Effect of Concomitant Treatment with Radiation Therapy and CDK4/6 in Patients with Advanced Breast Cancer

In this study, a high rate of radiation toxicity was observed in patients with advanced breast cancer treated with CDK4/6 inhibitors.

A synergistic effect between CDK4/6 inhibitor therapy and radiation therapy has been implied based on preclinical data, yet clinical data have been mixed, with conflicting reports about the safety of this combination and preliminary reports suggesting increased toxicity in the radiation field. Neda Stjepanovic, MD, MsSci, Medical Oncologist, Cancer Genetics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, and colleagues reviewed their clinical practice experience with CDK4/6 inhibitors and radiation therapy and subsequent clinical outcomes. This center has the largest volume of patients with advanced breast cancer in Canada, allowing for a comprehensive study.

Based on chart review, a total of 313 patients with estrogen receptor–positive and HER2-negative advanced breast cancer were treated with CDK4/6 inhibitors at the Sunnybrook Health Sciences Centre during a 4-year time span beginning in 2016.

Included in the analysis were all patients who received radiation therapy while receiving treatment with CDK4/6 inhibitors. For the study, greater than expected toxicity events were defined as higher than grade 1 nonhematologic toxicity in accordance with Common Terminology Criteria for Adverse Events during radiation therapy or in the 30 days following radiation therapy.

In 50 patients receiving CDK4/6 inhibitors (46 receiving palbociclib and 4 receiving ribociclib), radiation therapy was administered to 74 different sites during treatment. Median age was 56 years, with a range of 41 to 88 years.

Bone (N = 51), brain (N = 7), breast (N = 4), liver (N = 3), and lung (N = 4) were the most frequent sites where radiation therapy was administered.

Thirty-seven patients receiving radiation therapy of 55 sites were treated concurrently with CDK4/6 inhibitors, which began a median of 7 days (range, 0-43 days) prior to first fraction of radiation therapy and restarted a median of 7 days (range, 0-71 days) after completing the radiation therapy. CDK4/6 inhibitors were administered concomitantly to 15 patients receiving radiation therapy in 19 sites.

When CDK4/6 inhibitor therapy was held during radiation therapy, observed toxicity was not greater than expected. Four nonhematologic adverse events were recorded among the patients who received concomitant treatment; 21% of these events occurred within the field of radiation organ.

When combined with ribociclib, after 20 Gy radiation to T10-L2 vertebrae, 1 patient developed grade 3 hepatitis. In patients who received palbociclib and radiation therapy, investigators reported observing the following after 30 Gy radiation to the target site: grade 3 colitis when the hip/pelvis bones were targeted, grade 2 esophagitis when C1-C4 vertebrae were targeted, and grade 2 enteritis after the upper femur was targeted.

The investigators concluded that their study of 50 patients with advanced estrogen receptor–positive, HER2-negative breast cancer treated with CDK4/6 inhibitors and palliative radiation therapy revealed a high rate of radiation toxicity (21%) in patients for whom the CDK4/6 inhibitor was given concurrently.

These results indicate that updated clinical practice guidelines and quality improvement work is merited and may improve outcomes.

Source: Stjepanovic N, Thawer A, Nathoo D, et al. Radiation therapy (RT) induced toxicity in advanced breast cancer (ABC) patients treated with CDK4/6 inhibitors (CDK4/6is). Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PS11-20.