Enhanced toxicity with CDK 4/6 inhibitors and palliative radiotherapy: Non-consecutive case series and review of the literature

5•CDK 4/6 inhibitors are commonly used in patients with advanced hormone receptor positive breast cancer.5•Many patients receive palliative radiotherapy for symptomatic disease concomitantly with a CDK 4/6 inhibitor.5•There is a paucity of data on the safety of combining a CDK 4/6 inhibitor with palliative radiotherapy.5•We report on 5 cases at our institution where enhanced radiotherapy toxicity was observed when RT was delivered during or prior to treatment with a CDK 4/6 inhibitor.5•We review pre-clinical and mechanistic data and hypothesise on possible mechanisms for this phenomenon. Current first-line systemic treatment in most patients with metastatic hormone receptor-positive, HER-2 negative breast cancer is an aromatase inhibitor in combination with a cyclin dependant kinase (CDK) 4/6 inhibitor. Frequently, these patients require palliative radiotherapy (RT) for symptomatic disease management. There is a paucity of data on the safety of combining a CDK 4/6 inhibitor with palliative RT, with conflicting case reports in the literature. We report on 5 cases at our institution where enhanced radiotherapy toxicity was observed when palliative doses of RT was delivered during or prior to treatment with a CDK 4/6 inhibitor. After review of pre-clinical and mechanistic data, we hypothesise that the effects of CDK4/6 inhibition on normal tissue and the tumour microenvironment may impede tissue recovery and exacerbate acute radiation and radiation recall toxicities. Further studies are required to clarify the potential toxicities of this combination. Clinicians should consider the potential risks when combining CDK 4/6 inhibitors with palliative RT and individualise patient management accordingly.