Abstract PS11-20: Radiation therapy (RT) induced toxicity in advanced breast cancer (ABC) patients treated with CDK4/6 inhibitors (CDK4/6is)
Authors: Stjepanovic Neda , Thawer Alia , Nathoo Dilshad , Giffoni Danilo , Romero Maria , Lott Anthony , Eisen Andrea , Pezo Rossanna , Jerzak Katarzyna , Trudeau Maureen , Gandhi Sonal , Warner Ellen 
Published: February 2021

Abstract
Background: For patients with ABC being treated with CDK4/6is palliative (RT may still be necessary to metastatic sites that are symptomatic or at risk for complications. Although preclinical data suggests synergy between CDK4/6is and RT, clinical data regarding the safety of this combination are conflicting, with some reports of increased toxicity in the radiation field. Our aim was to review the practice regarding holding CDK4/6is during RT and subsequent clinical outcomes at the cancer centre with the largest volume of ABC patients in Canada. Methods: Chart review was completed for 313 ER positive and Her2 ABC pts treated with CDK4/6is at the Sunnybrook Health Sciences Centre from 2016 to 2020. All patients who received RT during the course of treatment with CDK4/6is were included in this analysis. Greater than expected toxicity events were defined as higher than grade 1 non-hematological toxicity as per Common Terminology Criteria for Adverse Events during RT or in the 30 days post RT. Descriptive statistics were used for demographics and treatment outcomes. Results: Fifty patients received RT to 74 different sites during treatment with CDK4/6is (46 palbociclib and 4 ribociclib). Median age was 56 (41-88) years. Most frequent RT sites were: bone (n=51), brain (n=7), lung (n=4), breast (n=4) and liver (n=3). CDK4/6is were held during RT of 55 sites (37 patients), starting a median of 7 (0-43) days prior to first fraction of RT and restarted a median of 7 (0-71) days after completing the RT. A CDK4/6i was administered concomitantly with RT to 19 sites (15 patients). No greater than expected toxicity was observed in patients for whom the CDK4/6i was held during RT. Among patients who received concomitant treatment, we observed 4 non-hematological adverse events (21%) in organs included in the field of radiation. In combination with palbociclib we observed grade 3 colitis after 30 Gy to hip/pelvis bones, grade 2 esophagitis after 30 Gy to C1-C4 vertebrae and grade 2 enteritis after 30 Gy to the upper femur. In combination with ribociclib one patient developed grade 3 hepatitis after 20Gy to T10-L2 vertebrae. Conclusions: This retrospective observational study of 50 patients with advanced ER positive Her2 negative BC treated with CDK4/6is who received palliative RT demonstrated a high rate of radiation toxicity (21%) in those patients for whom the CDK4/6i was given concurrently. Quality improvement work in this area, including practice guidelines, is warranted.
Citation Format: Neda Stjepanovic, Alia Thawer, Dilshad Nathoo, Danilo Giffoni, Maria Romero, Anthony Lott, Andrea Eisen, Rossanna Pezo, Katarzyna Jerzak, Maureen Trudeau, Sonal Gandhi, Ellen Warner. Radiation therapy (RT) induced toxicity in advanced breast cancer (ABC) patients treated with CDK4/6 inhibitors (CDK4/6is) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-20.