Abstract PO-020: Impact of CDK 4/6i withdrawal or dose adjustment on COVID-19 incidence in HR+/HER2- mBC patients during the pandemic
Authors: Tolosa Pablo , Sanchez-Torre Ana , de Cabo Helena Bote , Sánchez-Bayona Rodrigo , Herrera Mercedes , Yarza Ramón , Lema Laura , Manso Luis , Ciruelos Eva 
Published: December 2020

Abstract
Background: On January 30th, 2020, the World Health Organization (WHO) declared public health emergencies of international 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) in combination 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 frequent toxicity 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 with ER+/HER2- mBC were on CDK4/6i treatment at that time. At the physicians’ discretion CDK4/6i withdrawal or dose adjustment was performed (considering age, comorbidities, and presence of previous neutropenia). The presence of risk factors such as advanced age or previous neutropenia were key issues when deciding to withdraw or adjust CDK4/6i. We conducted a retrospective analysis to evaluate this decision. All P were selected, and data were collected on May 15th, 2020. The main end point was to evaluate the impact of CDK4/6i withdrawal or dose adjustment (non-exposed) on the incidence of COVID-19 defined as high clinical suspicion (including anosmia) or positive 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 multivariate analysis.
Results: A total of 78 P were evaluated, 44 P treated with palbociclib, 21 with ribociclib, and 13 with abemaciclib in combination with hormonal therapies. Incidence of COVID-19 was 7.7% (6/78 P), 12.8% (5/39) in exposed P, and 2.7% (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 65 years and bone-only disease were associated with a lower COVID 19 relative risk, while diabetes mellitus was associated with a higher incidence. None of the 25 patients over age 70 were infected. In multivariate analysis the adjusted 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 was observed 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 the incidence of COVID-19. Greater collection of data during COVID-19 pandemic is needed and will provide us with strong evidence to make decisions in case of new outbreaks.
Citation Format: Pablo Tolosa, Ana Sanchez-Torre, Helena Bote de Cabo, Rodrigo Sánchez-Bayona, Mercedes Herrera, Ramón Yarza, Laura Lema, Luis Manso, Eva Ciruelos. Impact of CDK 4/6i withdrawal or dose adjustment on COVID-19 incidence in HR+/HER2- mBC patients during the pandemic [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-020.