Safety of palbociclib concurrent with palliative pelvic radiotherapy: discussion of a case of increased toxicity and brief review of literature.

Several cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are indicated in the treatment of metastatic hormone receptor-positive (HR)/ human epidermal growth factor receptor 2 (HER2) negative breast cancer which includes palbociclib, ribociclib and abemaciclib. Pelvic radiation therapy (RT) is often indicated for symptomatic or progressive bone metastasis. There are limited data on concurrent use of CDK4/6 inhibitors with pelvic RT with few retrospective studies in the literature involving a small number of patients. The major side effects of these agents include haematological toxicities, while non-haematological toxicities are less severe. There are concerns for an increased possibility of synergistic toxicity with concurrent use of CDK4/6 inhibitors with pelvic RT. Here we describe an instance of acute grade 3 gastrointestinal toxicity and discuss the relevant literature. A 77-year-old lady treated with palliative conventional RT 30 Gy/ 10 fractions concurrently with palbociclib to left hemipelvis and proximal femur, developed severe pancolitis starting 5 days from last RT. She needed inpatient care for 3 weeks and recovered with mesalamine and supportive care. We also postulate a few strategies that can be adopted in patients receiving palliative RT in such a scenario. The agents should be stopped 1 week before, during and for a time (1 week minimally) after RT. A shorter course of 5 fractions (and ablative RT as indicated) can be considered to minimise treatment gaps. Highly conformal techniques (intensity-modulated radiotherapy/ volumetric-modulated arc therapy) can significantly reduce bowel dose and should be considered in patients with pre-existing GI comorbidities or prior GI toxicity with these agents.