While radiation therapy is not currently used in combination with CDK4/6 inhibitors in clinical trial protocols, findings from this study support future consideration of this approach in clinical studies.
For patients with metastatic breast cancer, radiation therapy is a valuable treatment modality. Surprisingly, there is a scarcity of information and studies assessing the safety and feasibility of concomitant administration of radiation therapy and CDK4/6 inhibitors. During clinical trials, sufficient data were not gathered, and only small retrospective studies have begun to assess the feasibility of this treatment combination. Because hypothetical concerns about potentially augmenting toxicity or decreasing treatment effectiveness exist, it is imperative to expand on these preliminary findings.
Marcin Kubeczko, MD, and colleagues from the Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice, Poland, studied 116 patients with metastatic breast cancer who were being treated at their center with CDK4/6 inhibitors between 2018 and 2020. A total of 59 patients were being treated with ribociclib and 57 were treated with palbociclib. Of these patients, 26 were treated with radiation therapy and were included for further analysis, and concurrent radiation therapy was the treatment choice in 10 of 26 patients while sequential radiation therapy was the option chosen in 16 of 26 patients. The median patient age was 55 years (range, 23-78 years). Fifteen (57%) patients had been diagnosed with recurrent breast cancer, whereas 11 (42%) had been diagnosed with de novo metastatic breast cancer. Of the 16 patients who had received chemotherapy previously, 6 of them had received CDK4/6 inhibitor treatment within 1 year. In the first-line setting, 73% of patients received CDK4/6 inhibitor therapy. In the majority (N = 9; 35%) of patients, the main sites of metastasis were bones and the viscera. In the 26 patients treated with radiation therapy, 32 radiation therapy treatments were performed. An array of radiation treatment regimens were employed, including 20 Gy in 5 fractions (N = 9), 8 Gy in 1 fraction (N = 10), and 30 Gy in 10 fractions (N = 3). Palliative radiotherapy to the bones was administered to the majority of the patients; 6 (23%) of these patients received radiation therapy to the pelvic area.
Assessment showed that grade 2 and grade 3 neutropenia was experienced by 19 (73%) patients, with no cases of grade 4 neutropenia. Cases of grade ≥2 neutropenia were reported in 8 (50%) patients after sequential radiation therapy during the first cycle of CDK4/6 inhibitor treatment and occurred significantly more often in patients after simultaneously receiving radiation therapy (all treated, N = 10; P = .0095). After receiving sequential radiation therapy, no neutropenia was observed by 7 (27%) patients. CDK4/6 inhibitor dose reduction occurred in 4 (15%) patients; this was inclusive of 1 patient who was treated with concurrent radiation therapy and 3 sequential radiation therapy recipients. The cause of dose reduction in these 4 cases was prolonged grade 3 neutropenia.
Specific details of cases were described. The first patient was aged 60 years and received radiation therapy 8 Gy in 1 fraction for bone metastases in the lumbar region and the thoracic, spine, and rib regions. The second patient was aged 31 years and received radiation therapy 20 Gy in 5 fractions for the central nervous system, then 20 Gy in 5 fractions for bone metastases in the thoracic, lumbar, and sacral spine regions. All of these treatments were performed during 1 month prior to receiving the first dose of CDK4/6 inhibitor. The third and fourth patients were described as having received additional doxorubicin-based chemotherapy shortly before receiving CDK4/6 inhibitor treatment.
None of these patients discontinued treatment due to toxicity, at a median follow-up of 17 months (range, 9-20 months). One patient remained on ribociclib at a first dose reduction level. Two patients remained on ribociclib at a second dose reduction level. Lastly, 1 patient remained on ribociclib treatment for 11 consecutive months and then the CDK4/6 inhibitor treatment was ceased due to progression of the disease. In patients treated previously with chemotherapy (N = 16) and chemotherapy-naïve patients (N = 10; P = .6680), there was no difference in neutropenia rate detected. Cases of enhanced dermatologic toxicity and acute radiation-induced enterocolitis were not found. There were no observations of other serious adverse events.
Although radiation therapy did not change the treatment course in most patients and appeared well-tolerated in general, concurrent radiation therapy led to more frequent neutropenia than sequential therapy. Possible risk factors for radiation-induced reduction in CDK4/6 inhibitor dose might be extensive radiation fields and previous chemotherapy in a metastatic setting. Until now, combined radiation therapy is not a part of clinical trial protocols for adjuvant CDK4/6 inhibitors. Based on the findings of this study that suggest a favorable tolerability profile, assessing this combination may be warranted in future clinical trials.
Source: Kubeczko M, Badora-Rybicka A, Polakiewicz-Gilowska A, et al. Adverse events in breast cancer patients treated with concurrent or sequential radiation therapy and CDK 4/6 inhibitors in metastatic setting. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PS15-09.