258 - Acute Toxicity in SWOG 1706, a Randomized Trial Comparing Radiotherapy for Inflammatory Breast Cancer with and without Concurrent Olaparib
Presenter(s)
R. Jagsi1, A. Meisner2, P. Chalasani3, W. Barlow4, J. R. Bellon5, N. L. Henry6, D. Lew2, M. M. Matuszak1, J. M. Moran7, L. J. Pierce1, E. Rakovitch8, S. Reyes9, C. Speers10, J. Unger2, J. R. White11, W. A. Woodward12, R. C. Zellars13, L. Pusztai14, and P. Sharma15; 1Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 2Fred Hutchinson Cancer Center, Seattle, WA, 3George Washington University, Washington, DC, DC, 4Cancer Research and Biostatistics, Seattle, WA, 5Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, 6University of Michigan, Ann Arbor, MI, 7Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, 8Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 9St. Joseph’s Candler, Savannah, GA, 10University of Alabama-Birmingham, Department of Radiation Oncology,, Birmingham, AL, 11The Ohio State University Wexner Medical Center, Columbus, OH, 12The University of Texas MD Anderson Cancer Center, Houston, TX, 13Indiana University Department of Radiation Oncology, Indianapolis, IN, 14Yale, New Haven, CT, 15Division of Medical Oncology, The University of Kansas Medical Center, Kansas City, KS
Purpose/Objective(s): To evaluate tolerability of combining PARP-inhibitors with breast radiotherapy (RT) given divergent findings from prior studies.
Materials/Methods: From 05/19 to 06/24, we enrolled patients (pts) with inflammatory (T4d) non-metastatic (M0) breast cancer to a Phase 2 NCI cooperative group trial. After standard neoadjuvant systemic therapy and modified radical mastectomy, pts were randomized to RT+Olaparib or RT alone. The control arm was assigned 50 Gy of chest wall and nodal radiotherapy, including bolus, plus 10 Gy boost. The intervention arm was assigned the same RT regimen with 25 mg of olaparib bid daily during RT, intended for radiosensitization. Adverse events (AEs) were assessed using the CTCAE v5.0. This analysis explores the distribution of radiation dermatitis, all acute toxicity in the breast region (including skin and subcutaneous tissue AEs, folliculitis, skin infection, “injury/poisoning” AEs including RT dermatitis and wound complications, and breast or chest wall pain), and other AEs during RT by study arm, where the AEs were deemed possibly, probably, or definitely treatment-related. Chi-squared tests were used to compare proportions.
Results: Among 146 evaluable participants (73 control, 73 intervention), median age was 54.1. Grade 3+ radiation dermatitis was reported in 24.7% of patients in the intervention arm and 5.5% in the control arm (p=0.003). When considering all acute breast AEs, 24.7% had grade 3+ acute breast toxicity in the intervention arm vs 6.8% in the control arm (p=0.006). Acute breast AEs of any grade in the intervention arm included skin and subcutaneous tissue AEs in 43.8% (47.9% in controls), folliculitis in 1.4% (0% in controls), skin infection in 1.4% (0% in controls), “injury/poisoning” AEs in 71.2% (80.8% in controls), and breast or chest wall pain in 30.1% (32.9% in controls). One pt on the intervention arm (later noted to have a MUTYH mutation) had early, dense, confluent telangectasia throughout the 50 Gy fields with radiation induced lichenoid dermatitis. Intervention arm patients were more likely to experience any grade of GI toxicity (45.2% vs 26.0%, p=0.025) and laboratory investigation abnormalities (19.2% vs 0%, p<0.001).
Conclusion: Consistent with American trials of veliparib and rucaparib, and contrasting with a French trial of olaparib that used considerably higher doses of olaparib (up to 200 mg bid) with different RT techniques and had only 8.3% acute radiation dermatitis, this study, limited to inflammatory disease, suggests a clinically relevant increase in toxicity with concurrent administration of breast and nodal RT with bolus and boost even with low dose olaparib (25 mg bid). As PARP inhibitors become more commonly used, caution is appropriate, particularly if considering concurrent administration during breast radiotherapy outside of the investigational context.