1037 - ctDNA Predicts Pain Response in a Multi-Institutional Phase II Trial of Palliative Radiation, Palbociclib and Hormone Therapy in Metastatic Breast Cancer

M. Torres¹, S. Friend², A. Niemierko³, J. Y. Lin¹, A. Iafrate³, C. Xiao⁴, S. T. Kahn⁵, K. D. Godette⁶, S. Hanasoge⁵, D. S. Yu⁷, T. Y. Eng⁵, M. D. Cheney⁸, N. Wiggers⁹, A. Pippas¹⁰, K. Goginini², J. Meisel¹¹, D. M. Schuster¹², A. Bardia¹³, A. H. Miller¹⁴, J. Felger², J. Switchenko¹⁵, A. Zelnak¹⁶, K. Kalinsky¹⁷, T. Daniels², A. Medford³, and M. Bhave¹⁸; ¹Glenn Family Breast Center, Winship Cancer Institute, Emory University, Atlanta, GA, ²Emory University School of Medicine, Atlanta, GA, ³Massachusetts General Hospital, Boston, MA, ⁴Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, ⁵Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, ⁶Winship Cancer Institute, Department of Radiation Oncology, Emory University, Atlanta, GA, ⁷Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, ⁸Spectrum Healthcare Partners, Portland, ME, ⁹Northside Hospital, Atlanta, GA, ¹⁰John B. Amos Cancer Center, Piedmont Columbus Regional, Columbus, GA, ¹¹Department of Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, ¹²Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, ¹³UCLA, Los Angeles, CA, ¹⁴Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, ¹⁵Emory University, Atlanta, GA, ¹⁶Atlanta Cancer Care, Northside Hospital, Atlanta, GA, ¹⁷Emory Winship Cancer Institute, Atlanta, GA, ¹⁸Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA

Purpose/Objective(s): Studies examining ctDNA, a blood-based marker of tumor burden, have largely focused on its use as a prognostic and predictive biomarker. While patient reported outcomes are most often associated with treatment-related toxicities, tumor burden may also contribute to these symptoms, including pain. Approximately one third of patients (pts) who receive radiation (RT) to painful bone metastases (mets) do not experience pain relief, but few studies have identified predictors of response to palliative RT. We hypothesize that ctDNA will predict persistent pain in pts with metastatic breast cancer and could be used to predict response to palliative RT. Materials/

Methods: Plasma was collected before and 3 months (mos) after RT in pts with stage IV HR+, HER2- breast cancer in the context of a multi-institutional Phase II study of palbociclib, hormone therapy (HT), and palliative RT [30 Gy in 10 fractions (fxns) or 20 Gy in 5 fxns] for bone mets. ctDNA was detected using Snapshot, an anchored multiplex assay that detects 28 clinically significant cancer genes. Pts were eligible if treated with HT and palbociclib for at least one cycle and had either painful bone mets or asymptomatic bone mets at risk for a clinical event. Response, the primary endpoint, was prespecified as either a 2-point decrease in maximum pain score on the Brief Pain Inventory in the irradiated site(s) 3 mos post RT or prevention of a clinical event (e.g., cord compression) among pts with asymptomatic disease. The relationship between ctDNA and response to palliative RT was examined.
Results: 35 pts completed baseline and 3-month post RT assessments. 27 were treated for painful bone mets. With concurrent palbociclib, 61% and 37% of pts received aromatase inhibitors and fulvestrant, respectively. Median age was 60 years (31-83). 25% of pts were non-Hispanic Black. 72% of pts received 5 fxn RT and 69% received RT to one bone region. 29 pts (83%) were responders [95% CI: 66%-93%, p=.003]. Median progression free survival (PFS) was 30.4 mos (1.3 - 44.0). Three-year PFS and overall survival were 45.6% and 67.2%, respectively. 41% and 39% of pts had detectable ctDNA prior to and 3 mos post RT, respectively. 39% of pts had stable or increased ctDNA proportions 3 mos post RT relative to baseline. Six pts, all of whom presented with painful bone mets, did not respond to palliative RT. 100% of pts (n=15) without detectable ctDNA before and after RT responded to palliative RT, while 39% of pts with stable or increased ctDNA 3 mos post RT had no pain relief to RT (p=0.005). Four pts with ctDNA at baseline had no detectable ctDNA after RT, and all responded to RT.
Conclusion: Our multi-institutional Phase II trial is the first to demonstrate high rates of response to concurrent RT with palbociclib and HT and to evaluate ctDNA as a biomarker of pain and response to palliative RT in pts with metastatic breast cancer. Our novel findings indicate that ctDNA detection correlates with persistent pain, a patient reported symptom, and predicts the efficacy of palliative RT.