Impact of metastases directed radiation therapy on CDK4/6 inhibitors dose reduction and treatment discontinuation for metastatic HR+/HER2- breast cancer (MBC).

Abstract

562 Background: Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) represent the standard I-II line for hormonal receptors positive/human epidermal growth factor receptor 2 negative metastatic breast cancer (MBC) patients. Metastases directed radiotherapy (RT) for these patients is commonly used with palliative or radical schedules during systemic treatment. Although encouraging preliminary results were published, there is still a lack of robust data on the safety concerning RT during CDK4/6i treatment. Methods: we analyzed at Our Institution 85 consecutive patients treated in I (n=47) and II line (n=38) for MBC with CDK4/6i between April 2017 and September 2019 (22 ribociclib, 63 palbociclib). Overall, 25 (29.4%) patients received metastases directed RT during CDK4/6i treatment, including 14 concomitant (16.5%) and 11 sequential (12.9%). Estimated CDK4/6i half-life is 26 and 30 hours for palbociclib and ribociclib, respectively. Five half-lives are required to reduce drug concentration by 95-97%; thus, we also analyzed CDK4/6i treatment as non-concomitant or sequential to RT. Main endpoints of our analysis were impact of RT on CDK4/6i dose reduction and discontinuation, overall adverse events rate (any grade and grade ≥2), and neutropenia grade ≥2 as per CTCAE scale version 5.0. Results: at a median follow up of 12 months (range 3-29), we observed a CDK4/6i dose reduction in 35 patients (41.2%) and 5 patients (5.9%) discontinued treatment due to adverse events; 82 patients (96.5%) experienced any grade of toxicity, 72 (84.7%) a grade ≥2 and 70 patients (82.4%) neutropenia grade ≥2. We did not observe significant difference in terms of CDK4/6i dose reduction or discontinuation, any grade or grade ≥2 toxicity, neutropenia grade ≥2 in the comparison between patients receiving RT versus no RT and between patients receiving concomitant RT versus sequential RT versus no-RT (Table). Conclusions: our results showed that the prescription of a metastases directed RT during treatment with a CDK4/6i as I-II line for MBC did not significantly impact on dose reduction or discontinuation caused by an exceeding in adverse event rate. Although these promising results, caution should be used and cooperative initiatives strongly encouraged. [Table: see text]