Consequences of stopping a 4/6 cyclin D-dependent kinase Inhibitor in metastatic breast cancer patients with clinical benefit on endocrine treatment, in the context of the COVID-19 outbreak

ABSTRACT

Background: The impact of some medical decisions hurriedly taken during the COVID-19 first wave remains unknown. We tried to assess the consequences of one of these precautionary measures, namely the interruption of a 4/6 cyclin D-dependent kinase inhibitor (CDK4/6i) in metastatic patients with clinical benefit (complete response/partial response and patients with stable disease for at least 6 months) on endocrine treatment (ET). The main reason for this interruption was to limit the risk of myelosuppression (assumed as a serious risk factor for COVID-19) and other adverse effects that could overlap with symptoms and clinical signs described in the SARS-CoV-2 infection. Methods: We included 60 patients (median age 64 years old) in whom the CDK4/6i was stopped during the first COVID-19 outbreak. It was a non-interventional, retrospective, multicentric study. A univariate analysis was performed to assess risk factors associated with disease progression odds ratios (OR) were estimated along with their confidence intervals (CI). Key patient characteristics, all included in the statistical model, are presented in Table 1. Results: The average duration of a CDK4/6i interruption was 8 weeks. During this therapeutic break, 22 (37 %) patients Shad a radiological and/or clinical progression of the disease. Among them, CDK4/6i were taken back for the majority of patients (n=16/22;73 %) when the sanitary situation improved.For four patients (n=4/22;18 %), a new specific treatment (chemotherapy or targeted therapy) was initiated for rapid or symptomatic tumor progression. Two patients died while CDK4/6i was withdrawn. All the results of the univariate analysis are summarized in Table 2. During the CDK4/6i discontinuation, the risk of disease progression was significantly increased in the presence of liver metastases. This was the only variable with a significant effect in univariate analysis. Although not statistically significant, the risk of disease progression was higher when CDK4/6i withdrawal was longer, when patients had a more aggressive breast cancer (Luminal B) and when the tumor was considered as resistant to ET. Conclusions: The importance of maintaining the cell cycle inhibitor in addition to ET does not seem to be debatable as 36 % of patients progressed during CDK4/6i withdrawal. This is important in clinical practice when the question of CDK4/6i discontinuation arises for other reasons (analgesic radiotherapy or programmed surgery for example). Special attention should be paid to patients with liver metastases for whom stopping such a treatment seems to accelerate the natural course of the disease.