Disease Progression, Hydroxychloroquine and Azithromycin Treatment Linked to Increased Risk of Death in Patients With Cancer and COVID-19

Disease progression in patients with cancer and COVID-19 was associated with an increased risk of death compared to patients who were either in remission or had no evidence of cancer, according to data from the COVID-19 and Cancer Consortium registry presented during a 2020 ASCO Virtual Scientific Program press briefing.

Additionally, the analysis demonstrated that hydroxychloroquine and azithromycin treatment for COVID-19 was also strongly associated with an increased risk of death.

“The cancer care community urgently needs data on the effects of COVID-19, specifically in patients with cancer,” ASCO President Dr. Howard A. Burris III said in a press release. “How we improve the care we provide these patients and reduce the number of deaths and severe consequences associated with this disease are among the top questions. The COVID-19 and Cancer Consortium registry is a great example of the community quickly coming together to identify and collect the data we need on a large scale.”

The COVID-19 & Cancer Consortium (CCC19), which was founded on March 15 and started receiving reports on March 17, helps researchers collect a large and more representative sample to learn more about COVID-19’s impact on cancer. The consortium consists of a survey that is designed for real-time reporting as well as after a course of COVID-19 is complete. Institutions from the United States and Canada have participated in the study, and anonymous reports have also been submitted by individuals in several other countries and regions.

This first analysis includes data from 928 cases of patients with cancer and COVID-19. Median age of the patients was 66 years. Of note, according to Warner, 30% of the patients were over the age of 75.

Half of the patients were white, 16% were black or African American and 16% were Hispanic. Less than half (39%) of the patients were on active treatment and 43% had active cancer.

Breast (21%), prostate (16%) and gastrointestinal (12%) cancer were the three most common types of cancer in the patient population.

More than half (52%) of the patients were never smokers, 37% were former smokers and only 5% were current smokers.

After a median follow-up of 21 days, 13% of the patients have died. Seventy patients aged older than 75 years have died, and 25 deaths have occurred in patients with progressing disease.

Although the follow-up time is rather short, lead study author Dr. Jeremy L. Warner, noted during a pre-recorded presentation that it reflects the urgency in which this data was needed.

Half of the patients were hospitalized, of whom 23% have died. The researchers also assessed outcomes in the 132 patients who were admitted to the ICU. Of those 132 patients, 38% died, and of those deaths, 54% occurred in patients older than 75.

Approximately 180 patients received a combination of hydroxychloroquine and azithromycin, and 90 patients received hydroxychloroquine alone. Of note, according to Warner, only two patients received the drugs as part of clinical trials. The rest received the drug off label.

“Since these drugs are generally available, that's at the discretion of the treating provider but it's still notable,” Warner, an associate professor of medicine and biomedical informatics at Vanderbilt University Medical Center, said during the press briefing. “There's a lot to learn in terms of what (the) characteristics of these patients are.”

Patients who were hospitalized, according to Warner, were more likely to receive hydroxychloroquine and azithromycin, although he did note that using hospitalization as a representation to determine how critical something is should be done with caution considering not every country has the same policies regarding hospitalizations.

Patients with cancer and COVID-19 who received hydroxychloroquine and azithromycin to treat the virus had an almost three-times greater risk of death than those who were in remission or had no evidence of active disease. However, as Warner noted, hydroxychloroquine alone was not a significant risk factor for death after adjusting for other factors.

“I will caution that these final results (are) of uncertain validity due to high risk of residual confounding, for example, patients receiving this combination were more likely to have severe disease or more likely to be hospitalized,” he said. “Overall, we need a larger sample size and longer follow-up to more completely understand the impact of COVID-19 on specific patient subsets, such as those with certain types of cancer and what happens over time beyond this short initial period.”

Warner continued, noting that prospective trials are needed to clarify if there is a benefit or risk associated with the drugs, whether alone or in combination.

“I think what we found is somewhat consistent with The Lancet article that was published last week based also on a retrospective analysis. Our dataset is somewhat perspective, some of the reports are retrospective. Even with the prospective reports, they are not being made by the treating provider.”

As a result, there is a possibility of a disconnect considering the researchers are unable to collect more information directly from the treating providers. And although there are daily reports coming in from the more than 100 participating institutions, the nature of the database, according to Warner, creates limitations.

“It is inherently limited, as any registry effort of this type will be limited, just by the fact that certain patients may be reported on preferentially to others,” he said.

However, as the database continues to grow, Warner assured that researchers will be able to answer their questions with more detail.