, male sex, past smoking history, ECOG performance status of 2 or higher, and active cancer status.
The current follow-up study included 2,186 adults (median age, 67 years; interquartile range, 57-77; 51% women; 51% white). Among them, 51% were in remission from cancer, 28% had cancer that was stable or responding to treatment, and 11% had actively progressing cancer. Participants had been diagnosed with severe (12%), moderate (40%) or mild (47%) COVID-19 infection at baseline.
Most patients (81%) presented with solid tumors. The most common malignancy in the cohort was breast cancer (21%).
Forty percent of patients (n = 865) reported treatment with therapies that included hydroxychloroquine plus azithromycin (23%), hydroxychloroquine alone (21%), azithromycin alone (18%), remdesivir (Veklury, Gilead Sciences) alone (7%), hydroxychloroquine plus azithromycin and high-dose corticosteroids (3%), high-dose corticosteroids alone (2%), hydroxychloroquine plus tocilizumab (Actemra, Genentech; 2%), and hydroxychloroquine plus azithromycin and tocilizumab (2%). The other 60% (n = 1,321) received no treatment.
Investigators aimed to identify factors associated with receiving COVID-19 treatment and to examine the potential impact on 30-day mortality after adjusting for baseline factors.
Researchers reported a 30-day all-cause mortality rate of 15%.
Hydroxychloroquine combined with any other treatment appeared significantly associated with increased risk for 30-day all-cause mortality (propensity score-matched adjusted OR [aOR] = 1.99; 95% CI, 1.29-3.08; unmatched aOR = 1.93; 95% CI, 1.27-2.94). Conversely, hydroxychloroquine alone did not appear to increase mortality risk (propensity score-matched aOR = 1.03; 95% CI, 0.62-1.73; unmatched aOR = 0.98; 95% CI, 0.59-1.62).
Remdesivir reduced mortality compared with untreated controls numerically, but the decrease did not reach statistical significance.
Factors associated with the lowest likelihood for receipt of remdesivir included Black race (aOR = 0.56; 95% CI, 0.31-1), renal comorbidities (aOR = 0.32; 95% CI, 0.16-0.61) and ECOG performance status of 2 or higher (aOR = 0.47; 95% CI, 0.24-0.9).
“These findings are now corroborated by multiple prospective trials failing to show a benefit to hydroxychloroquine, which should no longer be used to treat COVID-19. Conversely, we found an encouraging signal for remdesivir, although not quite reaching statistical significance,” Warner told Healio. “We also did not find a benefit for steroids in patients with cancer, which is a different finding than the UK RECOVERY trial, which unfortunately did not explicitly gather cancer as a comorbidity. These discordant findings would make me hesitant to recommend high-dose steroids as COVID-19 treatment in the cancer population until more data are available.”
Future research should aim to identify the role of COVID-19 treatment sequencing, Warner added.
“CCC19 does not collect data to this level of granularity at this time,” he said. “We would also like to better understand the timing of COVID-19 treatment adoption, such as the widespread uptake of hydroxychloroquine between February and May and the more recent uptake of dexamethasone.”
For more information:
Jeremy L. Warner MD, MS, FAMIA, FASCO, can be reached at Vanderbilt-Ingram Cancer Center, 2220 Pierce Ave., 777 PRB, Nashville, TN 37232; email: firstname.lastname@example.org.