No abstract

Purpose/Objective(s): There is a paucity in the literature regarding the concurrent use of cyclin-D kinase 4/6 (CDK 4/6) inhibitors with radiotherapy (RT). Given the well-established role of CDK4/6 inhibitors in metastatic breast cancer (both first and second line) the incidence of patients requiring palliative RT is likely to increase. Although there have been a few published case reports attributing excess toxicity to their concurrent administration, no national guidelines exist to guide best practice. Based on our experience, we set out to demonstrate that there is no enhanced toxicity of patients on CDK4/6 inhibitors receiving palliative RT. Materials/Methods: We performed a retrospective review of the electronic medical records system used at our institution, reviewing data from the time of CDK4/6 licensing in 2016 to 2019. We included all patients with metastatic breast cancer prescribed a CDK4/6 inhibitor (abemaciclib, ribociclib and palbociclib) at the time of and up to 28 days after the first dose of palliative RT between 2016-2019. We reviewed electronic record documentation of: length of RT course, dose and site. We recorded the full blood count levels preceding RT and 4 weeks after completion of RT. We reviewed toxicity in the form of neutropenia, fatigue, skin changes, nausea and pain as per CTCAEv5 and RTOG guidance. Results: Twenty-three (23) patients were identified, and 28 courses of RT were delivered. Timing of administration of CDK4/6 inhibitor varied from establishment 951 days before RT to commencement within 27 days of receiving RT. The majority of patients were prescribed palbociclib 87% (n Z 20), 8% abemaciclib (n Z 2) and 4% ribociclib (n Z 1). Patients received RT to spinal metastases (n Z 16 (57%)), long bones (n Z 11 (39%)) and brain (n Z 1 (4%)). Most patients received 8Gy/1 fraction (n Z 14(50%)), others received 20Gy/5 fractions (n Z 11 (39%)), 6Gy/1 fraction (n Z 2 (7%)) and 30Gy/10 fractions (n Z 1 (4%)). Toxicity of any CTCAE grade was seen in 46% of all cases; 7 (25%) patients who started CDK4/6 inhibitors after RT experienced toxicity vs 6 (21%) who started CDK4/6 inhibitors prior to RT. We identified heterogeneity in practice with some clinicians advising holding of the CDK4/6 during RT. Of the 6 patients who had documented advice to hold CDK4/6 inhibitors around time of RT delivery, 4 (67%) experienced toxicity (3x Grade 1, 1x Grade 2, 1x Grade 3). The patient with grade 3 skin toxicity started a CDK4/6 inhibitor 2 weeks after RT. This patient was immobile, contributing to skin breakdown. Conclusion: Based on our review of the published literature, we report on the largest cohort studied to date. We did not find evidence of worsening toxicity with concurrent CDK4/6 and palliative RT administration. Notably, no patients had to stop CDK4/6 inhibitors as a result of RT toxicity, and holding of CDK4/6 inhibitor did not reduce the risk of RT toxicity. We will be creating local guidelines to reflect our findings and recommend similar studies are replicated at other centers to allow...