Abstract PD8-12: Safety and efficacy of palbociclib and radiotherapy in metastatic breast cancer patients: Initial results of a novel combination
Authors: Chowdhary M , Sen N , Chowdhary A , Usha L , Cobleigh M , Patel KR , Wang D , Barry PN , Rao RD 
Published: May 2019

Abstract
Purpose: Palbociclib is a selective CDK4/6 inhibitor approved for the treatment of metastatic ER+/HER2- breast cancer. Inhibition of CDK4/6 prevents cell cycle progression from G1 to the more radioresistant S phase, raising the possibility of an enhanced therapeutic effect if combined with radiotherapy (RT). Despite this potential benefit, clinicians seldom use this combination due to fear that RT may exacerbate palbociclib toxicity, particularly leukopenia. Our aim is to report the preliminary results of patients with metastatic breast cancer who received RT while receiving palbociclib.
Methods: We retrospectively reviewed records of all patients who were treated with palbociclib at our institution from 2015-2018. Patients who received RT for symptomatic metastases concurrently or within 14 days of last drug administration were included in our analysis. Local treatment effect was assessed by clinical exam and subsequent CT or MRI imaging, if applicable. Toxicity was graded based on CTCAE v5.0.
Results: A total of 16 females received palliative RT in association with palbociclib. The median age of the treated patients was 59.6 (range 33.3-91.0) years. The median time of closest palbociclib use to RT administration was 5 (range 0-14) days.
The following sites were treated in order of frequency: bone (10-axial skeleton [8-vertebra]; 1-ilium), brain (4: 3-WBRT & 1-SRS), and mediastinum (1). RT dose/fractionation for bone was 30 Gy/10 fxn (7), 35 Gy/14 fxn (2), 37.5 Gy/15 fxn (1), and 18 Gy/1 fxn (1). WBRT dose/fractionation was 30 Gy/10 fxn for all patients. SRS brain dose was 25 Gy/5 fxn. The patient treated to the mediastinum received 36 Gy/18 fxn.
At most recent follow-up, 12 patients are still living. The median time from RT to last known follow-up or death is 10.3 (range 1.7-29.6) months. Pain relief was achieved in 15 of 16 (93.8%) patients. No radiographic local failure was noted in the 13 patients with evaluable follow-up imaging.
The combination of RT and palbociclib was well-tolerated. Grade 1 fatigue, dermatitis, and nausea was noted in 5, 3, and 1 patient, respectively. One patient with WBRT developed Grade 1 headache. Six of 16 patients were leukopenic prior to RT initiation. Following RT, 7 patients were observed to have a drop in WBC count, of which 2 dropped into the leukopenic range. Only a total of 5 patients were leukopenic following RT, of which 3 were leukopenic before receiving RT. No acute or late Grade 2 or higher cutaneous, neurological, gastrointestinal, or hematologic toxicities were noted.
Conclusions: The use of RT in patients receiving palbociclib resulted in minimal Grade 1 and no Grade 2+ toxicities, including leukopenia. This treatment can be used safely in symptomatic patients without discontinuation of systemic therapy. Further larger prospective studies with longer follow-up are needed to confirm these results.
Citation Format: Chowdhary M, Sen N, Chowdhary A, Usha L, Cobleigh M, Patel KR, Wang D, Barry PN, Rao RD. Safety and efficacy of palbociclib and radiotherapy in metastatic breast cancer patients: Initial results of a novel combination [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD8-12.