Abstract PS15-09: Adverse events in breast cancer patients treated with concurrent or sequential radiation therapy and CDK 4/6 inhibitors in metastatic setting
Authors: Kubeczko Marcin , Badora-Rybicka Agnieszka , Polakiewicz-Gilowska Anna , Leśniak Aleksandra , Świderska Katarzyna , Mianowska-Malec Marta , Grandys Barbara , Łanoszka Barbara , Stankiewicz Magdalena , Gawkowska Marzena , Nowicka Elżbieta , Woźniak Grzegorz , Gabryś Dorota , Tarnawski Rafał , Miszczyk Leszek , Jarząb Michał 
Published: February 2021

Abstract
Background. Radiation therapy (RT) is important modality in MBC patients, however, there is paucity of data on safety and feasibility in combining radiation and a cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6i). No sufficient data were gathered in clinical trials and a few small retrospective series were published; it is important to extend these data. Theoretically, concerns pertain both the augmentation of effect (toxicity) or decrease of treatment effectiveness. Methods. 116 patients with MBC were treated in our center with CDK 4/6i (ribociclib n=59, palbociclib n=57) between 2018-2020. 26 patients were also treated with RT and were included into further analysis. 10 patients were treated with concurrent RT and 16 patients with sequential RT. Median age of patients was 55 years (range 23-78). 11 patients (42%) were diagnosed with de novo MBC, whereas 15 patients (57%) with recurrent breast cancer. 16 patients received prior chemotherapy, 6 of them less than 1 year before CDK 4/6i treatment. 73% of patients received CDK 4/6i in first line setting. Bones were the main metastatic site in the majority of patients, whereas visceral metastasis were diagnosed in 9 patients (35%). Overall 32 RT treatments in 26 patients were performed. Various RT regimens were used, including 8 Gy in 1 fraction (n=10), 20 Gy in 5 fractions (n=9), 30 Gy in 10 fractions (n=3). SBRT was performed in 5 patients and chest wall irradiation in 3 patients. The majority of patients received palliative radiotherapy to the bones, including 6 patients (23%) with RT to the pelvic area. Results. Nineteen patients (73%) experienced G2 and G3 neutropenia, with no G4 case. Neutropenia G≥2 occurred during first cycle of CDK 4/6i treatment in 50% of patients (n=8) after sequential RT and signicantly more often in patients after concurrent RT (all treated, n=10; p= 0.0095). No neutropenia was observed in 7 patients after sequential RT (27%). 4 patients (15%) had CDK 4/6i dose reduction, including 1 patient treated with concurrent RT and 3 patients treated with sequential RT. In all 4 patients the cause of dose reduction was prolonged G3 neutropenia. Patients were treated as follows: 60yo patient received RT 8 Gy in 1 fraction for bone metastases in lumbar and thoracic spine and ribs; 31yo patient received RT 20 Gy in 5 fractions for central nervous system, then 20 Gy in 5 fractions for bone metastases in thoracic, lumbar and sacral spine (all of these treatments were performed during 4 weeks before CDK 4/6i first dose). The following two patients received additionally doxorubicin-based chemotherapy shortly before CDK 4/6i treatment. At median follow up of 17 months (range 9-20 months) none of these patients discontinued treatment because of toxicity: one patient continue ribociclib at first dose reduction level, two patients continue ribociclib at second dose reduction level and one patient continued ribociclib treatment for 11 consecutive months and then CDK 4/6i treatment was ended because of disease progression. There was no difference in neutropenia rate in patients treated previously with chemotherapy (n=16) and chemo-naïve patients (n=10; p=0.6680). No cases of acute radiation-induced enterocolitis or enhanced dermatologic toxicity were found. No other serious adverse events were observed. Conclusions. We found that concurrent RT leads to more frequent neutropenia than sequential RT, although it did not change treatment course in the majority of patients and appeared well-tolerated. Potential risk factors for radiation-induced CDK4/6i dose reduction might be extensive radiation fields and previous chemotherapy in metastatic setting. Until now, combined RT is not a part of adjuvant CDK 4/6i clinical trials protocols. Excellent tolerance of this combination supports future consideration of this scenario in clinical trial setting.
Citation Format: Marcin Kubeczko, Agnieszka Badora-Rybicka, Anna Polakiewicz-Gilowska, Aleksandra Leśniak, Katarzyna Świderska, Marta Mianowska-Malec, Barbara Grandys, Barbara Łanoszka, Magdalena Stankiewicz, Marzena Gawkowska, Elżbieta Nowicka, Grzegorz Woźniak, Dorota Gabryś, Rafał Tarnawski, Leszek Miszczyk, Michał Jarząb. Adverse events in breast cancer patients treated with concurrent or sequential radiation therapy and CDK 4/6 inhibitors in metastatic setting [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-09.