Findings from the UK Coronavirus Cancer Monitoring Project (UKCCMP) are indicative that COVID-19 mortality in patients with cancer is mainly driven by advanced age and comorbidities. The UKCCMP data so far do not generate evidence that cancer patients on cytotoxic chemotherapy or other anticancer treatments are at an increased risk of mortality from COVID-19 disease compared with those not on active treatment. The findings from the UK registry provide some confidence that delivery of effective anticancer treatments should continue during this difficult time. The findings are reported by UKCCMP team on 28 May 2020 in The Lancet.
The authors explained in background that to date no high-quality evidence exists to identify risks from use of recent anticancer treatments during the COVID-19 pandemic. It has been generally assumed that patients with cancer receiving systemic anticancer treatments are at a higher risk from the COVID-19 disease. However, the evidence is scarce and limited to retrospective series involving small numbers of patients, but such hypothesis has led to widespread global changes to patterns of prescribing chemotherapy and anticancer treatment.
The study team underlined that in a global health emergency, oncologists must secure evidence from a large dataset, which can then inform their risk-benefit analyses for individual patients in terms of the use of anticancer treatments. The UKCCMP database of UK COVID-19 patients with cancer was launched with the support of the UK oncology professional bodies, including the Association of Cancer Physicians, the Royal College of Radiologists, the National Oncology Trainees Research Collaborative for Healthcare Research, patient support groups including Macmillan Cancer Support, and charities including Action Radiotherapy.
The database was designed as a public health surveillance registry to support rapid clinical decision making, in accordance with the UK Policy Framework for Health and Social Care Research, the UK National Research Ethics Service, and the UK Governance Arrangement for Research Ethic Committees. At an institutional level, this cohort study was approved according to local information governance processes.
All patients with active cancer and presenting to the network of 55 cancer centres in UK from 18 March 2020 to 26 April 2020 with COVID-19 were eligible for enrolment into the UKCCMP. Eligible patients tested positive for severe acute respiratory syndrome coronavirus 2 on RT-PCR assay from a nose or throat swab. The study team excluded patients with a radiological or clinical diagnosis of COVID-19, without a positive RT-PCR test. The primary endpoint was all-cause mortality, or discharge from hospital, as assessed by the reporting sites during the patient hospital admission.
During reported period, the study team analysed 800 patients with a diagnosis of cancer and symptomatic COVID-19. In total, 412 (52%) patients had a mild COVID-19 disease course. The study team reported that 226 (28%) patients died and risk of death was significantly associated with advanced patient age, odds ratio 9.42 (95% confidence interval [CI] 6.56–10.02]; p < 0.0001), being male (1.67, CI 1.19–2.34), p = 0.003), and the presence of other comorbidities such as hypertension (1.95 CI 1.36–2.80, p < 0.001) and cardiovascular disease (2.32 CI 1.47–3.64).
In total, 281 (35%) patients had received cytotoxic chemotherapy within 4 weeks before testing positive for COVID-19. After adjusting for age, gender, and comorbidities, chemotherapy in the past 4 weeks had no significant effect on mortality from COVID-19 disease, when compared with patients with cancer who had not received recent chemotherapy (1.18 CI 0.81–1.72, p = 0.380). The study team found no significant effect on mortality for patients with immunotherapy, hormonal therapy, targeted therapy, radiotherapy use within the past 4 weeks.
The authors concluded that recent chemotherapy use in cancer patients before severe acute respiratory syndrome coronavirus 2 infection was not significantly associated with increased mortality. Although the numbers of patients are smaller, the study team did not observe any significant risk from recent use of immunotherapy, hormonal therapy, targeted therapy or radiotherapy.
The authors underlined also the UKCCMP limitations. In particular, the analysis is partly dependent on the UK national COVID-19 testing policy, which is less permissive than in other countries. It relies on RT-PCR, which has false-negative results. A selection bias might exist as patients might have stopped chemotherapy because of a poor performance status. However, the study team has addressed this limitation through multivariate analyses with age and comorbidity correction. The study team has not commented on overall incidence of COVID-19 positivity among cancer patients because they do not yet have secure numerators and denominators for that calculation, but they reported that the total number of cases remains low, probably reflecting physical distancing measures currently in place for cancer patients in hospitals.
Despite above described limitations, the UKCCMP covers most of the UK cancer population, with universal access to cancer care. It has been achieved through the rapid set up of a coordinated emergency cancer network. It is planned to continue with update of the UKCCMP registry data at weekly basis and share outcomes with oncology community.
The authors reported that with more patients analysed, they will be able to answer more questions and guide further research. In particular, future studies should investigate whether the grading of COVID-19 could be further refined to understand better the heterogeneity between different tumour subtypes, to clarify the risks of specific anticancer treatments, to discoverer whether risks related to timing of anticancer treatments exist, and to understand better interaction between the host immune response and risk from COVID-19.
Furthermore, the authors emphasised that interesting questions exist about differential effects of various anticancer treatments on different components of the immune system and how these factors will interplay with the risk of contracting SARS-CoV-2 infection, or with the possibility of severe COVID-19 disease sequelae such as the cytokine storm.
This project was funded by the University of Birmingham and the University of Oxford.
Lee LYW, Cazier JB, Starkey T, et al. COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. The Lancet; Published online 28 May 2020. DOI: https://doi.org/10.1016/S0140-6736(20)31173-9