ABSTRACT
Background: On January 30th, 2020, the World Health Organization (WHO) declared public health emergencies ofinternational concern (PHEIC) because of the outbreak of SARS-CoV2 and coronavirus disease 2019 (COVID-19).It has rapidly expanded all around the world, highlighting Madrid as one of the cities with a highest incidence.Oncologists have had to adapt treatments in order to reduce the pandemic impact. CDK4/6 inhibitors (CDK4/6i) incombination with hormone therapy are the standard of care in hormone receptor-positive (HR+), HER2-negative(HER2-) metastatic breast cancer (mBC) patients (P). Asymptomatic neutrophil count decrease is the most frequenttoxicity of these agents and may negatively impact on incidence and severity of COVID-19 disease. Methods: Hospitalized P increased exponentially from 10 to 16 March 2020 in our hospital. 78 P diagnosed withER+/HER2- mBC were on CDK4/6i treatment at that time. At the physicians' discretion CDK4/6i withdrawal or doseadjustment was performed (considering age, comorbidities, and presence of previous neutropenia). The presence ofrisk factors such as advanced age or previous neutropenia were key issues when deciding to withdraw or adjustCDK4/6i. We conducted a retrospective analysis to evaluate this decision. All P were selected, and data werecollected on May 15th, 2020. The main end point was to evaluate the impact of CDK4/6i withdrawal or doseadjustment (non-exposed) on the incidence of COVID-19 defined as high clinical suspicion (including anosmia) orpositive PCR;we estimate the odds ratio (OR) through logistic regression. As secondary objectives P characteristics were evaluated to identify and control potential confounding factors, we also calculate adjusted OR by multivariateanalysis. Results: A total of 78 P were evaluated, 44 P treated with palbociclib, 21 with ribociclib, and 13 with abemaciclib incombination with hormonal therapies. Incidence of COVID-19 was 7.7% (6/78 P), 12.8% (5/39) in exposed P, and2.7% (1/39) in non-exposed P. The OR for exposed patients was 5.8 IC 95% (0.62 to 50.25) p 0,077. Age over 65years and bone-only disease were associated with a lower COVID 19 relative risk, while diabetes mellitus wasassociated with a higher incidence. None of the 25 patients over age 70 were infected. In multivariate analysis theadjusted OR for exposed P was 7.68 (p 0.24). Incidence of COVID-19 was numerically higher in patients treated with ribociclib (14.29%) compared to palbociclib (4.55%) or abemaciclib (7.69%). No risk of progression disease wasobserved in P who had CDK 4/6i withdrawn or dose reduction (p 0.98). Conclusions: Despite the lack of statistical significance, CDK4/6i withdrawn or dose reduction may reduce theincidence of COVID-19. Greater collection of data during COVID-19 pandemic is needed and will provide us withstrong evidence to make decisions in case of new outbreaks.