Unexpected toxicity of CDK4/6 inhibitor palbociclib and radiotherapy

Abstract

Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors have recently been approved for the treatment of hormone receptor-positive and HER2-negative metastatic breast cancer in association with endocrine therapy in postmenopausal women.Data on the interaction of CDK4/6 inhibition and radiotherapy are scarce, but some studies show unexpected toxicity.Cases: We report three cases of unexpected severe or prolonged soft tissue, skin, and gastrointestinal toxicity in patients treated with a combination of radiotherapy and the CDK4/6 inhibitor palbociclib. Conclusion:These cases indicate a possible interaction between radiotherapy and palbociclib. Therefore, we recommend using radiotherapy cautiously when combined with CDK4/6 inhibitors.

Safety of CDK4/6 Inhibitors Combined with Radiotherapy in Patients with Metastatic Breast Cancer: A Review of the Literature

“…Colitis was reported in four patients, with two cases reported by Dasgputa et al [ 24 ] and Kawamoto et al [ 30 ] and the others documented by van Aken et al [ 28 ] and Guerini et al [ 16 ]. All colitis cases were classified as having grade 3 toxicity, in the context of palbociclib given in conjunction with 3D conformal RT to pelvic bones.…”

“…Based on the analysis of the 19 selected articles, 373 patients who received radiotherapy combined with CDK4/6 inhibitors were evaluated across 9 retrospective studies [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ], 4 case reports [ 22 , 23 , 24 , 25 ], 3 case series [ 26 , 27 , 28 ], and 3 letters to the editor [ 29 , 30 , 31 ], as shown in Table 1 .…”

“…Palbociclib was notably the most prescribed drug, followed by ribociclib and abemaciclib. There were 10 publications [ 17 , 18 , 19 , 22 , 24 , 25 , 26 , 28 , 29 , 30 ] describing patients who received exclusively palbociclib and 7 publications [ 13 , 14 , 15 , 16 , 20 , 21 , 31 ] that included the three drugs, but of these; palbociclib was also the most prevalent administered drug. In exceptions to this, Meattini [ 27 ] and Erjan [ 23 ] presented data on patients who received only ribociclib, with the first describing five cases and the second reporting a case.…”

“…Based on the analysis of the 19 selected articles, 373 patients who received radiotherapy combined with CDK4/6 inhibitors were evaluated across 9 retrospective studies [13][14][15][16][17][18][19][20][21], 4 case reports [22][23][24][25], 3 case series [26][27][28], and 3 letters to the editor [29][30][31], as shown in Table 1. Data on each study were gathered as follows: name of the principal author, year of publication, study design, number of patients available for analysis, median age at RT treatment, number of RT courses, RT technique, RT dose/fractionation, RT target, CDK4/6 inhibitor used, hormonal therapy given at the time of RT, timing of RT in relation to CDK4/6i, toxicities, and individual patient data when available.…”

“…Based on the analysis of the 19 selected articles, 373 patients who received radiotherapy combined with CDK4/6 inhibitors were evaluated across 9 retrospective studies [13][14][15][16][17][18][19][20][21], 4 case reports [22][23][24][25], 3 case series [26][27][28], and 3 letters to the editor [29][30][31], as shown in Table 1. Ribociclib ( 8) Fulvestrant/ leuprolide (28) Bone-other (61) IMRT ( 18)…”